Antisense oligomers for treatment of centronuclear myopathies

Abstract

Provided herein are oligonucleotides / oligomers, peptide-oligonucleotide-conjugates, and targeting sequences complementary to a target region within a pre-mRNA of the human dynamin 2 (DNM2) gene. Also provided herein are methods of treating a disease or disorder associated with aberrant expression of DNM2 in a subject in need thereof, comprising administering to the subject the antisense oligomer, or a pharmaceutically acceptable salt thereof, or pharmaceutical composition comprising the antisense oligomer, or a pharmaceutically acceptable salt thereof.

Description

ANTISENSE OLIGOMERS FOR TREATMENT OF CENTRONUCLEAR MYOPATHIES RELATED APPLICATIONS

[0001] This application claims priority to U.S. Provisional Application No.: 63 / 591,174 filed on October 18, 2023, the contents of which are incorporated in their entirety. SEQUENCE LISTING

[0002] This application contains a Sequence Listing in computer readable format. The Sequence Listing is provided as a file entitled 4140_107PC01_Sequencelisting_ST2, created October 18, 2024 which is 360,337 bytes in size. The information in the computer readable format of the Sequence Listing is incorporated herein by reference in its entirety. BACKGROUND

[0003] Dynamin 2 is a ubiquitously expressed protein that belongs to the superfamily of large GTPases. Dynamin 2 (DNM2) acts as a mechanochemical scaffolding molecule that deforms biological membranes leading to the release of nascent vesicles. At the plasma membrane DNM2 is involved in clathrin-dependent and clathrin-independent endocytosis. This protein is also involved in the formation of vesicles from endosomes and trans-Golgi network. Several studies have highlighted the role of Dynamin 2 as regulator of actin and microtubule cytoskeletons.

[0004] Several dominant genetic diseases are caused by heterozygous mutations of the DNM2 gene coding for the dynamin 2 protein. Autosomal dominant centronuclear myopathy (AD-CNM) results from mutations in the DNM2 gene. AD-CNM is a rare congenital myopathy characterized by the high incidence of centrally placed nuclei in muscle fibers in absence of regenerative process. The AD-CNM is associated with a wide clinical spectrum from severe-neonatal to mild- adult forms. In general, motor milestones are delayed, and diffuse skeletal muscle weakness mainly involves facial and limb muscles. Muscle weakness is slowly progressive, but loss of independent ambulation may occur during the fifth decade. In the severe and early-onset CNM, pediatric patients usually have generalized weakness, hypotonia, moderate degree of facial weakness with open mouth, ptosis and ophthalmoplegia. No curative treatment is available for AD-CNM.

[0005] Mutations in the DNM2 gene are also involved in rare cases of Charcot-Marie-Tooth disease and Hereditary Spastic Paraplegia. Charcot-Marie-Tooth disease (CMT) is a hereditary motor and sensory neuropathy characterized by progressive loss of muscle tissue and touch sensation across various parts of the body. Hereditary spastic paraplegia (HSP) is an inheriteddisease characterized by lower extremity spasticity and weakness occurring in variable proportion.

[0006] About thirty heterozygous mutations in the DNM2 gene were identified as involved in AD- CNM, CMT, or HSP diseases, for which there is no available curative treatment.

[0007] Overexpression of DNM2 in absence of mutation is also involved in some pathophysiological mechanisms of other diseases such X-linked myotubular myopathy or cancers, for example prostate cancer and pancreatic cancer. SUMMARY

[0008] The present disclosure relates to antisense oligomers and related compositions and methods for the treatment of a disease or disorder associated with aberrant DNM2 expression including, but not limited to, a genetic muscle disease or neuromuscular disease. In certain embodiments, the disease or disorder associated with aberrant DNM2 expression is a centronuclear myopathy (CNM).

[0009] In an aspect provided herein, is an antisense oligomer comprising a non-natural chemical backbone and a targeting sequence 13 to 30 bases in length that is complementary to a target region within a pre-mRNA of human dynamin 2 (DNM2) gene represented by SEQ ID NO: 1, wherein the target region is within an exon internal region, an intron internal region, an intron-exon junction, or an exon-intron junction of the human DNM2 gene pre-mRNA.

[0010] In certain embodiments, the target region is within the exon internal region of exon 2 (SEQ ID NO: 2), the intron 1 / exon 2 junction, the exon 2 / intron 2 junction, or the intron internal region of intron 2 (SEQ ID NO: 11) of the human DNM2 gene pre-mRNA.

[0011] In certain embodiments, the target region is within the exon internal region of exon 9 (SEQ ID NO: 6), the intron 8 / exon 9 junction, or the exon 9 / intron 9 junction of the human DNM2 gene pre-mRNA.

[0012] In certain embodiments, the target region is within the exon internal region of exon 12 (SEQ ID NO: 7), the intron 11 / exon 12 junction, or the exon 12 / intron 12 junction of the human DNM2 gene pre-mRNA.

[0013] In certain embodiments, the target region is within the exon internal region of exon 13 (SEQ ID NO: 8), the intron 12 / exon 13 junction, the exon 13 / intron 13 junction, or the intron internal region of intron 12 (SEQ ID NO: 12).

[0014] In certain embodiments, the target region is within the exon internal region of exon 6 (SEQ ID NO: 3), the intron 5 / exon 6 junction, the exon 6 / intron 6 junction, or the intron internal region of intron 6 (SEQ ID NO: 11).

[0015] In certain embodiments, the target region is within the exon internal region of exon 7 (SEQ ID NO: 4), the intron 6 / exon 7 junction, or the exon 7 / intron 7 junction.

[0016] In certain embodiments, the target region is within the exon internal region of exon 8 (SEQ ID NO: 5), the intron 7 / exon 8 junction, or the exon 8 / intron 8 junction.

[0017] In certain embodiments, the target region is within the exon internal region of exon 16 (SEQ ID NO: 9), the intron 15 / exon 16 junction, or the exon 16 / intron 16 junction.

[0018] In certain embodiments, the target region is within the exon internal region of exon 19 (SEQ ID NO: 9), the intron 18 / exon 19 junction, or the exon 18 / intron 18 junction.

[0019] In an aspect provided herein, is an antisense oligomer, or a pharmaceutically acceptable salt thereof, comprising: a non-natural chemical backbone selected from a peptide nucleic acid, a locked nucleic acid, a phosphorodiamidate morpholino oligomer, a 2′-OMe phosphorothioate oligomer, or a combination thereof; and a targeting sequence 13 to 30 bases in length that is complementary to a target region within a pre-mRNA of human dynamin 2 (DNM2) gene represented by SEQ ID NO: 1, wherein the target region is within an exon internal region, an intron internal region, an intron-exon junction, or an exon-intron junction of the human DNM2 gene pre-mRNA.

[0020] In another aspect provided herein, is an antisense oligomer, or a pharmaceutically acceptable salt thereof, having a structure of Formula (I):(I), wherein: A′ is selected from -OH,wherein: R5is -C(O)(O-alkyl)x-OH, wherein x is 3-10 and each alkyl group is, independently at each occurrence, C2-6-alkyl, or R5is selected from H, -C(O)C1-6-alkyl, trityl, monomethoxytrityl, -(C1-6-alkyl)-R6, -(C1-6- heteroalkyl)-R6, -C6-10-aryl-R6, 5-10 membered heteroaryl-R6, -C(O)O-(C1-6-alkyl)-R6, - C(O)O-aryl-R6, -C(O)O-(5-10 membered heteroaryl)-R6, and; R6is selected from -OH, -SH, and -NH2, or R6is O, S, or NH, each of which is covalently linked to a solid support; R9is C1-6alkyl; each R1is independently selected from -OH and -N(R3)(R4), wherein each R3and R4is, independently at each occurrence, -H or -C1-6-alkyl; each R2is independently selected from a naturally or non-naturally occurring nucleobase, which, when taken together, forms a targeting sequence 13 to 30 bases in length that is complementary to a target region within a pre-mRNA of human dynamin 2 (DNM2) gene represented by SEQ ID NO: 1, wherein the target region is within an exon internal region, an intron internal region, an intron-exon junction, or an exon-intron junction of the human DNM2 gene pre-mRNA; t is 11-28; E′ is selected from -H, -C1-6-alkyl, -C(O)C1-6-alkyl, benzoyl, stearoyl, trityl, monomethoxytrityl, dimethoxytrityl, trimethoxytrityl,; wherein: Q is -C(O)(CH2)6C(O)- or -C(O)(CH2)2S2(CH2)2C(O)-; R7is -(CH2)2OC(O)N(R8)2, wherein R8is -(CH2)6NHC(=NH)NH2; L is a linking amino acid, wherein L is covalently-linked by an amide bond to the C-terminus of J; J is a cell-penetrating peptide; and G is selected from -H, -C(O)C1-6-alkyl, benzoyl, and stearoyl, wherein G is covalently-linked to J.

[0021] In an aspect provided herein, is an antisense oligomer, or a pharmaceutically acceptable salt thereof, of Formula (IA):(IA),wherein A′, R2, and t are as described herein. In some embodiments, A′ is a moiety selected from:

[0022] In another aspect provided herein, is antisense oligomer, or a pharmaceutically acceptable salt thereof, of Formula (II):(II), wherein G, R2, and t are as described herein.

[0023] In an aspect provided herein, is an antisense oligomer, or a pharmaceutically acceptable salt thereof, of Formula (III):wherein R2is as described herein, and n is 11-28.

[0024] In an aspect provided herein, is antisense oligomer of Formula (IV):(IV), wherein R2and n are as described herein.

[0025] In an aspect provided herein, is a pharmaceutical composition comprising: an antisense oligomer, or a pharmaceutically acceptable salt thereof, of Formulae (I), (IA), (II), (III), (IV) and / or (V); and a pharmaceutically acceptable carrier.

[0026] In an aspect provided herein, is a method of treating a disease or disorder, or sequelae thereof, associated with aberrant expression of dynamin 2 (DNM2) protein, comprising administering to a subject in need thereof a therapeutically effective amount of an antisense oligomer, or a pharmaceutically acceptable salt thereof, of Formula (I):(I), wherein A′, R1, R2, t, E′, and G are as described herein.

[0027] In another aspect provided herein, is a method of treating a disease or disorder, or sequelae thereof, associated with aberrant expression of dynamin 2 (DNM2) protein, comprising administering to a subject in need thereof a therapeutically effective amount of an antisense oligomer, or a pharmaceutically acceptable salt thereof, of Formula (IA):(IA), wherein A′, R2, and t are as described herein.

[0028] In an aspect provided herein, is a method of treating a disease or disorder, or sequelae thereof, associated with aberrant expression of dynamin 2 (DNM2) protein, comprising administering to a subject in need thereof a therapeutically effective amount of an antisense oligomer, or a pharmaceutically acceptable salt thereof, of Formula (II):wherein G, R2, and t are as described herein.

[0029] In an aspect provided herein, is a method of treating a disease or disorder, or sequelae thereof, associated with aberrant expression of dynamin 2 (DNM2) protein, comprising administering to a subject in need thereof a therapeutically effective amount of an antisense oligomer, or a pharmaceutically acceptable salt thereof, of Formula (III):wherein R2is as described herein, and n is 11-28.

[0030] In another aspect provided herein, is a method of treating a disease or disorder, or sequelae thereof, associated with aberrant expression of dynamin 2 (DNM2) protein, comprising administering to a subject in need thereof a therapeutically effective amount of an antisense oligomer, or a pharmaceutically acceptable salt thereof, of In an aspect provided herein, is antisense oligomer of Formula (IV):(IV), wherein R2and n are as described herein.

[0031] In certain embodiments, the disease or disorder is a genetic muscle disorder. In certain embodiments, the disease or disorder is a neuromuscular disorder. In certain embodiments, the disease or disorder is a centronuclear myopathy (CNM). In certain embodiments, the disease or disorder is myotubular myopathy (XLMTM or XLCNM), autosomal dominant congenital myopathy (ADCNM), autosomal recessive centronuclear myopathy (ARCNM), or Charcot-Marie- Tooth disease (CMT). In certain embodiments, the CMT is DNM2-implicated CMT.

[0032] In certain embodiments, the Charcot-Marie-Tooth disease (CMT) is Charcot-Marie-Tooth disease, dominant intermediate B (CMTDIB or DI-CMTB). In certain embodiments, the Charcot-Marie-Tooth disease is Charcot-Marie-Tooth disease, axonal type 2M (CMT2M). In certain embodiments, the disease or disorder is a hereditary spastic paraplegia (HSP).

[0033] The antisense oligomers disclosed herein are useful in methods of inducing exon skipping to create premature stop codon in a human DNM2 pre-mRNA, thereby triggering nonsense-mediated decay and reducing DNM2-aggregation in diseased cells. Accordingly, the antisense oligomers described herein are useful for the treatment for various diseases in a subject in need thereof, including, but not limited to, diseases such as a centronuclear myopathy. BRIEF DESCRIPTION OF THE FIGURES

[0034] FIGs.1A-1E show normalized DNM2 transcript levels as measured by RT-qPCR after treatment with indicated PMO compounds for exons 6, 8 and 16.1A-1B: RT-qPCR after treatment with indicated PMO compounds for exon 8.1C: RT-qPCR after treatment with indicated PMO compounds for exon 16.1D-1E: RT-qPCR after treatment with indicated PMO compounds for exon 6.

[0035] FIGs.2A-2F show normalized DNM2 transcript levels as measured by RT-qPCR after treatment with indicated PMO compounds for exons 2, 7, 9, 12, 13, and 19.2A: RT-qPCR after treatment with indicated PMO compounds for exon 2.2B: RT-qPCR after treatment with indicated PMO compounds for exon 9.2C: RT-qPCR after treatment with indicated PMO compounds for exon 12.2D: RT-qPCR after treatment with indicated PMO compounds for exon 13.2E: RT-qPCR after treatment with indicated PMO compounds for exon 19.2F: RT-qPCR after treatment with indicated PMO compounds for exon 7.

[0036] FIGs.3A-3J show normalized DNM2 transcript levels as measured by RT-qPCR after treatment with indicated PMO compounds for exons, 2, 9, 12, and 13.3A-3B: transcript levels as measured by RT-qPCR after treatment with indicated PMO compounds for exon 2.3C-3E: transcript levels as measured by RT-qPCR after treatment with indicated PMO compounds for exon 9.3F-3G: transcript levels as measured by RT-qPCR after treatment with indicated PMO compounds for exon 12.3H-3J: transcript levels as measured by RT-qPCR after treatment with indicated PMO compounds for exon 13.

[0037] FIGs.4A-4G show the dose response of PMOs targeted against exons 2, 9, 12, and 13 as measured by RT-qPCR.4A-4B and G: transcript levels as measured by RT-qPCR after treatment with indicated PMO compounds for exon 2.4C-4D: transcript levels as measured by RT-qPCR after treatment with indicated PMO compounds for exon 9.4E: transcript levels as measured by RT-qPCR after treatment with indicated PMO compounds for exon 12.4F: transcript levels as measured by RT-qPCR after treatment with indicated PMO compounds for exon 13.

[0038] FIGs.5A-5B show DNM2 exon skipping confirmation after treatment with select compounds targeting exon 2 and exon 9 as measured by RT-PCR.5A: photographic depiction of DNA agarose gel electrophoresis of DNM2 exon skipping confirmation after treatment with select compounds targeting exon 2.5B: photographic depiction of DNA agarose gel electrophoresis of DNM2 exon skipping confirmation after treatment with select compounds targeting exon 9.

[0039] FIGs.6A-6B show treatment with select exon 2 targeting compound results in DNM2 protein reduction.6A: photographic depiction of capillary electrophoresis of DNM2 protein reduction in RD Cells after treatment with PPMOs.6B: is a graphic representation of exon 2 targeting compound results in DNM2 protein reduction.

[0040] FIG.7 shows normalized DNM2 transcript levels as measured by RT-qPCR after PPMO treatment in AB1190C16PV myoblast immortalized cell line, differentiation method 1.

[0041] FIG.8 shows normalized DNM2 transcript levels as measured by RT-qPCR after PPMO treatment in AB1190C16PV myoblast immortalized cell line, differentiation method 2.

[0042] FIG.9 shows normalized DNM2 transcript levels as measured by RT-qPCR after PPMO treatment in healthy human iPSC derived skeletal muscle.

[0043] FIG.10 shows normalized DNM2 transcript levels as measured by RT-qPCR after PPMO treatment in MTM1 patient derived iPSC myotubes, GM06813 C1.

[0044] FIG.11 shows normalized DNM2 transcript levels as measured by RT-qPCR after PPMO treatment in MTM1 patient derived iPSC myotubes, GM24509 C4.

[0045] FIGs.12A-12G show dose response of normalized DNM2 transcript levels as measured by RT-qPCR with select compounds in GM06813 C1 myotubes.12A: dose response of normalized DNM2 transcript levels as measured by RT-qPCR with PPMO 2 in GM06813 C1 myotubes.12B: dose response of normalized DNM2 transcript levels as measured by RT-qPCR with PPMO 3 in GM06813 C1 myotubes.12C: dose response of normalized DNM2 transcript levels as measured by RT-qPCR with PPMO 4 in GM06813 C1 myotubes.12D: dose response of normalized DNM2 transcript levels as measured by RT-qPCR with PPMO 5 in GM06813 C1 myotubes.12E: dose response of normalized DNM2 transcript levels as measured by RT-qPCR with PPMO 6 in GM06813 C1 myotubes.12F: dose response of normalized DNM2 transcript levels as measured by RT-qPCR with PPMO 7 in GM06813 C1 myotubes.12G: dose response of normalized DNM2 transcript levels as measured by RT-qPCR with PPMO 8 in GM06813 C1 myotubes.

[0046] FIGs.13A-13D show DNM2 exon skipping confirmation in myotubes after treatment with indicated PPMO compounds as measured by RT-PCR.13A: DNM2 exon skipping confirmation in myotubes after treatment with PPMO 10 as measured by RT-PCR.13B: DNM2 exon skippingconfirmation in myotubes after treatment with PPMOs 14, 22, and 28 as measured by RT-PCR. 13C: DNM2 exon skipping confirmation in myotubes after treatment with PPMO 12 as measured by RT-PCR.13D: DNM2 exon skipping confirmation in myotubes after treatment with PPMOs 27 and 28 as measured by RT-PCR.

[0047] FIGs.14A-14D show DNM2 exon skipping confirmation in myotubes after treatment with indicated PPMO compounds as measured by RT-PCR.14A: DNM2 exon skipping confirmation in myotubes after treatment with PPMO 29 as measured by RT-PCR.14B: DNM2 exon skipping confirmation in myotubes after treatment with PPMOs 30, 22, and 28 as measured by RT-PCR. 14C: DNM2 exon skipping confirmation in myotubes after treatment with PPMOs 1 and 29 as measured by RT-PCR.14D: DNM2 exon skipping confirmation in myotubes after treatment with PPMO 35 as measured by RT-PCR.

[0048] FIGs.15A-15B show DNM2 protein reduction in myotubes after treatment with indicated PPMO compounds.15A: photographic depiction of a Western blot of DNM2 protein reduction in myotubes after treatment with PPMOs 10, 27, and 28.15B: a graphic representation of DNM2 protein reduction in myotubes after treatment with PPMOs 10, 27, and 28.

[0049] FIGs.16A-16B show DNM2 protein reduction in myotubes after treatment with indicated PPMO compounds.16A: photographic depiction of a Western blot of DNM2 protein reduction in myotubes after treatment with PPMOs 1, 29, and 35.16B: a graphic representation of DNM2 protein reduction in myotubes after treatment with PPMOs 1, 29, and 35. DETAILED DESCRIPTION

[0050] Provided herein is an antisense oligomer or pharmaceutically acceptable salt thereof, comprising a modified chemical backbone and a targeting sequence of 13 to 30 bases in length that is complementary to a target region within a pre-mRNA of the human DNM2 gene (SEQ ID NO: 1). The target region may be an intron / exon junction or an exon internal region of the human DNM2 gene pre-mRNA. Such antisense oligomers are useful for the treatment of various diseases in a subject in need thereof, including, but not limited to, centronuclear myopathies (CNM).

[0051] Certain embodiments relate to methods of inducing exon skipping to create a premature stop codon on a human DNM2 pre-mRNA in a cell, comprising contacting the cell with an antisense oligomer of sufficient length and complementarity to specifically hybridize to a region within the human DNM2 gene, such that the expression of DNM2 is reduced. In some embodiments, the cell is in a subject, and the method comprises administering the antisense oligomer to the subject. In some embodiments, the cell is a diseased cell.

[0052] In some embodiments, the antisense oligomer further comprises a cell-penetrating peptide, an antibody, an antibody fragment, or an antigen fragment of an antibody. In particular,the antisense oligomer comprises a cell penetrating peptide, wherein the cell-penetrating peptide is any of the peptides provided herein or known in the art.

[0053] Also provided herein are pharmaceutical compositions and methods for treating diseases or disorders, or sequelae thereof, associated with aberrant expression of dynamin 2 (DNM2) protein. I. Definitions

[0054] Unless otherwise indicated, the following terms used herein have the following meanings:

[0055] The term “about” will be understood by persons of ordinary skill in the art and will vary to some extent on the context in which it is used. As used herein when referring to a measurable value such as an amount, a temporal duration, and the like, the term “about” is meant to encompass variations of ±10%, including ±5%, ±1%, and ±0.1% from the specified value, as such variations are appropriate to perform the disclosed methods.

[0056] The term “alkyl” refers to saturated, straight- or branched-chain hydrocarbon moieties containing, in certain embodiments, between one and six, or one and eight carbon atoms, respectively. Examples of C1-6-alkyl moieties include, but are not limited to, methyl, ethyl, propyl, isopropyl, n-butyl, tert-butyl, neopentyl, n-hexyl moieties; and examples of C1-8-alkyl moieties include, but are not limited to, methyl, ethyl, propyl, isopropyl, n-butyl, tert-butyl, neopentyl, n- hexyl, heptyl, and octyl moieties.

[0057] The number of carbon atoms in an alkyl substituent can be indicated by the prefix “Cx-y,” or “Cx-Cy” where x is the minimum and y is the maximum number of carbon atoms in the substituent. Likewise, a Cxchain means an alkyl chain containing x carbon atoms.

[0058] The term “heteroalkyl” by itself or in combination with another term means, unless otherwise stated, a stable straight or branched chain alkyl group consisting of the stated number of carbon atoms and up to five heteroatoms selected from O, N, S, and P, wherein the nitrogen, sulfur, and phosphorus atoms may be optionally oxidized, and the nitrogen heteroatom may be optionally quaternized. The heteroatom(s) may be placed at any position of the heteroalkyl group, including between the rest of the heteroalkyl group and the fragment to which it is attached, as well as attached to the most distal carbon atom in the heteroalkyl group. Examples include: -O-CH2-CH2-, -O-CH2-CH2-CH3, -CH2-CH2-CH2-OH, -(O-CH2-CH2)3-OH-, -CH2-CH2-NH- CH3, -CH2-S-CH2-CH3, and -CH2-CH2-S(=O)-CH3. Up to three heteroatoms may be consecutive, such as, for example, -CH2-NH-OCH3, or -CH2-CH2-S-S-CH3.

[0059] The term “aryl,” employed alone or in combination with other terms, means, unless otherwise stated, a carbocyclic aromatic system containing one or more rings (typically one, two, or three rings), wherein such rings may be attached together in a pendent manner, such as abiphenyl, or may be fused, such as naphthalene. Examples of aryl groups include phenyl, anthracyl, and naphthyl. In various embodiments, examples of an aryl group may include phenyl (i.e., C6-aryl) and biphenyl (i.e., C12-aryl). In some embodiments, aryl groups have from six to sixteen carbon atoms (i.e., C6-16-aryl). In some embodiments, aryl groups have from six to twelve carbon atoms (i.e., C6-12-aryl). In some embodiments, aryl groups have six carbon atoms (i.e., C6-aryl).

[0060] As used herein, the term “heteroaryl” or “heteroaromatic” refers to a heterocycle having aromatic character. Heteroaryl substituents may be described by the number of carbon atoms, e.g., C1-9-heteroaryl indicates the number of carbon atoms contained in the heteroaryl group without including the number of heteroatoms. For example, a C1-9-heteroaryl will include an additional one to four heteroatoms. A polycyclic heteroaryl may include one or more rings that are partially saturated. Non-limiting examples of heteroaryls include pyridyl, pyrazinyl, pyrimidinyl (including, e.g., 2- and 4-pyrimidinyl), pyridazinyl, thienyl, furyl, pyrrolyl (including, e.g., 2-pyrrolyl), imidazolyl, thiazolyl, oxazolyl, pyrazolyl (including, e.g., 3- and 5-pyrazolyl), isothiazolyl, 1,2,3-triazolyl, 1,2,4-triazolyl, 1,3,4-triazolyl, tetrazolyl, 1,2,3-thiadiazolyl, 1,2,3-oxadiazolyl, 1,3,4-thiadiazolyl and 1,3,4-oxadiazolyl.

[0061] Non-limiting examples of polycyclic heterocycles and heteroaryls include indolyl (including, e.g., 3-, 4-, 5-, 6- and 7-indolyl), indolinyl, quinolyl, tetrahydroquinolyl, isoquinolyl (including, e.g., 1- and 5-isoquinolyl), 1,2,3,4-tetrahydroisoquinolyl, cinnolinyl, quinoxalinyl (including, e.g., 2- and 5-quinoxalinyl), quinazolinyl, phthalazinyl, 1,8-naphthyridinyl, 1,4-benzodioxanyl, coumarin, dihydrocoumarin, 1,5-naphthyridinyl, benzofuryl (including, e.g., 3-, 4-, 5-, 6- and 7-benzofuryl), 2,3-dihydrobenzofuryl, 1,2-benzisoxazolyl, benzothienyl (including, e.g., 3-, 4-, 5-, 6-, and 7-benzothienyl), benzoxazolyl, benzothiazolyl (including, e.g., 2-benzothiazolyl and 5-benzothiazolyl), purinyl, benzimidazolyl (including, e.g., 2-benzimidazolyl), benzotriazolyl, thioxanthinyl, carbazolyl, carbolinyl, acridinyl, pyrrolizidinyl, and quinolizidinyl.

[0062] The term “protecting group” or “chemical protecting group” refers to chemical moieties that block some or all reactive moieties of a compound and prevent such moieties from participating in chemical reactions until the protective group is removed, for example, those moieties listed and described in T.W. Greene, P.G.M. Wuts, Protective Groups in Organic Synthesis, 3rd ed. John Wiley & Sons (1999). It may be advantageous, where different protecting groups are employed, that each (different) protective group be removable by a different means. Protective groups that are cleaved under totally disparate reaction conditions allow differential removal of such protecting groups. For example, protective groups can be removed by acid, base, and hydrogenolysis. Groups such as trityl, monomethoxytrityl,dimethoxytrityl, acetal and tert-butyldimethylsilyl are acid labile and may be used to protect carboxy and hydroxy reactive moieties in the presence of amino groups protected with Cbz groups, which are removable by hydrogenolysis, and Fmoc groups, which are base labile. Carboxylic acid moieties may be blocked with base labile groups such as, without limitation, methyl, or ethyl, and hydroxy reactive moieties may be blocked with base labile groups such as acetyl in the presence of amines blocked with acid labile groups such as tert-butyl carbamate or with carbamates that are both acid and base stable but hydrolytically removable.

[0063] Carboxylic acid and hydroxyl reactive moieties may also be blocked with hydrolytically removable protective groups such as the benzyl group, while amine groups may be blocked with base labile groups such as Fmoc. A particularly useful amine protecting group for the synthesis of compound of Formula (I) is trifluoroacetamide. Carboxylic acid reactive moieties may be blocked with oxidatively-removable protective groups such as 2,4-dimethoxybenzyl, while coexisting amino groups may be blocked with fluoride labile silyl carbamates.

[0064] Allyl blocking groups are useful in the presence of acid- and base-protecting groups since the former are stable and can be subsequently removed by metal or pi-acid catalysts. For example, an allyl-blocked carboxylic acid can be deprotected with a palladium(0)-catalyzed reaction in the presence of acid labile t-butyl carbamate or base-labile acetate amine protecting groups. Yet another form of protecting group is a resin to which a compound or intermediate may be attached. Provided that the residue is attached to the resin, that functional group is blocked and cannot react. Once released from the resin, the functional group is available to react.

[0065] The term “nucleobase,” “base pairing moiety,” “nucleobase-pairing moiety,” or “base” refers to the heterocyclic ring portion of a nucleoside, nucleotide, and / or morpholino subunit. Nucleobases may be naturally occurring (e.g., uracil, thymine, adenine, cytosine, and guanine), or may be modified or analogs of these naturally occurring nucleobases, e.g., one or more nitrogen atoms of the nucleobase may be independently at each occurrence replaced by carbon. Exemplary analogs include hypoxanthine (the base component of the nucleoside inosine); 2, 6-diaminopurine; 5-methyl cytosine; C5-propynyl-modified pyrimidines; 10-(9- (aminoethoxy)phenoxazinyl) (G-clamp) and the like.

[0066] Further examples of base pairing moieties include, but are not limited to, uracil, thymine, adenine, cytosine, guanine and hypoxanthine having their respective amino groups protected by acyl protecting groups, 2-fluorouracil, 2-fluorocytosine, 5-bromouracil, 5-iodouracil, 2,6- diaminopurine, azacytosine, pyrimidine analogs such as pseudoisocytosine and pseudouracil and other modified nucleobases such as 8-substituted purines, xanthine, or hypoxanthine (the latter two being the natural degradation products). The modified nucleobases disclosed in Chiuand Rana (2003) RNA 9:1034-1048, Limbach et al. (1994) Nucleic Acids Res.22:2183-2196 and Revankar and Rao, Comprehensive Natural Products Chemistry, vol.7, 313, are also contemplated, the contents of which are incorporated herein by reference.

[0067] Further examples of base pairing moieties include, but are not limited to, expanded-size nucleobases in which one or more benzene rings have been added. Nucleic base replacements described in the Glen Research catalog (www.glenresearch.com); Krueger AT et al. (2007) Acc. Chem. Res.40:141-150; Kool ET (2002) Acc. Chem. Res.35:936-943; Benner SA et al. (2005) Nat. Rev. Genet.6:553-543; Romesberg FE et al. (2003) Curr. Opin. Chem. Biol.7:723-733; Hirao, I (2006) Curr. Opin. Chem. Biol.10:622-627, the contents of which are incorporated herein by reference, are contemplated as useful for the synthesis of the oligomers described herein. Examples of expanded-size nucleobases are shown below:

[0068] As used herein, the terms “-G-R6” and “-G-R6-Ac” and “R6G” are used interchangeably and refer to a peptide moiety conjugated to an antisense oligomer of the disclosure. In various embodiments, “G” represents a glycine residue conjugated to “R6” by an amide bond, and each “R” represents an arginine residue conjugated together by amide bonds such that “R6” means six (6) arginine residues conjugated together by amide bonds. The arginine residues can have any stereo configuration, for example, the arginine residues can be L-arginine residues, D-arginine residues, or a mixture of D- and L-arginine residues. In certain embodiments, “-G-R6” or “-G-R6-Ac” is conjugated to the morpholine ring nitrogen of the 3′ most morpholino subunit of a PMO antisense oligomer of the disclosure. In some embodiments, “-G-R6” or “-G-R6-Ac” is conjugated to the 3′ end of an antisense oligomer of the disclosure and is of the following formula:.

[0069] The terms “oligonucleotide” or “oligomer” refer to a compound comprising a plurality of linked nucleosides, nucleotides, or a combination of both nucleosides and nucleotides. In specific embodiments provided herein, an oligonucleotide is a morpholino oligonucleotide.

[0070] The term “nucleoside” means a compound comprising a nucleobase and a sugar moiety. The nucleobase and sugar moiety are each, independently, unmodified or modified. “Modified nucleoside” means a nucleoside comprising a modified nucleobase and / or a modified sugar moiety. Modified nucleosides include abasic nucleosides, which lack a nucleobase. In certain embodiments, the antisense oligonucleotides comprising an abasic subunit have the partial structure:

[0071] In certain embodiments, modified oligonucleotides comprise one or more nucleosides comprising a modified nucleobase. In certain embodiments, modified oligonucleotides comprise one or more nucleosides that do not comprise a nucleobase, referred to as an abasic nucleoside. With reference to an oligonucleotide, “subunit” refers to a nucleotide, nucleoside, nucleobase, or sugar, or a modified nucleotide, nucleoside, nucleobase, or sugar as provided herein.

[0072] As used herein, the terms “antisense oligomer” or “antisense compound” are used interchangeably and refer to a sequence of subunits, each having a base carried on a backbone subunit composed of ribose or other pentose sugar or morpholino group, and where the backbone groups are linked by intersubunit linkages that allow the bases in the compound to hybridize to a target sequence in a nucleic acid (typically an RNA) by Watson-Crick base pairing, to form a nucleic acid:oligomer heteroduplex within the target sequence. The oligomer may have exact sequence complementarity to the target sequence or nearly exact complementarity. Such antisense oligomers are designed to block or inhibit translation of the mRNA containing the target sequence and may be said to be “directed to” a sequence with which it hybridizes.

[0073] Also contemplated herein as types of “antisense oligomers” or “antisense compounds” are phosphorothioate-modified oligomers, peptide nucleic acids (PNAs), locked nucleic acids (LNAs), 2′-fluoro-modified oligomers, 2′-O,4′-C-ethylene-bridged nucleic acids (ENAs), tricyclo- DNAs, tricylo-DNA phosphorothioate-modified oligomers, 2′-O-[2-(N-methylcarbamoyl) ethyl] modified oligomers, 2′-O-methyl phosphorothioate modified oligomers, 2′-O-methoxyethyl (2′-O- MOE) modified oligomers, and 2′-O-Methyl oligonucleotides, or combinations thereof, as well as other antisense agents known in the art.

[0074] An antisense oligomer “specifically hybridizes” to a target polynucleotide if the oligomer hybridizes to the target under physiological conditions, with a Tm greater than 37 °C, greater than 45 °C, at least 50 °C, and typically 60 °C-80 °C or higher. The “Tm” of an oligomer is the temperature at which 50% hybridizes to a complementary polynucleotide. Tm is determined under standard conditions in physiological saline, as described, for example, in Miyada et al. (1987) Methods Enzymol.154:94-107. Such hybridization may occur with “near” or “substantial” complementarity of the antisense oligomer to the target sequence, as well as with exact complementarity.

[0075] The terms “complementary” and “complementarity” refer to oligonucleotides (i.e., a sequence of nucleotides) related by base-pairing rules. For example, the sequence “T-G-A (5′- 3′)” is complementary to the sequence “T-C-A (5′-3′).” Complementarity may be “partial,” in which only some of the nucleic acids’ bases are matched according to base pairing rules, or there may be “complete,” “total,” or “perfect” (100%) complementarity between the nucleic acids. The degree of complementarity between nucleic acid strands has significant effects on the efficiency and strength of hybridization between nucleic acid strands. In some embodiments, oligonucleotides can include one or more mismatches (e.g., 6, 5, 4, 3, 2, or 1 mismatches) with respect to the target RNA. Such hybridization may occur with “near” or “substantial” complementarity of the antisense oligomer to the target sequence, as well as with exact complementarity. In some embodiments, an oligomer may hybridize to a target sequence with about 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 99% or 100% complementarity. Variations at any location within the oligomer are included. In certain embodiments, variations in sequence near the termini of an oligomer, if present, are typically within about 6, 5, 4, 3, 2, or 1 nucleotides of the 5′-terminus, 3′-terminus, or both termini.

[0076] The terms “TEG,” “EG3,” or “triethylene glycol tail” refer to triethylene glycol moieties conjugated to the oligomer, e.g., at its 3′- or 5′-end. For example, in some embodiments, “TEG” includes, for example, wherein A′ of the conjugate of Formula (I) is of the formula:.

[0077] Naturally occurring nucleotide bases include adenine, guanine, cytosine, thymine, and uracil, which have the symbols A, G, C, T, and U, respectively. Nucleotide bases can also encompass analogs of naturally occurring nucleotide bases. Base pairing typically occurs between purine A and pyrimidine T or U, and between purine G and pyrimidine C.

[0078] Oligonucleotides may also include nucleobase modifications or substitutions. Oligonucleotides containing a modified or substituted base include oligonucleotides in which one or more purine or pyrimidine bases most found in nucleic acids are replaced with less common or non-natural bases. In some embodiments, the nucleobase is covalently linked at the N9 atom of the purine base, or at the N1 atom of the pyrimidine base, to the morpholine ring of a nucleotide or nucleoside.

[0079] Purine bases comprise a pyrimidine ring fused to an imidazole ring, as described by the general formula:.

[0080] Adenine and guanine are the two purine nucleobases most found in nucleic acids. These may be substituted with other naturally occurring purines, including, but not limited to, N6- methyladenine, N2-methylguanine, hypoxanthine, and 7-methylguanine.

[0081] Pyrimidine bases comprise a six-membered pyrimidine ring as described by the general formula:.

[0082] Cytosine, uracil, and thymine are the pyrimidine bases most found in nucleic acids. These may be substituted with other naturally occurring pyrimidines, including, but not limited to, 5-methylcytosine, 5-hydroxymethylcytosine, pseudouracil, and 4-thiouracil. In one embodiment, the oligonucleotides described herein contain thymine bases in place of uracil.

[0083] Other modified or substituted bases include, but are not limited to, 2,6-diaminopurine, orotic acid, agmatidine, lysidine, 2-thiopyrimidine (e.g.2-thiouracil, 2-thiothymine), G-clamp and its derivatives, 5-substituted pyrimidine (e.g.5-halouracil, 5-propynyluracil, 5-propynylcytosine, 5-aminomethyluracil, 5-hydroxymethyluracil, 5-aminomethylcytosine, 5-hydroxymethylcytosine, Super T), 7-deazaguanine, 7-deazaadenine, 7-aza-2,6-diaminopurine, 8-aza-7-deazaguanine, 8-aza-7-deazaadenine, 8-aza-7-deaza-2,6-diaminopurine, Super G, Super A, and N4- ethylcytosine, or derivatives thereof; N2-cyclopentylguanine (cPent-G), N2-cyclopentyl-2- aminopurine (cPent-AP), and N2-propyl-2-aminopurine (Pr-AP), pseudouracil or derivatives thereof; and degenerate or universal bases, like 2,6-difluorotoluene or absent bases like abasic sites (e.g.1-deoxyribose, 1,2-dideoxyribose, 1-deoxy-2-O-methylribose; or pyrrolidine derivatives in which the ring oxygen has been replaced with nitrogen (azaribose)). Pseudouracilis a naturally occurring isomerized version of uracil, with a C-glycoside rather than the regular N- glycoside as in uridine.

[0084] In some embodiments, modified or substituted nucleobases are useful for facilitating the purification of antisense oligonucleotides. For example, in certain embodiments, antisense oligonucleotides may contain three or more (e.g., 3, 4, 5, 6, or more) consecutive guanine bases. In certain antisense oligonucleotides, a string of three or more consecutive guanine bases can result in aggregation of the oligonucleotides, complicating purification. In such antisense oligonucleotides, one or more of the consecutive guanines can be substituted with hypoxanthine. The substitution of hypoxanthine for one or more guanines in a string of three or more consecutive guanine bases can reduce aggregation of the antisense oligonucleotide, thereby facilitating purification.

[0085] The oligonucleotides provided herein are synthesized and do not include antisense compositions of biological origin. The molecules of the disclosure may also be mixed, encapsulated, conjugated, or otherwise associated with other molecules, molecule structures, or mixtures of compounds, as for example, liposomes, receptor-targeted molecules, oral, rectal, topical, or other formulations, for assisting in uptake, distribution, or absorption, or a combination thereof.

[0086] As used herein, a “nucleic acid analog” refers to a non-naturally occurring nucleic acid molecule. A nucleic acid is a polymer of nucleotide subunits linked together into a linear structure. Each nucleotide consists of a nitrogen-containing aromatic base attached to a pentose (five-carbon) sugar, which is in turn attached to a phosphate group. Successive phosphate groups are linked together through phosphodiester bonds to form the polymer. The two common forms of naturally occurring nucleic acids are deoxyribonucleic acid (DNA) and ribonucleic acid (RNA). One end of the chain carries a free phosphate group attached to the 5′-carbon atom of a sugar moiety; this is called the 5′ end of the molecule. The other end has a free hydroxyl (-OH) group at the 3′-carbon of a sugar moiety and is called the 3′ end of the molecule. A nucleic acid analog can include one or more non-naturally occurring nucleobases, sugars, and / or internucleotide linkages, for example, a phosphorodiamidate morpholino oligomer (PMO). As disclosed herein, in certain embodiments, a “nucleic acid analog” is a PMO, and in certain embodiments, a “nucleic acid analog” is a positively charged cationic PMO.

[0087] A “morpholino oligomer” or “PMO” refers to a polymeric molecule having a backbone that supports bases capable of hydrogen bonding to typical polynucleotides, wherein the polymer lacks a pentose sugar backbone moiety, and more specifically a ribose backbone linked by phosphodiester bonds which is typical of nucleotides and nucleosides, but instead contains a ring nitrogen with coupling through the ring nitrogen. An exemplary “morpholino” oligomer comprisesmorpholino subunit structures linked together by phosphoramidate or phosphorodiamidate linkages, joining the morpholino nitrogen of one subunit to the 5′ exocyclic carbon of an adjacent subunit, each subunit comprising a purine or pyrimidine base-pairing moiety effective to bind, by base-specific hydrogen bonding, to a base in a polynucleotide. Morpholino oligomers (including antisense oligomers) are detailed, for example, in U.S. Pat. Nos.5,034,506; 5,142,047; 5,166,315; 5,185,444; 5,217,866; 5,506,337; 5,521,063; 5,698,685; 8,076,476; and 8,299,206; and PCT publication number WO 2009 / 064471, all of which are incorporated herein by reference in their entirety.

[0088] A preferred morpholino oligomer is a phosphorodiamidate-linked morpholino oligomer, referred to herein as a PMO. Such oligomers are composed of morpholino subunit structures such as those shown below:where X is NH2, NHR, or NR2 (where R is lower alkyl, (e.g., methyl)), Y1 is O, and Z is O, and Pi and Pj are purine or pyrimidine base-pairing moieties effective to bind, by base-specific hydrogen bonding, to a base in a polynucleotide. Also preferred are structures having an alternate phosphorodiamidate linkage, where X is lower alkoxy, such as methoxy or ethoxy, Y1 is NH or NR, where R is lower alkyl, and Z is O.

[0089] Representative PMOs include PMOs wherein the intersubunit linkages are linkage (A1). See Table 1.Table 1. Representative Intersubunit Linkages

[0090] A “phosphoramidate” group comprises phosphorus having three attached oxygen atoms and one attached nitrogen atom, while a “phosphorodiamidate” group comprises phosphorus having two attached oxygen atoms and two attached nitrogen atoms. A representative phosphorodiamidate example is below:where each Piis independently selected from H, a nucleobase, and a nucleobase functionalized with a chemical protecting-group, wherein the nucleobase independently at each occurrence comprises a pyridine, a pyrimidine, a triazinane, purine, or a deaza-purine; and n is an integer of 6-38 (i.e., n is 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, or 38). The ring nitrogen of the subunit at the 3′ terminus of a PMO may be capped with a capping group such as acetyl or may be uncapped with a free hydrogen.

[0091] In the uncharged or the modified intersubunit linkages of the antisense oligomers described herein, one nitrogen is always pendant to the backbone chain. The second nitrogen, in a phosphorodiamidate linkage, is typically the ring nitrogen in a morpholino ring structure.

[0092] PMOs are water-soluble, uncharged, or substantially uncharged antisense molecules that inhibit gene expression by preventing binding or progression of splicing or translational machinery components. PMOs have also been shown to inhibit or block viral replication (Stein, Skilling et al.2001; McCaffrey, Meuse et al.2003), and are highly resistant to enzymatic digestion (Hudziak, Barofsky et al.1996). PMOs have demonstrated high antisense specificity and efficacy in vitro in cell-free and cell culture models (Stein, Foster et al.1997; Summerton and Weller 1997), and in vivo in zebrafish, frog, and sea urchin embryos (Heasman, Kofron et al.2000; Nasevicius and Ekker 2000), as well as in adult animal models, such as rats, mice, rabbits, dogs, and pigs (see e.g. Arora and Iversen 2000; Qin, Taylor et al.2000; Iversen 2001;Kipshidze, Keane et al.2001; Devi 2002; Devi, Oldenkamp et al.2002; Kipshidze, Kim et al. 2002; Ricker, Mata et al.2002).

[0093] Antisense PMO oligomers have been shown to be taken up into cells and to be more consistently effective in vivo, with fewer nonspecific effects, than other widely used antisense oligonucleotides (see e.g., P. Iversen, “Phosphoramidite Morpholino Oligomers,” in Antisense Drug Technology, S.T. Crooke, ed., Marcel Dekker, Inc., New York, 2001). Conjugation of PMOs to arginine-rich peptides has been shown to increase their cellular uptake (see e.g., U.S. Patent No.7,468,418, incorporated herein by reference in its entirety).

[0094] “Charged,” “uncharged,” “cationic,” and “anionic” as used herein refer to the predominant state of a chemical moiety at near-neutral pH, e.g., about 6 to 8. For example, the term may refer to the predominant state of the chemical moiety at physiological pH, that is, at about 7.4.

[0095] A “cationic PMO” or “PMO+” refers to a phosphorodiamidate morpholino oligomer comprising any number of (1-piperazino)phosphinylideneoxy, (1-(4-(^-guanidino-alkanoyl))- piperazino)phosphinylideneoxy linkages (A2 and A3; see Table 1) that have been described previously (see e.g., PCT publication WO 2008 / 036127 which is incorporated herein by reference in its entirety).

[0096] The “backbone” of an antisense oligomer (e.g., an uncharged oligonucleotide analog) refers to the structure supporting the base-pairing moieties, e.g., for a morpholino oligomer, as described herein, the “backbone” includes morpholino ring structures connected by intersubunit linkages (e.g., phosphorus-containing linkages). A “substantially uncharged backbone” refers to the backbone of an oligonucleotide analogue wherein less than 50% of the intersubunit linkages are charged at near-neutral pH. For example, a substantially uncharged backbone may comprise less than 50%, less than 40%, less than 30%, less than 20%, less than 10%, less than 5% or even 0% intersubunit linkages which are charged at near neutral pH. In some embodiments, the substantially uncharged backbone comprises at most one charged (at physiological pH) intersubunit linkage for every four uncharged (at physiological pH) linkages, at most one for every eight or at most one for every sixteen uncharged linkages. In some embodiments, the nucleic acid analogs described herein are fully uncharged.

[0097] In certain embodiments, the compounds described herein comprise or consist of an oligonucleotide comprising a targeting base sequence that is complementary to a target nucleic acid. In certain embodiments, the target nucleic acid is an endogenous RNA molecule. In certain embodiments, the target nucleic acid encodes a protein. In certain embodiments, the target nucleic acid is non-coding. In certain such embodiments, the target nucleic acid is selected from an mRNA and a pre-mRNA, including intronic, exonic and untranslated regions. In certain embodiments, the target RNA is an mRNA. In certain embodiments, the target nucleic acid is apre-mRNA. In certain such embodiments, the target region is entirely within an exon. In certain such embodiments, the target region is entirely within an intron. In certain embodiments, the target region spans an intron / exon junction. In certain embodiments, the target region is at least 50% within an intron.

[0098] The term “targeting base sequence” or “targeting sequence” is the (nucleobase) sequence in the antisense oligomer that is complementary or substantially complementary to a target nucleic acid. The entire sequence, or only a portion, of the oligomer compound may be complementary to the target sequence.

[0099] The “target region” refers to a sequence in a nucleic acid that is targeted by, and is therefore complementary, substantially complementary, or partially complementary, to the targeting sequence of the antisense oligomer. The entire sequence, or only a portion, of the target region may be complementary to the targeting sequence of the oligomer compound described herein. In certain embodiments, a plurality of antisense compounds is directed to a single target region. In certain embodiments, a nomenclature system according to gene, species, exon number, and annealing coordinates is used herein to identify or indicate a target region or annealing coordinates of a targeted nucleic acid (e.g., a nucleic acid transcript) as follows: G SpZA / D (±X±Y), where G is gene name; Sp is species (e.g., “H” for human, “M” for mouse); Z is exon number; A / D is selected from acceptor (A) and donor (D); The symbol “–“ denotes an intronic position; The symbol “+” denotes an exonic position; X is the position of the first 5′ base relative to A or D site; and Y is the position of the first 3′ base relative to A or D site.

[0100] The nomenclature begins with the name of the transcript (e.g., dynamin 2; DNM2), then the species of the target mRNA (e.g., H: human or M: mouse), followed by the target exon number of the specified transcript and specification of an acceptor (A) or donor (D) site. The annealing coordinates are shown in brackets within the pre-mRNA transcript. The intronic bases are designated with a negative prefix (-) and the exonic position with a positive (+) symbol. The annealing coordinates are the positions of bases relative to the bases relative to the acceptor or donor sites of the reference transcript as denoted by National Center for Biotechnology Information and Ensembl genome browser 96. See, for example, international applicationWO2006 / 000057; Aung-Htut, et al. (2019) Int. J. Mol. Sci.20:5030; and Mann, et al. (2002) J Gene Med.4:644.

[0101] As an example, entirely exonic annealing coordinates represented by H5A(+76+100) indicates the site within the 76thand 100thnucleotides as measured from the 5′ end of an exon 5 (e.g., exon 5 of human DNM2 gene pre-mRNA) (i.e., the region within the 76thand 100thnucleotides as measured from the start of exon 5 at the 5′ end). The closest splice site is the acceptor; therefore, these coordinates are preceded with “A.”

[0102] As another example, DNM2 H2D (+13-12) indicates the last 13 exonic bases and the first 12 intronic bases of the target exon donor splice site (i.e., the target region within the 13thnucleotide of exon 2 measured from the 3′ end of exon 2 to the 12thnucleotide of intron 2 measured from the 3′ end of exon 2 (e.g., human exon 2 of the human DNM2 gene pre-mRNA). The closest splice site is the donor; therefore, these coordinates are preceded with “D.”

[0103] As another example, DNM2 H13A(-8+17) indicates the last 8 bases of the intron preceding the target exon 2 and the first 17 bases of the target exon 2 (i.e., the target region within the 8thnucleotide of intron 12 measured from the 5′ end of exon 13 to the 17thnucleotide of exon 13 measured from the 5′ end of exon 13). The closest splice site is the acceptor; therefore, these coordinates are preceded with “A.”

[0104] The term “peptide” refers to a compound comprising a plurality of linked amino acids. In certain embodiments, the peptides provided herein are cell-penetrating peptides (CPP).

[0105] As used herein, a “cell-penetrating peptide” (CPP) or “carrier peptide” is a relatively short peptide capable of promoting the uptake of PMOs by cells, thereby delivering the PMOs to the interior (cytoplasm) of the cells. The CPP or carrier peptide typically is about 12 to about 40 amino acids long. The length of the carrier peptide is not particularly limited and varies in different embodiments. In some embodiments, the carrier peptide comprises from 4 to 40 amino acid subunits. In other embodiments, the carrier peptide comprises from 6 to 30, from 6 to 20, from 8 to 25, or from 10 to 20 amino acid subunits. In various embodiments, the CPPs disclosed herein comprise an arginine-rich peptide as described further below.

[0106] As used herein, a “peptide-conjugated phosphorodiamidate-linked morpholino oligomer” or “PPMO” refers to a PMO covalently linked to a peptide, such as a cell-penetrating peptide (CPP) or carrier peptide. The cell-penetrating peptide promotes the uptake of the PMO by cells, thereby delivering the PMO to the interior (cytoplasm) of the cells. Depending on its amino acid sequence, a CPP can be generally effective, or it can be specifically or selectively effective for PMO delivery to a particular type or particular types of cells. PMOs and CPPs are typically linked at their ends, e.g., the C-terminal end of the CPP can be linked to the 5′ end of the PMO, or the 3′ end of the PMO can be linked to the N-terminal end of the CPP. PPMOs can includeuncharged PMOs, charged (e.g., cationic) PMOs, and mixtures thereof. In an embodiment, the linking moiety of the conjugates described herein may be cleaved to release a PPMO.

[0107] The carrier peptide may be linked to the nucleic acid analog either directly or via an optional linker, e.g., one or more additional naturally occurring amino acids, e.g., cysteine (C), glycine (G), or proline (P), or additional amino acid analogs, e.g., 6-aminohexanoic acid (X), beta-alanine (B), or XB. Other linking moieties known in the art may also be employed.

[0108] An “amino acid subunit” is generally an ^-amino acid residue (–CO-CHR-NH-); but may also be a ^- or other amino acid residue (e.g., -CO-CH2CHR-NH-), where R is an amino acid side chain.

[0109] The term “naturally occurring amino acid” refers to an amino acid present in proteins found in nature; examples include Alanine (A), Cysteine (C), Aspartic acid (D), Glutamic acid (E), Phenyalanine (F), Glycine (G), Histidine (H), Isoleucine (I), Lysine (K), Leucine (L). Methionine (M), Asparagine (N), Proline (P), Glutamine (Q), Arginine (R), Serine (S), Threonine (T), Valine (V), Tryptophan (W), and Tyrosine (Y). The term “non-natural amino acids” refers to those amino acids not present in proteins found in nature; examples include beta-alanine (β-Ala) and 6-aminohexanoic acid (Ahx).

[0110] An agent is “actively taken up by mammalian cells” when the agent can enter the cell by a mechanism other than passive diffusion across the cell membrane. The agent may be transported, for example, by “active transport,” referring to transport of agents across a mammalian cell membrane by, e.g., an ATP-dependent transport mechanism, or by “facilitated transport,” referring to transport of antisense agents across the cell membrane by a transport mechanism that requires binding of the agent to a transport protein, which then facilitates passage of the bound agent across the membrane.

[0111] As used herein, an “effective amount” refers to any amount of a substance that is sufficient to achieve a desired biological result. A “therapeutically effective amount” refers to any amount of a substance that is sufficient to achieve a desired therapeutic result.

[0112] As used herein, a “subject” is a mammal, which can include a mouse, rat, hamster, guinea pig, rabbit, goat, sheep, cat, dog, pig, cow, horse, monkey, non-human primate, or human. In certain embodiments, a subject is a human.

[0113] “Treatment” of an individual (e.g., a mammal, such as a human) or a cell is any type of intervention used to alter the natural course of the individual or cell. Treatment includes, but is not limited to, administration of a pharmaceutical composition, and may be performed either prophylactically or subsequent to the initiation of a pathologic event or contact with an etiologic agent.II. Peptide-oligonucleotides

[0114] Provided herein is an antisense oligomer comprising a non-natural chemical backbone and a targeting sequence 13 to 30 bases in length that is complementary to a target region within a pre-mRNA of human dynamin 2 (DNM2) gene represented by SEQ ID NO: 1, wherein the target region is within an exon internal region, an intron internal region, an intron-exon junction, or an exon-intron junction of the human DNM2 gene pre-mRNA.

[0115] In certain embodiments, the target region is within an exon internal region of the human DNM2 gene pre-mRNA selected from exon 2 (SEQ ID NO: 2), exon 6 (SEQ ID NO: 3), exon 7 (SEQ ID NO: 4), exon 8 (SEQ ID NO: 5), exon 9 (SEQ ID NO: 6), exon 12 (SEQ ID NO: 7), exon 13 (SEQ ID NO: 8), exon 16 (SEQ ID NO: 9), and exon 19 (SEQ ID NO: 10).

[0116] In certain embodiments, the target region is within an exon internal region of the human DNM2 gene pre-mRNA selected from exon 2 (SEQ ID NO: 2), exon 9 (SEQ ID NO: 6), exon 12 (SEQ ID NO: 7), and exon 13 (SEQ ID NO: 8). In certain embodiments, the target region within an exon internal region of the human DNM2 gene pre-mRNA is exon 2 (SEQ ID NO: 2). In certain embodiments, the target region within an exon internal region of the human DNM2 gene pre-mRNA is exon 9 (SEQ ID NO: 6). In certain embodiments, the target region within an exon internal region of the human DNM2 gene pre-mRNA is exon 12 (SEQ ID NO: 7). In certain embodiments, the target region within an exon internal region of the human DNM2 gene pre- mRNA and exon 13 (SEQ ID NO: 8).

[0117] In certain embodiments, the target region is within an intron-exon junction or an exon- intron junction region of the human DNM2 gene pre-mRNA selected from intron 1 / exon 2 junction, exon 2 / intron 2 junction, intron 5 / exon 6 junction, exon 6 / intron 6 junction, intron 6 / exon 7 junction, exon 7 / intron 7 junction, intron 7 / exon 8 junction, exon 8 / intron 8 junction, intron 8 / exon 9 junction, exon 9 / intron 9 junction, intron 11 / exon 12 junction, exon 12 / intron 12 junction, intron 12 / exon 13 junction, exon 13 / intron 13 junction, intron 15 / exon 16 junction, exon 16 / intron 16 junction, intron 18 / exon 19 junction, and exon 19 / intron 19 junction.

[0118] In certain embodiments, the target region is within an intron-exon junction or an exon- intron junction of the human DNM2 gene pre-mRNA selected from intron 1 / exon 2 junction, exon 2 / intron 2 junction, intron 8 / exon 9 junction, exon 9 / intron 9 junction, intron 11 / exon 12 junction, exon 12 / intron 12 junction, intron 12 / exon 13 junction, and exon 13 / intron 13 junction.

[0119] In certain embodiments, the target region within an intron-exon junction or an exon-intron junction of the human DNM2 gene pre-mRNA is intron 1 / exon 2 junction. In certain embodiments, the target region within an intron-exon junction or an exon-intron junction of the human DNM2 gene pre-mRNA is exon 2 / intron 2 junction. In certain embodiments, the target region within an intron-exon junction or an exon-intron junction of the human DNM2 gene pre-mRNA is intron 8 / exon 9 junction. In certain embodiments, the target region within an intron- exon junction or an exon-intron junction of the human DNM2 gene pre-mRNA is exon 9 / intron 9 junction. In certain embodiments, the target region within an intron-exon junction or an exon- intron junction of the human DNM2 gene pre-mRNA is intron 11 / exon 12 junction. In certain embodiments, the target region within an intron-exon junction or an exon-intron junction of the human DNM2 gene pre-mRNA is exon 12 / intron 12 junction, intron 12 / exon 13 junction. In certain embodiments, the target region within an intron-exon junction or an exon-intron junction of the human DNM2 gene pre-mRNA is exon 13 / intron 13 junction.

[0120] In certain embodiments, the target region is within an intron internal region of the human DNM2 gene pre-mRNA selected from intron 2 (SEQ ID NO: 11) and intron 12 (SEQ ID NO: 12). In certain embodiments, the target region within an intron internal region of the human DNM2 gene pre-mRNA is intron 2 (SEQ ID NO: 11). In certain embodiments, the target region within an intron internal region of the human DNM2 gene pre-mRNA is intron 12 (SEQ ID NO: 12).

[0121] In certain embodiments, the antisense oligomer is 13-30 subunits in length. In certain embodiments, the antisense oligonucleotide is 13-30, 14-30, 15-30, 16-30, 17-30, 18-30, 19-30, 20-30, 21-30, 22-30, 23-30, 24-30, 25-30, 26-30, 27-30, 28-30, or 29-30 subunits in length.

[0122] In certain embodiments, the antisense oligomer is 13-29 subunits in length. In certain embodiments, the antisense oligonucleotide is 13-29, 14-29, 15-29, 16-29, 17-29, 18-29, 19-29, 20-29, 21-29, 22-29, 23-29, 24-29, 25-29, 26-29, 27-29, or 28-29 subunits in length.

[0123] In certain embodiments, the antisense oligomer is 13-28 subunits in length. In certain embodiments, the antisense oligonucleotide is 13-28, 14-28, 15-28, 16-28, 17-28, 18-28, 19-28, 20-28, 21-28, 22-28, 23-28, 24-28, 25-28, 26-28, or 27-28 subunits in length.

[0124] In certain embodiments, the antisense oligomer is 13-27 subunits in length. In certain embodiments, the antisense oligonucleotide is 13-27, 14-27, 15-27, 16-27, 17-27, 18-27, 19-27, 20-27, 21-27, 22-27, 23-27, 24-27, 25-27, or 26-27 subunits in length.

[0125] In certain embodiments, the antisense oligomer is 13-26 subunits in length. In certain embodiments, the antisense oligonucleotide is 13-26, 14-26, 15-26, 16-26, 17-26, 18-26, 19-26, 20-26, 21-26, 22-26, 23-26, 24-26, or 25-26 subunits in length.

[0126] In certain embodiments, the antisense oligomer is 13-25 subunits in length. In certain embodiments, the antisense oligonucleotide is 13-25, 14-25, 15-25, 16-25, 17-25, 18-25, 19-25, 20-25, 21-25, 22-25, 23-25, or 24-25 subunits in length.

[0127] In certain embodiments, the antisense oligomer is 13-24 subunits in length. In certain embodiments, the antisense oligonucleotide is 13-24, 14-24, 15-24, 16-24, 17-24, 18-24, 19-24, 20-24, 21-24, 22-24, or 23-24 subunits in length.

[0128] In certain embodiments, the antisense oligomer is 13-23 subunits in length. In certain embodiments, the antisense oligonucleotide is 13-23, 14-23, 15-23, 16-23, 17-23, 18-23, 19-23, 20-23, 21-23, or 22-23 subunits in length.

[0129] In certain embodiments, the antisense oligomer is 13-22 subunits in length. In certain embodiments, the antisense oligonucleotide is 13-22, 14-22, 15-22, 16-22, 17-22, 18-22, 19-22, 20-22, or 21-22 subunits in length.

[0130] In certain embodiments, the antisense oligomer is 13-21 subunits in length. In certain embodiments, the antisense oligonucleotide is 13-21, 14-21, 15-21, 16-21, 17-21, 18-21, 19-21, or 20-21 subunits in length.

[0131] In certain embodiments, the antisense oligomer is 13-20 subunits in length. In certain embodiments, the antisense oligonucleotide is 13-20, 14-20, 15-20, 16-20, 17-20, 18-20, or 19- 20 subunits in length.

[0132] In certain embodiments, the antisense oligomer is 13-19 subunits in length. In certain embodiments, the antisense oligonucleotide is 13-19, 14-19, 15-19, 16-19, 17-19, or 18-19 subunits in length.

[0133] In certain embodiments, the antisense oligomer is 13-18 subunits in length. In certain embodiments, the antisense oligonucleotide is 13-18, 14-18, 15-18, 16-18, or 17-18 subunits in length.

[0134] In certain embodiments, the antisense oligonucleotide is 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, or 30 subunits in length. In certain embodiments, the antisense oligonucleotide is 13 subunits in length. In certain embodiments, the antisense oligonucleotide is 14 subunits in length. In certain embodiments, the antisense oligonucleotide is 15 subunits in length. In certain embodiments, the antisense oligonucleotide is 16 subunits in length. In certain embodiments, the antisense oligonucleotide is 17 subunits in length. In certain embodiments, the antisense oligonucleotide is 18 subunits in length. In certain embodiments, the antisense oligonucleotide is 19 subunits in length. In certain embodiments, the antisense oligonucleotide is 20 subunits in length. In certain embodiments, the antisense oligonucleotide is 21 subunits in length. In certain embodiments, the antisense oligonucleotide is 22 subunits in length. In certain embodiments, the antisense oligonucleotide is 23 subunits in length. In certain embodiments, the antisense oligonucleotide is 24 subunits in length. In certain embodiments, the antisense oligonucleotide is 25 subunits in length. In certain embodiments, the antisense oligonucleotide is 26 subunits in length. In certain embodiments, the antisense oligonucleotide is 27 subunits in length. In certain embodiments, the antisense oligonucleotide is 28 subunits in length. In certain embodiments, the antisense oligonucleotide is 29 subunits in length. In certain embodiments, the antisense oligonucleotide is 30 subunits in length.

[0135] In certain embodiments, the target region of the human DNM2 gene pre-mRNA is DNM2 H2A (-10+15), DNM2 H2A(-7+17), DNM2 H2A(+3+27), DNM2 H2A(+15+37), DNM2 H2A(+21+45), DNM2 H2A(+23+47), DNM2 H2A(+27+51), DNM2 H2A(+37+61), DNM2 H2A(+46+70), DNM2 H2A (+48+72), DNM2 H2D(+20-5), DNM2 H2D (+13-12), DNM2 H2D(+12- 13), DNM2 H2D(+11-14), DNM2 H2D(+10-15), DNM2 H2D(+9-16), DNM2 H2D(+8-17), DNM2 H2D(+7-18), DNM2 H2D(+6-19), DNM2 H2D(+5-20), DNM2 H2D(+4-21), DNM2 H2D(+3-22), DNM2 H2D(+2-23), DNM2 H2D(+1-24), DNM2 H2D(-1-25), DNM2 H2D(-2-26), DNM2 H2D(-3- 27), DNM2 H2D(-4-28), DNM2 H2D(-5-29), DNM2 H2D(-6-30), DNM2 H9A(-12+13), DNM2 H9A(-5+20), DNM2 H9A(+1+25),DNM2 H9A(+6+30), DNM2 H9A(+16+40), DNM2 H9A(+25+49), DNM2 H9A(+36+60), DNM2 H9A(+37+61), DNM2 H9A(+42+66), DNM2 H9A(+43+62), DNM2 H9A(+43+63), DNM2 H9A(+43+64), DNM2 H9A(+43+65), DNM2 H9A(+43+66), DNM2 H9A(+43+67), DNM2 H9A(+44+67), DNM2 H9A(+44+68), DNM2 H9A(+45+67), DNM2 H9A (+46+67), DNM2 H9A(+47+67), DNM2 H9A(+48+67), DNM2 H9D(+24-1), DNM2 H9D(+23-2), DNM2 H9D(+22-3), DNM2 H9D(+21-4), DNM2 H9D(+20-5), DNM2 H9D(+19-6), DNM2 H9D (+18-7), DNM2 H9D(+17-8), DNM2 H9D(+16-9), DNM2 H9D(+15-10), DNM2 H9D(+14-11), DNM2 H9D(+13-12), DNM2 H9D(+12-13), DNM2 H9D(+11- 14), DNM2 H9D(+10-15), DNM2 H9D(+9-16), DNM2 H9D(+8-12), DNM2 H9D(+8-13), DNM2 H9D(+8-14), DNM2 H9D(+8-15), DNM2 H9D(+8-17), DNM2 H9D(+7-18), DNM2 H9D(+7-17), DNM2 H9D(+6-19), DNM2 H9D(+6-17), DNM2 H9D(+5-17), DNM2 H9D(+5-20), DNM2 H9D(+4- 17), DNM2 H9D(+4-21), DNM2 H9D(+3-17), DNM2 H9D(+3-22), DNM2 H12A(-13+12), DNM2 H12A(-3+22), DNM2 H12A(+4+28), DNM2 H12A(+7+31), DNM2 H12A(+10+34), DNM2 H12A(+11+35), DNM2 H12A(+12+36), DNM2 H12A(+13+37), DNM2 H12A(+14+38), DNM2 H12A(+15+39), DNM2 H12A(+16+40), DNM2 H12A(+17+41), DNM2 H12A(+18+42), DNM2 H12A(+19+43), DNM2 H12A(+20+44), DNM2 H12A(+25+44), DNM2 H12A(+25+45), DNM2 H12A(+25+46), DNM2 H12A(+25+47), DNM2 H12A(+25+48), DNM2 H12A(+25+49), DNM2 H12A(+26+49), DNM2 H12A(+27+49), DNM2 H12A(+28+49), DNM2 H12A(+29+49), DNM2 H12A(+29+53), DNM2 H12A(+30+49), DNM2 H12A(+30+54), DNM2 H12A(+36+60), DNM2 H12A(+37+61), DNM2 H12A(+43+67), DNM2 H12D(+22-3), DNM2 H12D(+20-5), DNM2 H12D(+15-10), DNM2 H12A(+4+28), DNM2 H12A(+7+31), DNM2 H12A(+10+34), DNM2 H12A(+11+35), DNM2 H12A(+12+36), DNM2 H12A(+13+37), DNM2 H12A(+14+38), DNM2 H12A(+15+39), DNM2 H12A(+16+40), DNM2 H12A(+17+41), DNM2 H12A(+18+42), DNM2 H12A(+19+43), DNM2 H12A(+20+44), DNM2 H12A(+25+44), DNM2 H12A(+25+45), DNM2 H12A(+25+46), DNM2 H12A(+25+47), DNM2 H12A(+25+48), DNM2 H12A(+25+49), DNM2 H12A(+26+49), DNM2 H12A(+27+49), DNM2 H12A(+28+49), DNM2 H12A(+29+49), DNM2 H12A(+29+53), DNM2 H12A(+30+49), DNM2 H12A(+30+54), DNM2 H12A(+36+60), DNM2H12A(+37+61), DNM2 H12A(+43+67), DNM2 H13A(-27-3), DNM2 H13A(-26-2), DNM2 H13A(- 25-1), DNM2 H13A(-24+1), DNM2 H13A(-23+2), DNM2 H13A(-22+3), DNM2 H13A(-21+4), DNM2 H13A(-20+5), DNM2 H13A(-19+6), DNM2 H13A(-18+7), DNM2 H13A(-17+8), DNM2 H13A(-16+9), DNM2 H13A(-15+10), DNM2 H13A(-14+11), DNM2 H13A(-13+12), DNM2 H13A(- 11+14), DNM2 H13A(-10+15), DNM2 H13A(-9+16), DNM2 H13A(-8+17), DNM2 H13A(-7+18), DNM2 H13A(-6+19), DNM2 H13A(-5+20), DNM2 H13A(-4+21), DNM2 H13A(-3+22), DNM2 H13A(-2+23), DNM2 H13A(-1+24), DNM2 H13A(+1+25), DNM2 H13A(+2+25), DNM2 H13A(+3+27), DNM2 H13A(+4+23), DNM2 H13A(+4+24), DNM2 H13A(+4+25), DNM2 H13A(+4+26), DNM2 H13A(+4+27), DNM2 H13A(+4+28), DNM2 H13A(+5+28), DNM2 H13A(+6+28), DNM2 H13A(+6+30), DNM2 H13A(+7+28), DNM2 H13A(+8+28), DNM2 H13A(+9+28), DNM2 H13A(+16+40), DNM2 H13D(+22-3), or DNM2 H13D(+7-18).

[0136] In certain embodiments, the target region is DNM2 H2A (-10+15). In certain embodiments, the target region is DNM2 H2A(-7+17). In certain embodiments, the target region is DNM2 H2A(+3+27). In certain embodiments, the target region is DNM2 H2A(+15+37). In certain embodiments, the target region is DNM2 H2A(+21+45). In certain embodiments, the target region is DNM2 H2A(+23+47). In certain embodiments, the target region is DNM2 H2A(+27+51). In certain embodiments, the target region is DNM2 H2A(+37+61). In certain embodiments, the target region is DNM2 H2A(+46+70). In certain embodiments, the target region is DNM2 H2A (+48+72). In certain embodiments, the target region is DNM2 H2D(+20-5). In certain embodiments, the target region is DNM2 H2D (+13-12). In certain embodiments, the target region is DNM2 H2D(+12-13). In certain embodiments, the target region is DNM2 H2D(+11-14). In certain embodiments, the target region is DNM2 H2D(+10-15). In certain embodiments, the target region is DNM2 H2D(+9-16). In certain embodiments, the target region is DNM2 H2D(+8-17). In certain embodiments, the target region is DNM2 H2D(+7-18). In certain embodiments, the target region is DNM2 H2D(+6-19). In certain embodiments, the target region is DNM2 H2D(+5-20). In certain embodiments, the target region is DNM2 H2D(+4-21). In certain embodiments, the target region is DNM2 H2D(+3-22). In certain embodiments, the target region is DNM2 H2D(+2-23) . In certain embodiments, the target region is DNM2 H2D(+1-24). In certain embodiments, the target region is DNM2 H2D(-1-25). In certain embodiments, the target region is DNM2 H2D(-2-26). In certain embodiments, the target region is DNM2 H2D(-3-27). In certain embodiments, the target region is DNM2 H2D(-4-28). In certain embodiments, the target region is DNM2 H2D(-5-29). In certain embodiments, the target region is DNM2 H2D(-6-30). In certain embodiments, the target region is DNM2 H6A(-20+5). In certain embodiments, the target region is DNM2 H6A(-6+19). In certain embodiments, the target region is DNM2 H6A(-2+23). In certain embodiments, the target region is DNM2 H6A(+3+26). In certain embodiments, thetarget region is DNM2 H6A(+10+3). In certain embodiments, the target region is DNM2 H6A(+13+37). In certain embodiments, the target region is DNM2 H6A(+23+47). In certain embodiments, the target region is DNM2 H6A(+32+56). In certain embodiments, the target region is DNM2 H6A(+35+59). In certain embodiments, the target region is DNM2 H6A(+44+68). In certain embodiments, the target region is DNM2 H6A(+54+78). In certain embodiments, the target region is DNM2 H6A(+60+84). In certain embodiments, the target region is DNM2 H6A(+63+87). In certain embodiments, the target region is DNM2 H6A(+88+112). In certain embodiments, the target region is DNM2 H6A(+96+119). In certain embodiments, the target region is DNM2 H6A(+105+129). In certain embodiments, the target region is DNM2 H6A(+121+145). In certain embodiments, the target region is DNM2 H6A(+130+154). In certain embodiments, the target region is DNM2 H6A(+132+156). In certain embodiments, the target region is DNM2 H6D (+6-19). In certain embodiments, the target region is DNM2 H6D (+15-10). In certain embodiments, the target region is DNM2 H6D (+17-8). In certain embodiments, the target region is DNM2 H7A(-15+10). In certain embodiments, the target region is DNM2 H7A(- 5+20). In certain embodiments, the target region is DNM2 H7A(+1+25). In certain embodiments, the target region is DNM2 H7A(+6+30). In certain embodiments, the target region is. In certain embodiments, the target region is DNM2 H7A(+22+46). In certain embodiments, the target region is DNM2 H7A(+29+53). In certain embodiments, the target region is DNM2 H7A(+41+65). In certain embodiments, the target region is DNM2 H7A(+51+75). In certain embodiments, the target region is DNM2 H7A(+57+81). In certain embodiments, the target region is DNM2 H7A(+62+86). In certain embodiments, the target region is DNM2 H7A(+72+96). In certain embodiments, the target region is DNM2 H7A(+74+98). In certain embodiments, the target region is DNM2 H7A(+81+105). In certain embodiments, the target region is DNM2 H7A(+91+115). In certain embodiments, the target region is DNM2 H7A(+110+134). In certain embodiments, the target region is DNM2 H7D(+8-16). In certain embodiments, the target region is DNM2 H7D(+9-16). In certain embodiments, the target region is DNM2 H7D(+21-4). In certain embodiments, the target region is DNM2 H8A(-20+5). In certain embodiments, the target region is DNM2 H8A(-14+11). In certain embodiments, the target region is DNM2 H8A(-7+18). In certain embodiments, the target region is DNM2 H8A(-6+19). In certain embodiments, the target region is DNM2 H8A(-2+23). In certain embodiments, the target region is DNM2 H8A(+5+29). In certain embodiments, the target region is DNM2 H8A(+18+42). In certain embodiments, the target region is DNM2 H8A(+21+45). In certain embodiments, the target region is DNM2 H8A(+27+51). In certain embodiments, the target region is DNM2 H8A(+36+60). In certain embodiments, the target region is DNM2 H8A(+46+70). In certain embodiments, the target region is DNM2 H8A(+51+75). In certain embodiments, the target region is DNM2 H8A(+56+80).In certain embodiments, the target region is DNM2 H8A(+65+88). In certain embodiments, the target region is DNM2 H8A(+76+100). In certain embodiments, the target region is DNM2 H8A(+83+107). In certain embodiments, the target region is DNM2 H8A(+96+119). In certain embodiments, the target region is DNM2 H8A(+105+129). In certain embodiments, the target region is DNM2 H8D(+18-7). In certain embodiments, the target region is DNM2 H8D(+10-15). In certain embodiments, the target region is DNM2 H9A(-12+13). In certain embodiments, the target region is DNM2 H9A(-5+20). In certain embodiments, the target region is DNM2 H9A(+1+25). In certain embodiments, the target region is DNM2 H9A(+6+30). In certain embodiments, the target region is DNM2 H9A(+16+40). In certain embodiments, the target region is DNM2 H9A(+25+49). In certain embodiments, the target region is DNM2 H9A(+36+60). In certain embodiments, the target region is DNM2 H9A(+37+61). In certain embodiments, the target region is DNM2 H9A(+42+66). In certain embodiments, the target region is DNM2 H9A(+43+62). In certain embodiments, the target region is DNM2 H9A(+43+63). In certain embodiments, the target region is DNM2 H9A(+43+64). In certain embodiments, the target region is DNM2 H9A(+43+65). In certain embodiments, the target region is DNM2 H9A(+43+66). In certain embodiments, the target region is DNM2 H9A(+43+67). In certain embodiments, the target region is DNM2 H9A(+44+67). In certain embodiments, the target region is DNM2 H9A(+44+68). In certain embodiments, the target region is DNM2 H9A(+45+67). In certain embodiments, the target region is DNM2 H9A (+46+67). In certain embodiments, the target region is DNM2 H9A(+47+67). In certain embodiments, the target region is DNM2 H9A(+48+67). In certain embodiments, the target region is DNM2 H9D(+24-1). In certain embodiments, the target region is DNM2 H9D(+23-2). In certain embodiments, the target region is DNM2 H9D(+22-3). In certain embodiments, the target region is DNM2 H9D(+21-4). In certain embodiments, the target region is DNM2 H9D(+20-5). In certain embodiments, the target region is DNM2 H9D(+19-6). In certain embodiments, the target region is DNM2 H9D (+18-7). In certain embodiments, the target region is DNM2 H9D(+17-8). In certain embodiments, the target region is DNM2 H9D(+16-9). In certain embodiments, the target region is DNM2 H9D(+15-10). In certain embodiments, the target region is DNM2 H9D(+14-11). In certain embodiments, the target region is DNM2 H9D(+13-12). In certain embodiments, the target region is DNM2 H9D(+12-13). In certain embodiments, the target region is DNM2 H9D(+11-14). In certain embodiments, the target region is DNM2 H9D(+10-15). In certain embodiments, the target region is DNM2 H9D(+9-16). In certain embodiments, the target region is DNM2 H9D(+8-12). In certain embodiments, the target region is DNM2 H9D(+8-13). In certain embodiments, the target region is DNM2 H9D(+8-14). In certain embodiments, the target region is DNM2 H9D(+8-15). In certain embodiments, the target region is DNM2 H9D(+8-17). In certain embodiments, the targetregion is DNM2 H9D(+7-18). In certain embodiments, the target region is DNM2 H9D(+7-17). In certain embodiments, the target region is DNM2 H9D(+6-19). In certain embodiments, the target region is DNM2 H9D(+6-17). In certain embodiments, the target region is DNM2 H9D(+5-17). In certain embodiments, the target region is DNM2 H9D(+5-20). In certain embodiments, the target region is DNM2 H9D(+4-17). In certain embodiments, the target region is DNM2 H9D(+4-21). In certain embodiments, the target region is DNM2 H9D(+3-17). In certain embodiments, the target region is DNM2 H9D(+3-22). In certain embodiments, the target region is DNM2 H12A(-13+12). In certain embodiments, the target region is DNM2 H12A(-3+22). In certain embodiments, the target region is DNM2 H12A(+4+28). In certain embodiments, the target region is DNM2 H12A(+7+31). In certain embodiments, the target region is DNM2 H12A(+10+34). In certain embodiments, the target region is DNM2 H12A(+11+35). In certain embodiments, the target region is DNM2 H12A(+12+36). In certain embodiments, the target region is DNM2 H12A(+13+37). In certain embodiments, the target region is DNM2 H12A(+14+38). In certain embodiments, the target region is DNM2 H12A(+15+39). In certain embodiments, the target region is DNM2 H12A(+16+40). In certain embodiments, the target region is DNM2 H12A(+17+41). In certain embodiments, the target region is DNM2 H12A(+18+42). In certain embodiments, the target region is DNM2 H12A(+19+43). In certain embodiments, the target region is DNM2 H12A(+20+44). In certain embodiments, the target region is DNM2 H12A(+25+44). In certain embodiments, the target region is DNM2 H12A(+25+45). In certain embodiments, the target region is DNM2 H12A(+25+46). In certain embodiments, the target region is DNM2 H12A(+25+47). In certain embodiments, the target region is DNM2 H12A(+25+48). In certain embodiments, the target region is DNM2 H12A(+25+49). In certain embodiments, the target region is DNM2 H12A(+26+49). In certain embodiments, the target region is DNM2 H12A(+27+49). In certain embodiments, the target region is DNM2 H12A(+28+49). In certain embodiments, the target region is DNM2 H12A(+29+49). In certain embodiments, the target region is DNM2 H12A(+29+53). In certain embodiments, the target region is DNM2 H12A(+30+49). In certain embodiments, the target region is DNM2 H12A(+30+54). In certain embodiments, the target region is DNM2 H12A(+36+60). In certain embodiments, the target region is DNM2 H12A(+37+61). In certain embodiments, the target region is DNM2 H12A(+43+67). In certain embodiments, the target region is DNM2 H12D(+22- 3). In certain embodiments, the target region is DNM2 H12D(+20-5). In certain embodiments, the target region is DNM2 H12D(+15-10). In certain embodiments, the target region is DNM2 H13A(-27-3). In certain embodiments, the target region is DNM2 H13A(-26-2). In certain embodiments, the target region is DNM2 H13A(-25-1). In certain embodiments, the target region is DNM2 H13A(-24+1). In certain embodiments, the target region is DNM2 H13A(-23+2). Incertain embodiments, the target region is DNM2 H13A(-22+3). In certain embodiments, the target region is DNM2 H13A(-21+4). In certain embodiments, the target region is DNM2 H13A(- 20+5). In certain embodiments, the target region is DNM2 H13A(-19+6). In certain embodiments, the target region is DNM2 H13A(-18+7). In certain embodiments, the target region is DNM2 H13A(-17+8). In certain embodiments, the target region is DNM2 H13A(-16+9). In certain embodiments, the target region is DNM2 H13A(-15+10). In certain embodiments, the target region is DNM2 H13A(-14+11). In certain embodiments, the target region is DNM2 H13A(- 13+12). In certain embodiments, the target region is DNM2 H13A(-11+14). In certain embodiments, the target region is DNM2 H13A(-10+15). In certain embodiments, the target region is DNM2 H13A(-9+16). In certain embodiments, the target region is DNM2 H13A(-8+17). In certain embodiments, the target region is DNM2 H13A(-7+18). In certain embodiments, the target region is DNM2 H13A(-6+19). In certain embodiments, the target region is DNM2 H13A(- 5+20). In certain embodiments, the target region is DNM2 H13A(-4+21). In certain embodiments, the target region is DNM2 H13A(-3+22). In certain embodiments, the target region is DNM2 H13A(-2+23). In certain embodiments, the target region is DNM2 H13A(-1+24). In certain embodiments, the target region is DNM2 H13A(+1+25). In certain embodiments, the target region is DNM2 H13A(+2+25). In certain embodiments, the target region is DNM2 H13A(+3+27). In certain embodiments, the target region is DNM2 H13A(+4+23). In certain embodiments, the target region is DNM2 H13A(+4+24). In certain embodiments, the target region is DNM2 H13A(+4+25). In certain embodiments, the target region is DNM2 H13A(+4+26). In certain embodiments, the target region is DNM2 H13A(+4+27). In certain embodiments, the target region is DNM2 H13A(+4+28). In certain embodiments, the target region is DNM2 H13A(+5+28). In certain embodiments, the target region is DNM2 H13A(+6+28). In certain embodiments, the target region is DNM2 H13A(+6+30). In certain embodiments, the target region is DNM2 H13A(+7+28). In certain embodiments, the target region is DNM2 H13A(+8+28). In certain embodiments, the target region is DNM2 H13A(+9+28). In certain embodiments, the target region is DNM2 H13A(+16+40). In certain embodiments, the target region is DNM2 H13D(+22-3). In certain embodiments, the target region is DNM2 H13D(+7-18). In certain embodiments, the target region is DNM2 H16A(-21+3). In certain embodiments, the target region is DNM2 H16A(-13+12). In certain embodiments, the target region is DNM2 H16A(- 6+19). In certain embodiments, the target region is DNM2 H16A(+6+30). In certain embodiments, the target region is DNM2 H16A(+15+39). In certain embodiments, the target region is DNM2 H16A(+26+50). In certain embodiments, the target region is DNM2 H16A(+36+60). In certain embodiments, the target region is DNM2 H16A(+45+69). In certain embodiments, the target region is DNM2 H16A(+55+79). In certain embodiments, the targetregion is DNM2 H16A(+66+90). In certain embodiments, the target region is DNM2 H16A(+75+99). In certain embodiments, the target region is DNM2 H16A(+82+106). In certain embodiments, the target region is DNM2 H16D(+19-6). In certain embodiments, the target region is DNM2 H16D(+11-14). In certain embodiments, the target region is DNM2 H19A(- 11+14). In certain embodiments, the target region is DNM2 H19A(-4+21). In certain embodiments, the target region is DNM2 H19A(+1+25). In certain embodiments, the target region is DNM2 H19A(+7+31). In certain embodiments, the target region is DNM2 H19A(+16+40). In certain embodiments, the target region is DNM2 H19A(+26+50). In certain embodiments, the target region is DNM2 H19A(+37+61). In certain embodiments, the target region is DNM2 H19A(+47+71). In certain embodiments, the target region is DNM2 H19A(+56+80). In certain embodiments, the target region is DNM2 H19A(+66+90). In certain embodiments, the target region is DNM2 H19A(+76+100). In certain embodiments, the target region is DNM2 H19A(+86+110). In certain embodiments, the target region is DNM2 H19A(+96+120). In certain embodiments, the target region is DNM2 H19A(+106+130). In certain embodiments, the target region is DNM2 H19A(+117+141). In certain embodiments, the target region is DNM2 H19A(+127+151). In certain embodiments, the target region is DNM2 H19A(+137+161). In certain embodiments, the target region is DNM2 H19A(+147+171). In certain embodiments, the target region is DNM2 H19A(+157+181). In certain embodiments, the target region is DNM2 H19A(+166+189). In certain embodiments, the target region is DNM2 H19A(+191+215). In certain embodiments, the target region is DNM2 H19A(+200+224). In certain embodiments, the target region is DNM2 H19D(+23-2). In certain embodiments, the target region is DNM2 H19D(+17-8). In certain embodiments, the target region is DNM2 H19D(+10-15).

[0137] In certain embodiments, the targeting sequence is selected from: SEQ ID NO: 67 (CGGGGAAGGAAGTCCCTGTGAGGGG); SEQ ID NO: 68 (CGCGGBGAAGGAAGTCCCTGTGAG); SEQ ID NO: 69 (ATTCCTGAACCGCGBGGAAGGAAGT); SEQ ID NO: 70 (CCGGGTGACGATTCCTGAACCGC); SEQ ID NO: 71 (AGAGGCCGCCGGGTGACGATTCCTG); SEQ ID NO: 72 (TGAGAGGCCGCCGGGTGACGATTCC); SEQ ID NO: 73 (AGAATGAGAGGCCGCCGGGTGACGA); SEQ ID NO: 74 (GATGAGCTGCAGAATGAGAGGCCGC); SEQ ID NO: 75 (TTTTGAGAAGATGAGCTGCAGAATG); SEQ ID NO: 76 (GTTTTTGAGAAGATGAGCTGCAGAA); SEQ ID NO: 77 (TTTACCTGTTTTTGAGAAGATGAGC);SEQ ID NO: 78 (GCCCCATTTTACCTGTTTTTGAGAA); SEQ ID NO: 79 (CGCCCCATTTTACCTGTTTTTGAGA); SEQ ID NO: 80 (CCGCCCCATTTTACCTGTTTTTGAG); SEQ ID NO: 81 (GCCGCCCCATTTTACCTGTTTTTGA); SEQ ID NO: 82 (GGCCGCCCCATTTTACCTGTTTTTG); SEQ ID NO: 83 (AGGCCGCCCCATTTTACCTGTTTTT); SEQ ID NO: 84 (CAGGCCGCCCCATTTTACCTGTTTT); SEQ ID NO: 85 (TCAGGCCGCCCCATTTTACCTGTTT); SEQ ID NO: 86 (CTCAGGCCGCCCCATTTTACCTGTT); SEQ ID NO: 87 (CCTCAGGCCGCCCCATTTTACCTGT); SEQ ID NO: 88 (ACCTCAGGCCGCCCCATTTTACCTG); SEQ ID NO: 89 (AACCTCAGGCCGCCCCATTTTACCT); SEQ ID NO: 90 (GAACCTCAGGCCGCCCCATTTTACC); SEQ ID NO: 91 (TGAACCTCAGGCCGCCCCATTTTAC); SEQ ID NO: 92 (CTGAACCTCAGGCCGCCCCATTTTA); SEQ ID NO: 93 (GCTGAACCTCAGGCCGCCCCATTTT); SEQ ID NO: 94 (TGCTGAACCTCAGGCCGCCCCATTT); SEQ ID NO: 95 (CTGCTGAACCTCAGGCCGCCCCATT); SEQ ID NO: 96 (CCTGCTGAACCTCAGGCCGCCCCAT); SEQ ID NO: 97 (GTAGCCTGTGGGGAGAGGCAGTCAG); SEQ ID NO: 98 (TTCACCACGCCAATGTAGCCTGTGG); SEQ ID NO: 99 (GCGGTTCACCACGCCAATGTAGCCT); SEQ ID NO: 100 (GCTGCGGTTCACCACGCCAATGTA); SEQ ID NO: 101 (TCCTTCTGGCTGCGGTTCACCACGC); SEQ ID NO: 102 (ATATCCTTCTGGCTGCGGTTCACCA); SEQ ID NO: 103 (CTTGCCCTCAATATCCTTCTGGCTG); SEQ ID NO: 104 (GATGTCCTTCTTGCCCTCAATATCC); SEQ ID NO: 105 (ACGGATGTCCTTCTTGCCCTCAATA); SEQ ID NO: 106 (CAGTGCTGCACGGATGTCCTTCTTG); SEQ ID NO: 107 (TCTCAGCTGCCAGTGCTGCACGGAT); SEQ ID NO: 108 (ACTTCCTCTCAGCTGCCAGTGCTGC); SEQ ID NO: 109 (AGAACTTCCTCTCAGCTGCCAGTGC); SEQ ID NO: 110 (TGCCGGTAGGCCGGGTGGGAGAGGA); SEQ ID NO: 111 (GGCCATGTGCCGGTAGGCCGGGTG); SEQ ID NO: 112 (CCATGCGGTCGGCCATGTGCCGGTA);SEQ ID NO: 113 (TGCAGATGTGGCGTGCCCATGCGGT); SEQ ID NO: 114 (AGCGTCTTCTGCAGATGTGGCGTGC); SEQ ID NO: 115 (TCAGCGTCTTCTGCAGATGTGGCGT); SEQ ID NO: 116 (GTGCAAACCCTTGCAGTACCTGATT); SEQ ID NO: 117 (CTTGCAGTACCTGATTCAGCGTCTT); SEQ ID NO: 118 (TGCAGTACCTGATTCAGCGTCTTCT); SEQ ID NO: 119 (TGGTCAGTTGCTGCAGGAGAGAGGT); SEQ ID NO: 120 (CGGATGTGGTTGGTCAGTTGCTGCA); SEQ ID NO: 121 (ACTCCCGGATGTGGTTGGTCAGTTG); SEQ ID NO: 122 (CAGCGACTCCCGGATGTGGTTGGTC); SEQ ID NO: 123 (GCCGGCAGCGACTCCCGGATGTGGT); SEQ ID NO: 124 (TGCTACGTAGGGCCGGCAGCGACTC); SEQ ID NO: 125 (TGTAGTTTGCTACGTAGGGCCGGCA); SEQ ID NO: 126 (AGCAGCTGGCTCTGTAGTTTGCTAC); SEQ ID NO: 127 (CTCCAGGGACAGCAGCTGGCTCTGT); SEQ ID NO: 128 (CTCCTTCTCCAGGGACAGCAGCTGG); SEQ ID NO: 129 (TCCACCTCCTTCTCCAGGGACAGCA); SEQ ID NO: 130 (CTTGTACTCCTCCACCTCCTTCTCC); SEQ ID NO: 131 (TTCTTGTACTCCTCCACCTCCTTCT); SEQ ID NO: 132 (CCGAAAGTTCTTGTACTCCTCCACC); SEQ ID NO: 133 (GGTCGTCGGGCCGAAAGTTCTTGTA); SEQ ID NO: 134 (GCTTTGGTTTTGCGGGTGGGGTCGT); SEQ ID NO: 135 (GTGCCGBGGTACATACTGCAGCAG); SEQ ID NO: 136 (GTGCCGGGGTACATACTGCAGCAGG); SEQ ID NO: 137 (ATACTGCAGCAGGGCTTTGGTTTTG); SEQ ID NO: 138 (CCATCCTATGAGGAAAAGGAAAAAG); SEQ ID NO: 139 (GCTGGACCATCCTATGAGGAAAAGG); SEQ ID NO: 140 (CCAAACTGCTGGACCATCCTATGAG); SEQ ID NO: 141 (CCCAAACTGCTGGACCATCCTATGA); SEQ ID NO: 142 (CCACCCCAAACTGCTGGACCATCCT); SEQ ID NO: 143 (CAAAATCCACCCCAAACTGCTGGAC); SEQ ID NO: 144 (TCGATCCTCTTCTCAAAATCCACCC); SEQ ID NO: 145 (CCCTCGATCCTCTTCTCAAAATCCA); SEQ ID NO: 146 (CCTGAGCCCTCGATCCTCTTCTCAA); SEQ ID NO: 147 (ACCTGATCTCCTGAGCCCTCGATCC);SEQ ID NO: 148 (CAGAGTGTCCACCTGATCTCCTGAG); SEQ ID NO: 149 (AGCTCCAGAGTGTCCACCTGATCTC); SEQ ID NO: 150 (CGGAGAGCTCCAGAGTGTCCACCTG); SEQ ID NO: 151 (GGCGCCCCCGGAGAGCTCCAGAGT); SEQ ID NO: 152 (GCGATTGATTCGGGCGCCCCCGGAG); SEQ ID NO: 153 (GGAAGATGCGATTGATTCGGGCGCC); SEQ ID NO: 154 (GGAACCGCTCGTGGAAGATGCGAT); SEQ ID NO: 155 (AGCTCAAATGGGAACCGCTCGTGGA); SEQ ID NO: 156 (GCACTACCTTCACCAGCTCAAATGG); SEQ ID NO: 157 (CCCGGGGGGCACTACCTTCACCAGC); SEQ ID NO: 158 (CGTCAAACTCCATCTGAGAAGAGAC); SEQ ID NO: 159 (TCCTTCTCGTCAAACTCCATCTGAG); SEQ ID NO: 160 (GTAAGTCCTTCTCGTCAAACTCCAT); SEQ ID NO: 161 (CCGTCGTAAGTCCTTCTCGTCAAAC); SEQ ID NO: 162 (AGCTGATCTCCCGTCGTAAGTCCTT); SEQ ID NO: 163 (TAATGGCATAGCTGATCTCCCGTCG); SEQ ID NO: 164 (ATGGATGTTCTTAATGGCATAGCTG); SEQ ID NO: 165 (CATGGATGTTCTTAATGGCATAGCT); SEQ ID NO: 166 (GACTCCATGGATGTTCTTAATGGCA); SEQ ID NO: 167 (CCATGGATGTTCTTAATGGC); SEQ ID NO: 168 TCCATGGATGTTCTTAATGGC); SEQ ID NO: 169 (CTCCATGGATGTTCTTAATGGC); SEQ ID NO: 170 (ACTCCATGGATGTTCTTAATGGC); SEQ ID NO: 171 (GACTCCATGGATGTTCTTAATGGC); SEQ ID NO: 172 (TGACTCCATGGATGTTCTTAATGGC); SEQ ID NO: 173 (TGACTCCATGGATGTTCTTAATGG); SEQ ID NO: 174 (CTGACTCCATGGATGTTCTTAATGG); SEQ ID NO: 175 (TGACTCCATGGATGTTCTTAATG); SEQ ID NO: 176 (TGACTCCATGGATGTTCTTAAT); SEQ ID NO: 177 (TGACTCCATGGATGTTCTTAA); SEQ ID NO: 178 (TGACTCCATGGATGTTCTTA); SEQ ID NO: 179 (CCTGACTCCATGGATGTTCTTAATG); SEQ ID NO: 180 (GCCTGACTCCATGGATGTTCTTAAT); SEQ ID NO: 181 (TGCCTGACTCCATGGATGTTCTTAA); SEQ ID NO: 182 (TTGCCTGACTCCATGGATGTTCTTA);SEQ ID NO: 183 (CTTGCCTGACTCCATGGATGTTCTT); SEQ ID NO: 184 (ACTTGCCTGACTCCATGGATGTTCT); SEQ ID NO: 185 (AACTTGCCTGACTCCATGGATGTTC); SEQ ID NO: 186 (GAACTTGCCTGACTCCATGGATGTT); SEQ ID NO: 187 (GGAACTTGCCTGACTCCATGGATGT); SEQ ID NO: 188 TGGAACTTGCCTGACTCCATGGATG); SEQ ID NO: 189 (GTGGAACTTGCCTGACTCCATGGAT); SEQ ID NO: 190 (CGTGGAACTTGCCTGACTCCATGGA); SEQ ID NO: 191 TCGTGGAACTTGCCTGACTCCATGG); SEQ ID NO: 192 (CTCGTGGAACTTGCCTGACTCCATG); SEQ ID NO: 193 (CCTCGTGGAACTTGCCTGACTCCAT); SEQ ID NO: 194 (TCCTCGTGGAACTTGCCTGACTCCA); SEQ ID NO: 195 (TCCTCGTGGAACTTGCCTGACTCCA); SEQ ID NO: 196 (TCGTGGAACTTGCCTGACTCC); SEQ ID NO: 197 (CTCGTGGAACTTGCCTGACTCC); SEQ ID NO: 198 (CCTCGTGGAACTTGCCTGACTCC); SEQ ID NO: 199 (CTCCTCGTGGAACTTGCCTGACTCC); SEQ ID NO: 200 (TCTCCTCGTGGAACTTGCCTGACTC); SEQ ID NO: 201 (CTCCTCGTGGAACTTGCCTGACTC); SEQ ID NO: 202 (CTCTCCTCGTGGAACTTGCCTGACT); SEQ ID NO: 203 (CTCCTCGTGGAACTTGCCTGACT); SEQ ID NO: 204 (CTCCTCGTGGAACTTGCCTGAC); SEQ ID NO: 205 (ACTCTCCTCGTGGAACTTGCCTGAC); SEQ ID NO: 206 (CTCCTCGTGGAACTTGCCTGA); SEQ ID NO: 207 (GACTCTCCTCGTGGAACTTGCCTGA); SEQ ID NO: 208 (CTCCTCGTGGAACTTGCCTG); SEQ ID NO: 209 (TGACTCTCCTCGTGGAACTTGCCTG); SEQ ID NO: 210 (CAGCAGAAGAATCTGGBGGAGAGCG); SEQ ID NO: 211 (CAATGTCGATCAGCAGAAGAATCTG); SEQ ID NO: 212 (ACTGCTCAATGTCGATCAGCAGAAG); SEQ ID NO: 213 (AGGACTGCTCAATGTCGATCAGCAG); SEQ ID NO: 214 (TGTAGGACTGCTCAATGTCGATCAG); SEQ ID NO: 215 (ATGTAGGACTGCTCAATGTCGATCA); SEQ ID NO: 216 (GATGTAGGACTGCTCAATGTCGATC); SEQ ID NO: 217 (TGATGTAGGACTGCTCAATGTCGAT);SEQ ID NO: 218 (TTGATGTAGGACTGCTCAATGTCGA); SEQ ID NO: 219 (GTTGATGTAGGACTGCTCAATGTCG); SEQ ID NO: 220 (TGTTGATGTAGGACTGCTCAATGTC); SEQ ID NO: 221 (GTGTTGATGTAGGACTGCTCAATGT); SEQ ID NO: 222 (CGTGTTGATGTAGGACTGCTCAATG); SEQ ID NO: 223 (TCGTGTTGATGTAGGACTGCTCAAT); SEQ ID NO: 224 (TTCGTGTTGATGTAGGACTGCTCAA); SEQ ID NO: 225 (TTCGTGTTGATGTAGGACTG); SEQ ID NO: 226 (GTTCGTGTTGATGTAGGACTG); SEQ ID NO: 227 (GGTTCGTGTTGATGTAGGACTG); SEQ ID NO: 228 (TGGTTCGTGTTGATGTAGGACTG); SEQ ID NO: 229 (ATGGTTCGTGTTGATGTAGGACTG); SEQ ID NO: 230 (CATGGTTCGTGTTGATGTAGGACTG); SEQ ID NO: 231 (CATGGTTCGTGTTGATGTAGGACT); SEQ ID NO: 232 (CATGGTTCGTGTTGATGTAGGAC); SEQ ID NO: 233 (CATGGTTCGTGTTGATGTAGGA); SEQ ID NO: 234 (CATGGTTCGTGTTGATGTAGG); SEQ ID NO: 235 (TCCTCATGGTTCGTGTTGATGTAGG); SEQ ID NO: 236 (CATGGTTCGTGTTGATGTAG); SEQ ID NO: 237 (GTCCTCATGGTTCGTGTTGATGTAG); SEQ ID NO: 238 (GATGAAGTCCTCATGGTTCGTGTTG); SEQ ID NO: 239 (CGATGAAGTCCTCATGGTTCGTGTT); SEQ ID NO: 240 (CAAACCCGATGAAGTCCTCATGGTT); SEQ ID NO: 241 (TACTTGGCAAACCCGATGAAGTCCT); SEQ ID NO: 242 (CCTACTTGGCAAACCCGATGAAGTC); SEQ ID NO: 243 (AAGTACCTACTTGGCAAACCCGATG); SEQ ID NO: 244 (GAAACCAAAGAACAGACAGGGTTCA); SEQ ID NO: 245 (TGAAACCAAAGAACAGACAGGGTTC); SEQ ID NO: 246 (CTGAAACCAAAGAACAGACAGGGTT); SEQ ID NO: 247 (ACTGAAACCAAAGAACAGACAGGGT); SEQ ID NO: 248 (CACTGAAACCAAAGAACAGACAGGG); SEQ ID NO: 249 (GCACTGAAACCAAAGAACAGACAGG); SEQ ID NO: 250 (GGCACTGAAACCAAAGAACAGACAG); SEQ ID NO: 251 (GGGCACTGAAACCAAAGAACAGACA); SEQ ID NO: 252 (TGGGCACTGAAACCAAAGAACAGAC);SEQ ID NO: 253 (CTGGGCACTGAAACCAAAGAACAGA); SEQ ID NO: 254 (GCTGGGCACTGAAACCAAAGAACAG); SEQ ID NO: 255 (TGCTGGGCACTGAAACCAAAGAACA); SEQ ID NO: 256 (CTGCTGGGCACTGAAACCAAAGAAC); SEQ ID NO: 257 (TCTGCTGGGCACTGAAACCAAAGAA); SEQ ID NO: 258 (CTCTGCTGGGCACTGAAACCAAAGA); SEQ ID NO: 259 (TCCTCTGCTGGGCACTGAAACCAAA); SEQ ID NO: 260 (CTCCTCTGCTGGGCACTGAAACCAA); SEQ ID NO: 261 (GCTCCTCTGCTGGGCACTGAAACCA); SEQ ID NO: 262 (TGCTCCTCTGCTGGGCACTGAAACC); SEQ ID NO: 263 (GTGCTCCTCTGCTGGGCACTGAAAC); SEQ ID NO: 264 (CGTGCTCCTCTGCTGGGCACTGAAA); SEQ ID NO: 265 (GCGTGCTCCTCTGCTGGGCACTGAA); SEQ ID NO: 266 (TGCGTGCTCCTCTGCTGGGCACTGA); SEQ ID NO: 267 (CTGCGTGCTCCTCTGCTGGGCACTG); SEQ ID NO: 268 (GCTGCGTGCTCCTCTGCTGGGCACT); SEQ ID NO: 269 (AGCTGCGTGCTCCTCTGCTGGGCAC); SEQ ID NO: 270 (CAGCTGCGTGCTCCTCTGCTGGGCA); SEQ ID NO: 271 (TCAGCTGCGTGCTCCTCTGCTGGGC); SEQ ID NO: 272 (TTCAGCTGCGTGCTCCTCTGCTGGG); SEQ ID NO: 273 (GCTGCGTGCTCCTCTGCTGG); SEQ ID NO: 274 (AGCTGCGTGCTCCTCTGCTGG); SEQ ID NO: 275 (CAGCTGCGTGCTCCTCTGCTGG); SEQ ID NO: 276 (TCAGCTGCGTGCTCCTCTGCTGG); SEQ ID NO: 277 (TTCAGCTGCGTGCTCCTCTGCTGG); SEQ ID NO: 278 (GTTCAGCTGCGTGCTCCTCTGCTGG); SEQ ID NO: 279 (GTTCAGCTGCGTGCTCCTCTGCTG); SEQ ID NO: 280 (GTTCAGCTGCGTGCTCCTCTGCT); SEQ ID NO: 281 (TTGTTCAGCTGCGTGCTCCTCTGCT); SEQ ID NO: 282 (GTTCAGCTGCGTGCTCCTCTGC); SEQ ID NO: 283 (GTTCAGCTGCGTGCTCCTCTG); SEQ ID NO: 284 (GTTCAGCTGCGTGCTCCTCT); SEQ ID NO: 285 (GGCTCTCTTCTTGTTCAGCTGCGTG); SEQ ID NO: 286 (TACCTGATTGGBGATGGCTCTCTTC); SEQ ID NO: 287 (TGCAGAGGBGTGTGCTACCTGATTG);SEQ ID NO: 288 (CTCCTGAGGGTGGAGGGAAAAGAG); SEQ ID NO: 289 (CTTCTCTTTCTCCTGAGGGTGGAGG); SEQ ID NO: 290 (TGTACTTCTTCTCTTTCTCCTGAGG); SEQ ID NO: 291 (CAGAGGCAGCATGTACTTCTTCTCT); SEQ ID NO: 292 (GAGGTTGTCCAGAGGCAGCATGTAC); SEQ ID NO: 293 (TCACGGATCTTGAGGTTGTCCAGAG); SEQ ID NO: 294 (CTTCTCCACATCACGGATCTTGAGG); SEQ ID NO: 295 (CATGAAGCCCTTCTCCACATCACGG); SEQ ID NO: 296 (GCTTGTTGGACATGAAGCCCTTCTC); SEQ ID NO: 297 (GGCGAAGACGTGCTTGTTGGACATG); SEQ ID NO: 298 (GTTGAAGATGGCGAAGACGTGCTTG); SEQ ID NO: 299 (GCTCCGTGTTGAAGATGGCGAAGAC); SEQ ID NO: 300 (CCTCACCTCTGCTCCGTGTTGAAGA); SEQ ID NO: 301 (CCTGGGCCCCTCACCTCTGCTCCGT); SEQ ID NO: 302 (ATGAAGGCCTTCGTCTGCGGGCAGG); SEQ ID NO: 303 (GTGGTGGATGAAGGCCTTCGTCTGC); SEQ ID NO: 304 (GCTCGTGGTGGATGAAGGCCTTCGT); SEQ ID NO: 305 (CCAGCAGCTCGTGGTGGATGAAGGC); SEQ ID NO: 306 (ATAGGTAGGCCAGCAGCTCGTGGTG); SEQ ID NO: 307 (GCCGAGGAGTATAGGTAGGCCAGCA); SEQ ID NO: 308 (TGCTCTGGTCTGCCGAGGAGTATAG); SEQ ID NO: 309 (TCCATGAGGCTGCTCTGGTCTGCCG); SEQ ID NO: 310 (GCCGACTCCTCCATGAGGCTGCTCT); SEQ ID NO: 311 (TGCCTGGTCAGCCGACTCCTCCATG); SEQ ID NO: 312 (CCCGCCGCTGTGCCTGGTCAGCCGA); SEQ ID NO: 313 (AGCATGTCGTCCCGCCGCTGTGCCT); SEQ ID NO: 314 (GTACATGCGCAGCATGTCGTCCCGC); SEQ ID NO: 315 (TGAGGGCATGGTACATGCGCAGCAT); SEQ ID NO: 316 (GAGCGCCTCCTTGAGGGCATGGTAC); SEQ ID NO: 317 (CGATGATGTTGAGCGCCTCCTTGAG); SEQ ID NO: 318 (CTGATGTCACCGATGATGTTGAGCG); SEQ ID NO: 319 (AGTGCTGGTGCTGATGTCACCGATG); SEQ ID NO: 320 (GCGTGGACACAGTGCTGGTGCTGAT); SEQ ID NO: 321 (GGGTACAGGCGTGGACACAGTGCT); SEQ ID NO: 322 (TGGAGCCAGGTGTCATCGACAGGCG);SEQ ID NO: 323 (CTGGCGCTCTGGAGCCAGGTGTCAT); SEQ ID NO: 324 (ACCTGTGGCTGCTGGCGCTCTGGAG); SEQ ID NO: 325 (TTCCGGACCTGTGGCTGCTGGCGCT); and SEQ ID NO: 326 (ACCAGGCTTCCGGACCTGTGGCTGC), wherein “B” represents an abasic subunit or guanine. In certain embodiments, B is an abasic subunit.

[0138] In certain embodiments, the targeting sequence is SEQ ID NO: 67. In certain embodiments, the targeting sequence is SEQ ID NO: 68. In certain embodiments, the targeting sequence is SEQ ID NO: 69. In certain embodiments, the targeting sequence is SEQ ID NO: 70.

[0139] In certain embodiments, the targeting sequence is SEQ ID NO: 71. In certain embodiments, the targeting sequence is SEQ ID NO: 72. In certain embodiments, the targeting sequence is SEQ ID NO: 73. In certain embodiments, the targeting sequence is SEQ ID NO: 74. In certain embodiments, the targeting sequence is SEQ ID NO: 75. In certain embodiments, the targeting sequence is SEQ ID NO: 76. In certain embodiments, the targeting sequence is SEQ ID NO: 77. In certain embodiments, the targeting sequence is SEQ ID NO: 78. In certain embodiments, the targeting sequence is SEQ ID NO: 79. In certain embodiments, the targeting sequence is SEQ ID NO: 80. In certain embodiments, the targeting sequence is SEQ ID NO: 81. In certain embodiments, the targeting sequence is SEQ ID NO: 82. In certain embodiments, the targeting sequence is SEQ ID NO: 83. In certain embodiments, the targeting sequence is SEQ ID NO: 84. In certain embodiments, the targeting sequence is SEQ ID NO: 85. In certain embodiments, the targeting sequence is SEQ ID NO: 86. In certain embodiments, the targeting sequence is SEQ ID NO: 87. In certain embodiments, the targeting sequence is SEQ ID NO: 88. In certain embodiments, the targeting sequence is SEQ ID NO: 89. In certain embodiments, the targeting sequence is SEQ ID NO: 90. In certain embodiments, the targeting sequence is SEQ ID NO: 91. In certain embodiments, the targeting sequence is SEQ ID NO: 92. In certain embodiments, the targeting sequence is SEQ ID NO: 93. In certain embodiments, the targeting sequence is SEQ ID NO: 94. In certain embodiments, the targeting sequence is SEQ ID NO: 95. In certain embodiments, the targeting sequence is SEQ ID NO: 96. In certain embodiments, the targeting sequence is SEQ ID NO: 97. In certain embodiments, the targeting sequence is SEQ ID NO: 98. In certain embodiments, the targeting sequence is SEQ ID NO: 99. In certain embodiments, the targeting sequence is SEQ ID NO: 100. In certain embodiments, the targeting sequence is SEQ ID NO: 101. In certain embodiments, the targeting sequence is SEQ ID NO: 102. In certain embodiments, the targeting sequence is SEQ ID NO: 103. In certain embodiments, the targeting sequence is SEQ ID NO: 104. In certain embodiments, the targeting sequence is SEQ ID NO: 105. In certain embodiments, the targeting sequence is SEQ ID NO:106. In certain embodiments, the targeting sequence is SEQ ID NO: 107. In certain embodiments, the targeting sequence is SEQ ID NO: 108. In certain embodiments, the targeting sequence is SEQ ID NO: 109. In certain embodiments, the targeting sequence is SEQ ID NO: 110. In certain embodiments, the targeting sequence is SEQ ID NO: 111. In certain embodiments, the targeting sequence is SEQ ID NO: 112. In certain embodiments, the targeting sequence is SEQ ID NO: 113. In certain embodiments, the targeting sequence is SEQ ID NO: 114. In certain embodiments, the targeting sequence is SEQ ID NO: 115. In certain embodiments, the targeting sequence is SEQ ID NO: 116. In certain embodiments, the targeting sequence is SEQ ID NO: 117. In certain embodiments, the targeting sequence is SEQ ID NO: 118. In certain embodiments, the targeting sequence is SEQ ID NO: 119. In certain embodiments, the targeting sequence is SEQ ID NO: 120. In certain embodiments, the targeting sequence is SEQ ID NO: 121. In certain embodiments, the targeting sequence is SEQ ID NO: 122. In certain embodiments, the targeting sequence is SEQ ID NO: 123. In certain embodiments, the targeting sequence is SEQ ID NO: 124. In certain embodiments, the targeting sequence is SEQ ID NO: 125. In certain embodiments, the targeting sequence is SEQ ID NO: 126. In certain embodiments, the targeting sequence is SEQ ID NO: 127. In certain embodiments, the targeting sequence is SEQ ID NO: 128. In certain embodiments, the targeting sequence is SEQ ID NO: 129. In certain embodiments, the targeting sequence is SEQ ID NO: 130. In certain embodiments, the targeting sequence is SEQ ID NO: 131. In certain embodiments, the targeting sequence is SEQ ID NO: 132. In certain embodiments, the targeting sequence is SEQ ID NO: 133. In certain embodiments, the targeting sequence is SEQ ID NO: 134. In certain embodiments, the targeting sequence is SEQ ID NO: 135. In certain embodiments, the targeting sequence is SEQ ID NO: 136. In certain embodiments, the targeting sequence is SEQ ID NO: 137. In certain embodiments, the targeting sequence is SEQ ID NO: 138. In certain embodiments, the targeting sequence is SEQ ID NO: 139. In certain embodiments, the targeting sequence is SEQ ID NO: 140. In certain embodiments, the targeting sequence is SEQ ID NO: 141. In certain embodiments, the targeting sequence is SEQ ID NO: 142. In certain embodiments, the targeting sequence is SEQ ID NO: 143. In certain embodiments, the targeting sequence is SEQ ID NO: 144. In certain embodiments, the targeting sequence is SEQ ID NO: 145. In certain embodiments, the targeting sequence is SEQ ID NO: 146. In certain embodiments, the targeting sequence is SEQ ID NO: 147. In certain embodiments, the targeting sequence is SEQ ID NO: 148. In certain embodiments, the targeting sequence is SEQ ID NO: 149. In certain embodiments, the targeting sequence is SEQ ID NO: 150. In certain embodiments, the targeting sequence is SEQ ID NO: 151. In certain embodiments, the targeting sequence is SEQ ID NO: 152. In certain embodiments, the targetingsequence is SEQ ID NO: 153. In certain embodiments, the targeting sequence is SEQ ID NO: 154. In certain embodiments, the targeting sequence is SEQ ID NO: 155. In certain embodiments, the targeting sequence is SEQ ID NO: 156. In certain embodiments, the targeting sequence is SEQ ID NO: 157. In certain embodiments, the targeting sequence is SEQ ID NO: 158. In certain embodiments, the targeting sequence is SEQ ID NO: 159. In certain embodiments, the targeting sequence is SEQ ID NO: 160. In certain embodiments, the targeting sequence is SEQ ID NO: 161. In certain embodiments, the targeting sequence is SEQ ID NO: 162. In certain embodiments, the targeting sequence is SEQ ID NO: 163. In certain embodiments, the targeting sequence is SEQ ID NO: 164. In certain embodiments, the targeting sequence is SEQ ID NO: 165. In certain embodiments, the targeting sequence is SEQ ID NO: 166. In certain embodiments, the targeting sequence is SEQ ID NO: 167. In certain embodiments, the targeting sequence is SEQ ID NO: 168. In certain embodiments, the targeting sequence is SEQ ID NO: 169. In certain embodiments, the targeting sequence is SEQ ID NO: 170. In certain embodiments, the targeting sequence is SEQ ID NO: 171. In certain embodiments, the targeting sequence is SEQ ID NO: 172. In certain embodiments, the targeting sequence is SEQ ID NO: 173. In certain embodiments, the targeting sequence is SEQ ID NO: 174. In certain embodiments, the targeting sequence is SEQ ID NO: 175. In certain embodiments, the targeting sequence is SEQ ID NO: 176. In certain embodiments, the targeting sequence is SEQ ID NO: 177. In certain embodiments, the targeting sequence is SEQ ID NO: 178. In certain embodiments, the targeting sequence is SEQ ID NO: 179. In certain embodiments, the targeting sequence is SEQ ID NO: 180. In certain embodiments, the targeting sequence is SEQ ID NO: 181. In certain embodiments, the targeting sequence is SEQ ID NO: 182. In certain embodiments, the targeting sequence is SEQ ID NO: 183. In certain embodiments, the targeting sequence is SEQ ID NO: 184. In certain embodiments, the targeting sequence is SEQ ID NO: 185. In certain embodiments, the targeting sequence is SEQ ID NO: 186. In certain embodiments, the targeting sequence is SEQ ID NO: 187. In certain embodiments, the targeting sequence is SEQ ID NO: 188. In certain embodiments, the targeting sequence is SEQ ID NO: 189. In certain embodiments, the targeting sequence is SEQ ID NO: 190. In certain embodiments, the targeting sequence is SEQ ID NO: 191. In certain embodiments, the targeting sequence is SEQ ID NO: 192. In certain embodiments, the targeting sequence is SEQ ID NO: 193. In certain embodiments, the targeting sequence is SEQ ID NO: 194. In certain embodiments, the targeting sequence is SEQ ID NO: 195. In certain embodiments, the targeting sequence is SEQ ID NO: 196. In certain embodiments, the targeting sequence is SEQ ID NO: 197. In certain embodiments, the targeting sequence is SEQ ID NO: 198. In certain embodiments, the targeting sequence is SEQ ID NO: 199. In certainembodiments, the targeting sequence is SEQ ID NO: 200. In certain embodiments, the targeting sequence is SEQ ID NO: 201. In certain embodiments, the targeting sequence is SEQ ID NO: 202. In certain embodiments, the targeting sequence is SEQ ID NO: 203. In certain embodiments, the targeting sequence is SEQ ID NO: 204. In certain embodiments, the targeting sequence is SEQ ID NO: 205. In certain embodiments, the targeting sequence is SEQ ID NO: 206. In certain embodiments, the targeting sequence is SEQ ID NO: 207. In certain embodiments, the targeting sequence is SEQ ID NO: 208. In certain embodiments, the targeting sequence is SEQ ID NO: 209. In certain embodiments, the targeting sequence is SEQ ID NO: 210. In certain embodiments, the targeting sequence is SEQ ID NO: 211. In certain embodiments, the targeting sequence is SEQ ID NO: 212. In certain embodiments, the targeting sequence is SEQ ID NO: 213. In certain embodiments, the targeting sequence is SEQ ID NO: 214. In certain embodiments, the targeting sequence is SEQ ID NO: 215. In certain embodiments, the targeting sequence is SEQ ID NO: 216. In certain embodiments, the targeting sequence is SEQ ID NO: 217. In certain embodiments, the targeting sequence is SEQ ID NO: 218. In certain embodiments, the targeting sequence is SEQ ID NO: 219. In certain embodiments, the targeting sequence is SEQ ID NO: 220. In certain embodiments, the targeting sequence is SEQ ID NO: 221. In certain embodiments, the targeting sequence is SEQ ID NO: 222. In certain embodiments, the targeting sequence is SEQ ID NO: 223. In certain embodiments, the targeting sequence is SEQ ID NO: 224. In certain embodiments, the targeting sequence is SEQ ID NO: 225. In certain embodiments, the targeting sequence is SEQ ID NO: 226. In certain embodiments, the targeting sequence is SEQ ID NO: 227. In certain embodiments, the targeting sequence is SEQ ID NO: 228. In certain embodiments, the targeting sequence is SEQ ID NO: 229. In certain embodiments, the targeting sequence is SEQ ID NO: 230. In certain embodiments, the targeting sequence is SEQ ID NO: 231. In certain embodiments, the targeting sequence is SEQ ID NO: 232. In certain embodiments, the targeting sequence is SEQ ID NO: 233. In certain embodiments, the targeting sequence is SEQ ID NO: 234. In certain embodiments, the targeting sequence is SEQ ID NO: 235. In certain embodiments, the targeting sequence is SEQ ID NO: 236. In certain embodiments, the targeting sequence is SEQ ID NO: 237. In certain embodiments, the targeting sequence is SEQ ID NO: 238. In certain embodiments, the targeting sequence is SEQ ID NO: 239. In certain embodiments, the targeting sequence is SEQ ID NO: 240. In certain embodiments, the targeting sequence is SEQ ID NO: 241. In certain embodiments, the targeting sequence is SEQ ID NO: 242. In certain embodiments, the targeting sequence is SEQ ID NO: 243. In certain embodiments, the targeting sequence is SEQ ID NO: 244. In certain embodiments, the targeting sequence is SEQ ID NO: 245. In certain embodiments, the targeting sequence is SEQ ID NO:246. In certain embodiments, the targeting sequence is SEQ ID NO: 247. In certain embodiments, the targeting sequence is SEQ ID NO: 248. In certain embodiments, the targeting sequence is SEQ ID NO: 249. In certain embodiments, the targeting sequence is SEQ ID NO: 250. In certain embodiments, the targeting sequence is SEQ ID NO: 251. In certain embodiments, the targeting sequence is SEQ ID NO: 252. In certain embodiments, the targeting sequence is SEQ ID NO: 253. In certain embodiments, the targeting sequence is SEQ ID NO: 254. In certain embodiments, the targeting sequence is SEQ ID NO: 255. In certain embodiments, the targeting sequence is SEQ ID NO: 256. In certain embodiments, the targeting sequence is SEQ ID NO: 257. In certain embodiments, the targeting sequence is SEQ ID NO: 258. In certain embodiments, the targeting sequence is SEQ ID NO: 259. In certain embodiments, the targeting sequence is SEQ ID NO: 260. In certain embodiments, the targeting sequence is SEQ ID NO: 261. In certain embodiments, the targeting sequence is SEQ ID NO: 262. In certain embodiments, the targeting sequence is SEQ ID NO: 263. In certain embodiments, the targeting sequence is SEQ ID NO: 264. In certain embodiments, the targeting sequence is SEQ ID NO: 265. In certain embodiments, the targeting sequence is SEQ ID NO: 266. In certain embodiments, the targeting sequence is SEQ ID NO: 267. In certain embodiments, the targeting sequence is SEQ ID NO: 268. In certain embodiments, the targeting sequence is SEQ ID NO: 269. In certain embodiments, the targeting sequence is SEQ ID NO: 270. In certain embodiments, the targeting sequence is SEQ ID NO: 271. In certain embodiments, the targeting sequence is SEQ ID NO: 272. In certain embodiments, the targeting sequence is SEQ ID NO: 273. In certain embodiments, the targeting sequence is SEQ ID NO: 274. In certain embodiments, the targeting sequence is SEQ ID NO: 275. In certain embodiments, the targeting sequence is SEQ ID NO: 276. In certain embodiments, the targeting sequence is SEQ ID NO: 277. In certain embodiments, the targeting sequence is SEQ ID NO: 278. In certain embodiments, the targeting sequence is SEQ ID NO: 279. In certain embodiments, the targeting sequence is SEQ ID NO: 280. In certain embodiments, the targeting sequence is SEQ ID NO: 281. In certain embodiments, the targeting sequence is SEQ ID NO: 282. In certain embodiments, the targeting sequence is SEQ ID NO: 283. In certain embodiments, the targeting sequence is SEQ ID NO: 284. In certain embodiments, the targeting sequence is SEQ ID NO: 285. In certain embodiments, the targeting sequence is SEQ ID NO: 286. In certain embodiments, the targeting sequence is SEQ ID NO: 287. In certain embodiments, the targeting sequence is SEQ ID NO: 288. In certain embodiments, the targeting sequence is SEQ ID NO: 289. In certain embodiments, the targeting sequence is SEQ ID NO: 290. In certain embodiments, the targeting sequence is SEQ ID NO: 291. In certain embodiments, the targeting sequence is SEQ ID NO: 292. In certain embodiments, the targetingsequence is SEQ ID NO: 293. In certain embodiments, the targeting sequence is SEQ ID NO: 294. In certain embodiments, the targeting sequence is SEQ ID NO: 295. In certain embodiments, the targeting sequence is SEQ ID NO: 296. In certain embodiments, the targeting sequence is SEQ ID NO: 297. In certain embodiments, the targeting sequence is SEQ ID NO: 298. In certain embodiments, the targeting sequence is SEQ ID NO: 299. In certain embodiments, the targeting sequence is SEQ ID NO: 300. In certain embodiments, the targeting sequence is SEQ ID NO: 301. In certain embodiments, the targeting sequence is SEQ ID NO: 302. In certain embodiments, the targeting sequence is SEQ ID NO: 303. In certain embodiments, the targeting sequence is SEQ ID NO: 304. In certain embodiments, the targeting sequence is SEQ ID NO: 305. In certain embodiments, the targeting sequence is SEQ ID NO: 306. In certain embodiments, the targeting sequence is SEQ ID NO: 307. In certain embodiments, the targeting sequence is SEQ ID NO: 308. In certain embodiments, the targeting sequence is SEQ ID NO: 309. In certain embodiments, the targeting sequence is SEQ ID NO: 310. In certain embodiments, the targeting sequence is SEQ ID NO: 311. In certain embodiments, the targeting sequence is SEQ ID NO: 312. In certain embodiments, the targeting sequence is SEQ ID NO: 313. In certain embodiments, the targeting sequence is SEQ ID NO: 314. In certain embodiments, the targeting sequence is SEQ ID NO: 315. In certain embodiments, the targeting sequence is SEQ ID NO: 316. In certain embodiments, the targeting sequence is SEQ ID NO: 317. In certain embodiments, the targeting sequence is SEQ ID NO: 318. In certain embodiments, the targeting sequence is SEQ ID NO: 319. In certain embodiments, the targeting sequence is SEQ ID NO: 320. In certain embodiments, the targeting sequence is SEQ ID NO: 321. In certain embodiments, the targeting sequence is SEQ ID NO: 322. In certain embodiments, the targeting sequence is SEQ ID NO: 323. In certain embodiments, the targeting sequence is SEQ ID NO: 324. In certain embodiments, the targeting sequence is SEQ ID NO: 325. In certain embodiments, the targeting sequence is SEQ ID NO: 326.

[0140] In certain embodiments, the target region is within the exon internal region of exon 2 (SEQ ID NO: 2), the intron 1 / exon 2 junction, the exon 2 / intron 2 junction, or the intron internal region of intron 2 (SEQ ID NO: 11) of the human DNM2 gene pre-mRNA. In certain embodiments, the target region of the human DNM2 gene pre-mRNA is within the 21stnucleotide to the 47thnucleotide of exon 2 measured from the 5′ end of exon 2 (SEQ ID NO: 2). In certain embodiments, the target region is a region within SEQ ID NO: 13. In certain embodiments, the target region is a region within DNM2 H2A(+21+47).

[0141] In certain embodiments, the target region of the human DNM2 gene pre-mRNA is within the 23rdnucleotide to the 51stnucleotide of exon 2 measured from the 5′ end of exon 2 (SEQ IDNO: 2). In certain embodiments, the target region is a region within SEQ ID NO: 14. In certain embodiments, the target region is a region within DNM2 H2A(+23+51).

[0142] In certain embodiments, the target region of the human DNM2 gene pre-mRNA is within the 46thnucleotide to the 72ndnucleotide of exon 2 measured from the 5′ end of exon 2 (SEQ ID NO: 2). In certain embodiments, the target region is a region within SEQ ID NO: 15. In certain embodiments, the target region is a region within DNM2 H2A(+46+72).

[0143] In certain embodiments, the target region of the human DNM2 gene pre-mRNA is within the 13thnucleotide of exon 2 measured from the 3′ end of exon 2 (SEQ ID NO: 2) to the 24thnucleotide of intron 2 measured from the 3′ end of exon 2. In certain embodiments, the target region is a region within SEQ ID NO: 16. In certain embodiments, the target region is a region within DNM2 H2D(+13-24).

[0144] In certain embodiments, the target region of the human DNM2 gene pre-mRNA is within the 13thnucleotide of exon 2 measured from the 3′ end of exon 2 (SEQ ID NO: 2) to the 14thnucleotide of intron 2 measured from the 3′ end of exon 2. In certain embodiments, the target region is a region within SEQ ID NO: 17. In certain embodiments, the target region is a region within DNM2 H2D(+13-14).

[0145] In certain embodiments, the target region of the human DNM2 gene pre-mRNA is within the 10thnucleotide of exon 2 measured from the 3′ end of exon 2 (SEQ ID NO: 2) to the 19thnucleotide of intron 2 measured from the 3′ end of exon 2. In certain embodiments, the target region is a region within SEQ ID NO: 18. In certain embodiments, the target region is a region within DNM2 H2D(+10-19).

[0146] In certain embodiments, the target region of the human DNM2 gene pre-mRNA is within the 9thnucleotide of exon 2 measured from the 3′ end of exon 2 (SEQ ID NO: 2) to the 18thnucleotide of intron 2 measured from the 3′ end of exon 2. In certain embodiments, the target region is a region within SEQ ID NO: 19. In certain embodiments, the target region is a region within DNM2 H2D(+9-18).

[0147] In certain embodiments, the target region of the human DNM2 gene pre-mRNA is within the 6thnucleotide of exon 2 measured from the 3′ end of exon 2 (SEQ ID NO: 2) to the 23rdnucleotide of intron 2 measured from the 3′ end of exon 2. In certain embodiments, the target region is a region within SEQ ID NO: 20. In certain embodiments, the target region is a region within DNM2 H2D(+6-23).

[0148] In certain embodiments, the target region of the human DNM2 gene pre-mRNA is within the 4thnucleotide of exon 2 measured from the 3′ end of exon 2 (SEQ ID NO: 2) to the 23rdnucleotide of intron 2 measured from the 3′ end of exon 2. In certain embodiments, the targetregion is a region within SEQ ID NO: 21. In certain embodiments, the target region is a region within DNM2 H2D(+4-23).

[0149] In certain embodiments, the target region of the human DNM2 gene pre-mRNA is within the 1stnucleotide to the 30thnucleotide of intron 2 (SEQ ID NO: 11) measured from the 3′ end of exon 2 (SEQ ID NO: 2). In certain embodiments, the target region is a region within SEQ ID NO: 22. In certain embodiments, the target region is a region within DNM2 H2D(-1-30).

[0150] In certain embodiments, the target region of the human DNM2 gene pre-mRNA is within the 1stnucleotide to the 29thnucleotide of intron 2 (SEQ ID NO: 11) measured from the 3′ end of exon 2 (SEQ ID NO: 2). In certain embodiments, the target region is a region within SEQ ID NO: 23. In certain embodiments, the target region is a region within DNM2 H2D(-1-29).

[0151] In certain embodiments, the target region of the human DNM2 gene pre-mRNA is DNM2 H2A (-10+15), DNM2 H2A(-7+17), DNM2 H2A(+3+27), DNM2 H2A(+15+37), DNM2 H2A(+21+45), DNM2 H2A(+23+47), DNM2 H2A(+27+51), DNM2 H2A(+37+61), DNM2 H2A(+46+70), DNM2 H2A (+48+72), DNM2 H2D(+20-5), DNM2 H2D (+13-12), DNM2 H2D(+12- 13), DNM2 H2D(+11-14), DNM2 H2D(+10-15), DNM2 H2D(+9-16), DNM2 H2D(+8-17), DNM2 H2D(+7-18), DNM2 H2D(+6-19), DNM2 H2D(+5-20), DNM2 H2D(+4-21), DNM2 H2D(+3-22), DNM2 H2D(+2-23), DNM2 H2D(+1-24), DNM2 H2D(-1-25), DNM2 H2D(-2-26), DNM2 H2D(-3- 27), DNM2 H2D(-4-28), DNM2 H2D(-5-29), or DNM2 H2D(-6-30).

[0152] In certain embodiments, the target region of the human DNM2 gene pre-mRNA is DNM2 H2D (+13-12), DNM2 H2D(+12-13), DNM2 H2D(+11-14), DNM2 H2D(+10-15), DNM2 H2D(+9- 16), DNM2 H2D(+8-17), DNM2 H2D(+7-18), DNM2 H2D(+6-19), DNM2 H2D(+5-20), DNM2 H2D(+4-21), DNM2 H2D(+3-22), DNM2 H2D(+2-23) , DNM2 H2D(+1-24), DNM2 H2D(-1-25), DNM2 H2D(-2-26), DNM2 H2D(-3-27), DNM2 H2D(-4-28), DNM2 H2D(-5-29), or DNM2 H2D(-6- 30).

[0153] In certain embodiments, the target region is DNM2 H2A(+21+45) or DNM2 H2A(+23+47). In certain embodiments, the target region is DNM2 H2A(+23+47) or DNM2 H2A(+27+51). In certain embodiments, the target region is DNM2 H2A(+46+70) or DNM2 H2A(+48+72).

[0154] In certain embodiments, the target region is DNM2 H2D(+13-12), DNM2 H2D(+12-13), DNM2 H2D(+11-14), DNM2 H2D(+10-15), DNM2 H2D(+9-16), DNM2 H2D(+8-17), DNM2 H2D(+7-18), DNM2 H2D(+6-19), DNM2 H2D(+5-20), DNM2 H2D(+4-21), DNM2 H2D(+3-22), DNM2 H2D(+2-23), or DNM2 H2D(+1-24). In certain embodiments, the target region is DNM2 H2D (+13-12), DNM2 H2D(+12-13), or DNM2 H2D(+11-14).

[0155] In certain embodiments, the target region is DNM2 H2D(+10-15), DNM2 H2D(+9-16), DNM2 H2D(+8-17), DNM2 H2D(+7-18), or DNM2 H2D(+6-19). In certain embodiments, thetarget region is DNM2 H2D(+9-16), DNM2 H2D(+8-17), or DNM2 H2D(+7-18). In certain embodiments, the target region is DNM2 H2D(+8-17).

[0156] In certain embodiments, the target region is DNM2 H2D(+6-19), DNM2 H2D(+5-20), DNM2 H2D(+4-21), DNM2 H2D(+3-22), DNM2 H2D(+2-23). In certain embodiments, the target region is DNM2 H2D(+4-21), DNM2 H2D(+3-22), or DNM2 H2D(+2-23). In certain embodiments, the target region is DNM2 H2D(+3-22).

[0157] In certain embodiments, the target region is DNM2 H2D(-1-25), DNM2 H2D(-2-26), DNM2 H2D(-3-27), DNM2 H2D(-4-28), DNM2 H2D(-5-29), or DNM2 H2D(-6-30). In certain embodiments, the target region is DNM2 H2D(-1-25), DNM2 H2D(-2-26), DNM2 H2D(-3-27), DNM2 H2D(-4-28), or DNM2 H2D(-5-29).

[0158] In certain embodiments, the target region of the human DNM2 gene pre-mRNA is DNM2 H2A (-10+15). In certain embodiments, the target region of the human DNM2 gene pre-mRNA is DNM2 H2A(-7+17). In certain embodiments, the target region of the human DNM2 gene pre- mRNA is DNM2 H2A(+3+27). In certain embodiments, the target region of the human DNM2 gene pre-mRNA is DNM2 H2A(+15+37). In certain embodiments, the target region of the human DNM2 gene pre-mRNA is DNM2 H2A(+37+61). In certain embodiments, the target region of the human DNM2 gene pre-mRNA is DNM2 H2D(+20-5).

[0159] In certain embodiments, the targeting sequence is selected from: SEQ ID NO: 67 (CGGGGAAGGAAGTCCCTGTGAGGGG); SEQ ID NO: 68 (CGCGGBGAAGGAAGTCCCTGTGAG); SEQ ID NO: 69 (ATTCCTGAACCGCGBGGAAGGAAGT); SEQ ID NO: 70 (CCGGGTGACGATTCCTGAACCGC); SEQ ID NO: 71 (AGAGGCCGCCGGGTGACGATTCCTG); SEQ ID NO: 72 (TGAGAGGCCGCCGGGTGACGATTCC); SEQ ID NO: 73 (AGAATGAGAGGCCGCCGGGTGACGA); SEQ ID NO: 74 (GATGAGCTGCAGAATGAGAGGCCGC); SEQ ID NO: 75 (TTTTGAGAAGATGAGCTGCAGAATG); SEQ ID NO: 76 (GTTTTTGAGAAGATGAGCTGCAGAA); SEQ ID NO: 77 (TTTACCTGTTTTTGAGAAGATGAGC); SEQ ID NO: 78 (GCCCCATTTTACCTGTTTTTGAGAA); SEQ ID NO: 79 (CGCCCCATTTTACCTGTTTTTGAGA); SEQ ID NO: 80 (CCGCCCCATTTTACCTGTTTTTGAG); SEQ ID NO: 81 (GCCGCCCCATTTTACCTGTTTTTGA); SEQ ID NO: 82 (GGCCGCCCCATTTTACCTGTTTTTG); SEQ ID NO: 83 (AGGCCGCCCCATTTTACCTGTTTTT);SEQ ID NO: 84 (CAGGCCGCCCCATTTTACCTGTTTT); SEQ ID NO: 85 (TCAGGCCGCCCCATTTTACCTGTTT); SEQ ID NO: 86 (CTCAGGCCGCCCCATTTTACCTGTT); SEQ ID NO: 87 (CCTCAGGCCGCCCCATTTTACCTGT); SEQ ID NO: 88 (ACCTCAGGCCGCCCCATTTTACCTG); SEQ ID NO: 89 (AACCTCAGGCCGCCCCATTTTACCT); SEQ ID NO: 90 (GAACCTCAGGCCGCCCCATTTTACC); SEQ ID NO: 91 (TGAACCTCAGGCCGCCCCATTTTAC); SEQ ID NO: 92 (CTGAACCTCAGGCCGCCCCATTTTA); SEQ ID NO: 93 (GCTGAACCTCAGGCCGCCCCATTTT); SEQ ID NO: 94 (TGCTGAACCTCAGGCCGCCCCATTT); SEQ ID NO: 95 (CTGCTGAACCTCAGGCCGCCCCATT); and SEQ ID NO: 96 (CCTGCTGAACCTCAGGCCGCCCCAT), wherein “B” represents an abasic subunit or guanine. In certain embodiments, B is an abasic subunit.

[0160] In certain embodiments, the targeting sequence is selected from: SEQ ID NO: 78 (GCCCCATTTTACCTGTTTTTGAGAA); SEQ ID NO: 79 (CGCCCCATTTTACCTGTTTTTGAGA); SEQ ID NO: 80 (CCGCCCCATTTTACCTGTTTTTGAG); SEQ ID NO: 81 (GCCGCCCCATTTTACCTGTTTTTGA); SEQ ID NO: 82 (GGCCGCCCCATTTTACCTGTTTTTG); SEQ ID NO: 83 (AGGCCGCCCCATTTTACCTGTTTTT); SEQ ID NO: 84 (CAGGCCGCCCCATTTTACCTGTTTT); SEQ ID NO: 85 (TCAGGCCGCCCCATTTTACCTGTTT); SEQ ID NO: 86 (CTCAGGCCGCCCCATTTTACCTGTT); SEQ ID NO: 87 (CCTCAGGCCGCCCCATTTTACCTGT); SEQ ID NO: 88 (ACCTCAGGCCGCCCCATTTTACCTG); SEQ ID NO: 89 (AACCTCAGGCCGCCCCATTTTACCT); SEQ ID NO: 90 (GAACCTCAGGCCGCCCCATTTTACC); SEQ ID NO: 91 (TGAACCTCAGGCCGCCCCATTTTAC); SEQ ID NO: 92 (CTGAACCTCAGGCCGCCCCATTTTA); SEQ ID NO: 93 (GCTGAACCTCAGGCCGCCCCATTTT); SEQ ID NO: 94 (TGCTGAACCTCAGGCCGCCCCATTT); SEQ ID NO: 95 (CTGCTGAACCTCAGGCCGCCCCATT); and SEQ ID NO: 96 (CCTGCTGAACCTCAGGCCGCCCCAT).

[0161] In certain embodiments, the targeting sequence is selected from: SEQ ID NO: 71 (AGAGGCCGCCGGGTGACGATTCCTG); and SEQ ID NO: 72 (TGAGAGGCCGCCGGGTGACGATTCC).

[0162] In certain embodiments, the targeting sequence is selected from: SEQ ID NO: 72 (TGAGAGGCCGCCGGGTGACGATTCC); and SEQ ID NO: 73 (AGAATGAGAGGCCGCCGGGTGACGA).

[0163] In certain embodiments, the targeting sequence is selected from: SEQ ID NO: 75 (TTTTGAGAAGATGAGCTGCAGAATG); and SEQ ID NO: 76 (GTTTTTGAGAAGATGAGCTGCAGAA).

[0164] In certain embodiments, the targeting sequence is selected from: SEQ ID NO: 78 (GCCCCATTTTACCTGTTTTTGAGAA); SEQ ID NO: 79 (CGCCCCATTTTACCTGTTTTTGAGA); SEQ ID NO: 80 (CCGCCCCATTTTACCTGTTTTTGAG); SEQ ID NO: 81 (GCCGCCCCATTTTACCTGTTTTTGA); SEQ ID NO: 82 (GGCCGCCCCATTTTACCTGTTTTTG); SEQ ID NO: 83 (AGGCCGCCCCATTTTACCTGTTTTT); SEQ ID NO: 84 (CAGGCCGCCCCATTTTACCTGTTTT); SEQ ID NO: 85 (TCAGGCCGCCCCATTTTACCTGTTT); SEQ ID NO: 86 (CTCAGGCCGCCCCATTTTACCTGTT); SEQ ID NO: 87 (CCTCAGGCCGCCCCATTTTACCTGT); SEQ ID NO: 88 (ACCTCAGGCCGCCCCATTTTACCTG); SEQ ID NO: 89 (AACCTCAGGCCGCCCCATTTTACCT); and SEQ ID NO: 90 (GAACCTCAGGCCGCCCCATTTTACC).

[0165] In certain embodiments, the targeting sequence is selected from: SEQ ID NO: 78 (GCCCCATTTTACCTGTTTTTGAGAA); SEQ ID NO: 79 (CGCCCCATTTTACCTGTTTTTGAGA); and SEQ ID NO: 80 (CCGCCCCATTTTACCTGTTTTTGAG).

[0166] In certain embodiments, the targeting sequence is selected from: SEQ ID NO: 81 (GCCGCCCCATTTTACCTGTTTTTGA); SEQ ID NO: 82 (GGCCGCCCCATTTTACCTGTTTTTG); SEQ ID NO: 83 (AGGCCGCCCCATTTTACCTGTTTTT); SEQ ID NO: 84 (CAGGCCGCCCCATTTTACCTGTTTT); and SEQ ID NO: 85 (TCAGGCCGCCCCATTTTACCTGTTT).

[0167] In certain embodiments, the targeting sequence is selected from: SEQ ID NO: 82 (GGCCGCCCCATTTTACCTGTTTTTG);SEQ ID NO: 83 (AGGCCGCCCCATTTTACCTGTTTTT); and SEQ ID NO: 84 (CAGGCCGCCCCATTTTACCTGTTTT).

[0168] In certain embodiments, the targeting sequence is SEQ ID NO: 83.

[0169] In certain embodiments, the targeting sequence is selected from: SEQ ID NO: 85 (TCAGGCCGCCCCATTTTACCTGTTT); SEQ ID NO: 86 (CTCAGGCCGCCCCATTTTACCTGTT); SEQ ID NO: 87 (CCTCAGGCCGCCCCATTTTACCTGT); SEQ ID NO: 88 (ACCTCAGGCCGCCCCATTTTACCTG); and SEQ ID NO: 89 (AACCTCAGGCCGCCCCATTTTACCT).

[0170] In certain embodiments, the targeting sequence is selected from: SEQ ID NO: 87 (CCTCAGGCCGCCCCATTTTACCTGT); SEQ ID NO: 88 (ACCTCAGGCCGCCCCATTTTACCTG); and SEQ ID NO: 89 (AACCTCAGGCCGCCCCATTTTACCT).

[0171] In certain embodiments, the targeting sequence is SEQ ID NO: 88.

[0172] In certain embodiments, the targeting sequence is selected from: SEQ ID NO: 91 (TGAACCTCAGGCCGCCCCATTTTAC); SEQ ID NO: 92 (CTGAACCTCAGGCCGCCCCATTTTA); SEQ ID NO: 93 (GCTGAACCTCAGGCCGCCCCATTTT); SEQ ID NO: 94 (TGCTGAACCTCAGGCCGCCCCATTT); SEQ ID NO: 95 (CTGCTGAACCTCAGGCCGCCCCATT); and SEQ ID NO: 96 (CCTGCTGAACCTCAGGCCGCCCCAT).

[0173] In certain embodiments, the targeting sequence is selected from: SEQ ID NO: 91 (TGAACCTCAGGCCGCCCCATTTTAC); SEQ ID NO: 92 (CTGAACCTCAGGCCGCCCCATTTTA); SEQ ID NO: 93 (GCTGAACCTCAGGCCGCCCCATTTT); SEQ ID NO: 94 (TGCTGAACCTCAGGCCGCCCCATTT); and SEQ ID NO: 95 (CTGCTGAACCTCAGGCCGCCCCATT).

[0174] In certain embodiments, the targeting sequence is selected from: SEQ ID NO: 67 (CGGGGAAGGAAGTCCCTGTGAGGGG); SEQ ID NO: 68 (CGCGGBGAAGGAAGTCCCTGTGAG); SEQ ID NO: 69 (ATTCCTGAACCGCGBGGAAGGAAGT); SEQ ID NO: 70 (CCGGGTGACGATTCCTGAACCGC); SEQ ID NO: 74 (GATGAGCTGCAGAATGAGAGGCCGC); and SEQ ID NO: 77 (TTTACCTGTTTTTGAGAAGATGAGC), wherein “B” represents an abasic subunit or guanine. In certain embodiments, B is an abasic subunit.

[0175] In certain embodiments, the target region is within the exon internal region of exon 9 (SEQ ID NO: 6), the intron 8 / exon 9 junction, or the exon 9 / intron 9 junction of the human DNM2 gene pre-mRNA.

[0176] In certain embodiments, the target region of the human DNM2 gene pre-mRNA is within the 36thnucleotide to the 61stnucleotide of exon 9 measured from the 5′ end of exon 9 (SEQ ID NO: 6). In certain embodiments, the target region is a region within SEQ ID NO: 24. In certain embodiments, the target region is a region within DNM2 H9A(+36+61).

[0177] In certain embodiments, the target region of the human DNM2 gene pre-mRNA is within the 42ndnucleotide to the 68thnucleotide of exon 9 measured from the 5′ end of exon 9 (SEQ ID NO: 6). In certain embodiments, the target region is a region within SEQ ID NO: 25. In certain embodiments, the target region is a region within DNM2 H9A(+42+70).

[0178] In certain embodiments, the target region of the human DNM2 gene pre-mRNA is within the 43rdnucleotide to the 68thnucleotide of exon 9 measured from the 5′ end of exon 9 (SEQ ID NO: 6). In certain embodiments, the target region is a region within SEQ ID NO: 26. In certain embodiments, the target region is a region within DNM2 H9A(+42+68).

[0179] In certain embodiments, the target region of the human DNM2 gene pre-mRNA is within the 24thnucleotide of exon 9 measured from the 3′ end of exon 9 (SEQ ID NO: 6) to the 15thnucleotide of intron 9 measured from the 3′ end of exon 9. In certain embodiments, the target region is a region within SEQ ID NO: 27. In certain embodiments, the target region is a region within DNM2 H9D(+24-15).

[0180] In certain embodiments, the target region of the human DNM2 gene pre-mRNA is within the 24thnucleotide of exon 9 measured from the 3′ end of exon 9 (SEQ ID NO: 6) to the 5thnucleotide of intron 9 measured from the 3′ end of exon 9. In certain embodiments, the target region is a region within SEQ ID NO: 28. In certain embodiments, the target region is a region within DNM2 H9D(+24-5).

[0181] In certain embodiments, the target region of the human DNM2 gene pre-mRNA is within the 19thnucleotide of exon 9 measured from the 3′ end of exon 9 (SEQ ID NO: 6) to the 10thnucleotide of intron 9 measured from the 3′ end of exon 9. In certain embodiments, the target region is a region within SEQ ID NO: 29. In certain embodiments, the target region is a region within DNM2 H9D(+19-10).

[0182] In certain embodiments, the target region of the human DNM2 gene pre-mRNA is within the 14thnucleotide of exon 9 measured from the 3′ end of exon 9 (SEQ ID NO: 6) to the 15thnucleotide of intron 9 measured from the 3′ end of exon 9. In certain embodiments, the target region is a region within SEQ ID NO: 30. In certain embodiments, the target region is a region within DNM2 H9D(+14-15).

[0183] In certain embodiments, the target region of the human DNM2 gene pre-mRNA is within the 9thnucleotide of exon 9 measured from the 3′ end of exon 9 (SEQ ID NO: 6) to the 22ndnucleotide of intron 9 measured from the 3′ end of exon 9. In certain embodiments, the target region is a region within SEQ ID NO: 31. In certain embodiments, the target region is a region within DNM2 H9D(+9-22).

[0184] In certain embodiments, the target region of the human DNM2 gene pre-mRNA is within the 9thnucleotide of exon 9 measured from the 3′ end of exon 9 (SEQ ID NO: 6) to the 20thnucleotide of intron 9 measured from the 3′ end of exon 9. In certain embodiments, the target region is a region within SEQ ID NO: 32. In certain embodiments, the target region is a region within DNM2 H9D(+9-20).

[0185] In certain embodiments, the target region of the human DNM2 gene pre-mRNA is within the 9thnucleotide of exon 9 measured from the 3′ end of exon 9 (SEQ ID NO: 6) to the 18thnucleotide of intron 9 measured from the 3′ end of exon 9. In certain embodiments, the target region is a region within SEQ ID NO: 33. In certain embodiments, the target region is a region within DNM2 H9D(+9-18).

[0186] In certain embodiments, the target region of the human DNM2 gene pre-mRNA is within the 8thnucleotide of exon 9 measured from the 3′ end of exon 9 (SEQ ID NO: 6) to the 21stnucleotide of intron 9 measured from the 3′ end of exon 9. In certain embodiments, the target region is a region within SEQ ID NO: 34. In certain embodiments, the target region is a region within DNM2 H9D(+8-21).

[0187] In certain embodiments, the target region of the human DNM2 gene pre-mRNA is within the 6thnucleotide of exon 9 measured from the 3′ end of exon 9 (SEQ ID NO: 6) to the 22ndnucleotide of intron 9 measured from the 3′ end of exon 9. In certain embodiments, the target region is a region within SEQ ID NO: 35. In certain embodiments, the target region is a region within DNM2 H9D(+6-22).

[0188] In certain embodiments, the target region of the human DNM2 gene pre-mRNA is DNM2 H9A(-12+13), DNM2 H9A(-5+20), DNM2 H9A(+1+25),DNM2 H9A(+6+30), DNM2 H9A(+16+40), DNM2 H9A(+25+49), DNM2 H9A(+36+60), DNM2 H9A(+37+61), DNM2 H9A(+42+66), DNM2 H9A(+43+62), DNM2 H9A(+43+63), DNM2 H9A(+43+64), DNM2 H9A(+43+65), DNM2 H9A(+43+66), DNM2 H9A(+43+67), DNM2 H9A(+44+67), DNM2 H9A(+44+68), DNM2 H9A(+45+67), DNM2 H9A (+46+67), DNM2 H9A(+47+67), DNM2 H9A(+48+67), DNM2 H9D(+24-1), DNM2 H9D(+23-2), DNM2 H9D(+22-3), DNM2 H9D(+21-4), DNM2 H9D(+20-5), DNM2 H9D(+19-6), DNM2 H9D (+18-7), DNM2 H9D(+17-8), DNM2 H9D(+16-9), DNM2 H9D(+15-10), DNM2 H9D(+14-11), DNM2 H9D(+13-12), DNM2 H9D(+12-13), DNM2 H9D(+11- 14), DNM2 H9D(+10-15), DNM2 H9D(+9-16), DNM2 H9D(+8-12), DNM2 H9D(+8-13), DNM2H9D(+8-14), DNM2 H9D(+8-15), DNM2 H9D(+8-17), DNM2 H9D(+7-18), DNM2 H9D(+7-17), DNM2 H9D(+6-19), DNM2 H9D(+6-17), DNM2 H9D(+5-17), DNM2 H9D(+5-20), DNM2 H9D(+4- 17), DNM2 H9D(+4-21), DNM2 H9D(+3-17), or DNM2 H9D(+3-22).

[0189] In certain embodiments, the target region of the human DNM2 gene pre-mRNA is DNM2 H9A(+16+40), DNM2 H9A(+25+49), DNM2 H9A(+36+60), DNM2 H9A(+37+61), DNM2 H9A(+43+67), DNM2 H9A(+42+66), DNM2 H9A(+44+68), DNM2 H9D(+24-1), DNM2 H9D(+23- 2), DNM2 H9D(+22-3), DNM2 H9D(+21-4), DNM2 H9D(+20-5), DNM2 H9D(+19-6), DNM2 H9D (+18-7), DNM2 H9D(+17-8), DNM2 H9D(+16-9), DNM2 H9D(+15-10), DNM2 H9D(+14-11), DNM2 H9D(+13-12), DNM2 H9D(+12-13), DNM2 H9D(+11-14), DNM2 H9D(+10-15), DNM2 H9D(+9-16), DNM2 H9D(+8-17), DNM2 H9D(+7-18), DNM2 H9D(+6-19), DNM2 H9D(+5-20), DNM2 H9D(+4-21), or DNM2 H9D(+3-22).

[0190] In certain embodiments, the target region of the human DNM2 gene pre-mRNA is DNM2 H9A(+36+60) or DNM2 H9A(+37+61).

[0191] In certain embodiments, the target region of the human DNM2 gene pre-mRNA is DNM2 H9A(+42+66), DNM2 H9A(+43+62), DNM2 H9A(+43+63), DNM2 H9A(+43+64), DNM2 H9A(+43+65), DNM2 H9A(+43+66), DNM2 H9A(+43+67), DNM2 H9A(+44+67), DNM2 H9A(+44+68), DNM2 H9A(+45+67), DNM2 H9A (+46+67), DNM2 H9A(+47+67), or DNM2 H9A(+48+67). In certain embodiments, the target region of the human DNM2 gene pre-mRNA is DNM2 H9A(+43+62), DNM2 H9A(+43+63), DNM2 H9A(+43+64), DNM2 H9A(+43+65), DNM2 H9A(+43+66), DNM2 H9A(+43+67), DNM2 H9A(+44+67), or DNM2 H9A(+44+68). In certain embodiments, the target region of the human DNM2 gene pre-mRNA is DNM2 H9A(+43+67).

[0192] In certain embodiments, the target region of the human DNM2 gene pre-mRNA is DNM2 H9D(+24-1), DNM2 H9D(+23-2), DNM2 H9D(+22-3), DNM2 H9D(+21-4), DNM2 H9D(+20-5), DNM2 H9D(+19-6), DNM2 H9D (+18-7), DNM2 H9D(+17-8), DNM2 H9D(+16-9), DNM2 H9D(+15-10), DNM2 H9D(+14-11), DNM2 H9D(+13-12), DNM2 H9D(+12-13), DNM2 H9D(+11- 14), or DNM2 H9D(+10-15). In certain embodiments, the target region of the human DNM2 gene pre-mRNA is DNM2 H9D(+24-1), DNM2 H9D(+23-2), DNM2 H9D(+22-3), DNM2 H9D(+21-4), or DNM2 H9D(+20-5). In certain embodiments, the target region of the human DNM2 gene pre- mRNA is DNM2 H9D(+19-6), DNM2 H9D (+18-7), DNM2 H9D(+17-8), DNM2 H9D(+16-9), or DNM2 H9D(+15-10).

[0193] In certain embodiments, the target region of the human DNM2 gene pre-mRNA is DNM2 H9D(+14-11), DNM2 H9D(+13-12), DNM2 H9D(+12-13), DNM2 H9D(+11-14), or DNM2 H9D(+10-15).

[0194] In certain embodiments, the target region of the human DNM2 gene pre-mRNA is DNM2 H9D(+9-16), DNM2 H9D(+8-12), DNM2 H9D(+8-13), DNM2 H9D(+8-14), DNM2 H9D(+8-15),DNM2 H9D(+8-17), DNM2 H9D(+7-18), DNM2 H9D(+7-17), DNM2 H9D(+6-19), DNM2 H9D(+6- 17), DNM2 H9D(+5-17), DNM2 H9D(+5-20), DNM2 H9D(+4-17), DNM2 H9D(+4-21), DNM2 H9D(+3-17), or DNM2 H9D(+3-22).

[0195] In certain embodiments, the target region of the human DNM2 gene pre-mRNA is DNM2 H9D(+9-16), DNM2 H9D(+8-12), DNM2 H9D(+8-13), DNM2 H9D(+8-14), DNM2 H9D(+8-15), DNM2 H9D(+8-17), DNM2 H9D(+7-18), DNM2 H9D(+7-17), DNM2 H9D(+6-19), DNM2 H9D(+6- 17), DNM2 H9D(+5-17), or DNM2 H9D(+5-20).

[0196] In certain embodiments, the target region of the human DNM2 gene pre-mRNA is DNM2 H9D(+9-16), DNM2 H9D(+8-12), DNM2 H9D(+8-13), DNM2 H9D(+8-14), DNM2 H9D(+8-15), DNM2 H9D(+8-17), or DNM2 H9D(+7-18).

[0197] In certain embodiments, the target region of the human DNM2 gene pre-mRNA is DNM2 H9D(+8-17), DNM2 H9D(+7-18), DNM2 H9D(+7-17), DNM2 H9D(+6-19), DNM2 H9D(+6-17), DNM2 H9D(+5-17), DNM2 H9D(+5-20), DNM2 H9D(+4-17), or DNM2 H9D(+4-21). In certain embodiments, the target region of the human DNM2 gene pre-mRNA is DNM2 H9D(+8-17).

[0198] In certain embodiments, the target region of the human DNM2 gene pre-mRNA is DNM2 H9D(+6-19), DNM2 H9D(+6-17), DNM2 H9D(+5-17), DNM2 H9D(+5-20), DNM2 H9D(+4-17), DNM2 H9D(+4-21), DNM2 H9D(+3-17), or DNM2 H9D(+3-22).

[0199] In certain embodiments, the target region of the human DNM2 gene pre-mRNA is DNM2 H9A(-12+13). In certain embodiments, the target region of the human DNM2 gene pre-mRNA is DNM2 H9A(-5+20). In certain embodiments, the target region of the human DNM2 gene pre- mRNA is DNM2 H9A(+1+25). In certain embodiments, the target region of the human DNM2 gene pre-mRNA is DNM2 H9A(+6+30). In certain embodiments, the target region of the human DNM2 gene pre-mRNA is DNM2 H9A(+16+40). In certain embodiments, the target region of the human DNM2 gene pre-mRNA is DNM2 H9A(+25+49).

[0200] In certain embodiments, the targeting sequence is selected from: SEQ ID NO: 158 (CGTCAAACTCCATCTGAGAAGAGAC); SEQ ID NO: 159 (TCCTTCTCGTCAAACTCCATCTGAG); SEQ ID NO: 160 (GTAAGTCCTTCTCGTCAAACTCCAT); SEQ ID NO: 161 (CCGTCGTAAGTCCTTCTCGTCAAAC); SEQ ID NO: 162 (AGCTGATCTCCCGTCGTAAGTCCTT); SEQ ID NO: 163 (TAATGGCATAGCTGATCTCCCGTCG); SEQ ID NO: 164 (ATGGATGTTCTTAATGGCATAGCTG); SEQ ID NO: 165 (CATGGATGTTCTTAATGGCATAGCT); SEQ ID NO: 166 (GACTCCATGGATGTTCTTAATGGCA); SEQ ID NO: 167 (CCATGGATGTTCTTAATGGC);SEQ ID NO: 168 (TCCATGGATGTTCTTAATGGC); SEQ ID NO: 169 (CTCCATGGATGTTCTTAATGGC); SEQ ID NO: 170 (ACTCCATGGATGTTCTTAATGGC); SEQ ID NO: 171 (GACTCCATGGATGTTCTTAATGGC); SEQ ID NO: 172 (TGACTCCATGGATGTTCTTAATGGC); SEQ ID NO: 173 (TGACTCCATGGATGTTCTTAATGG); SEQ ID NO: 174 (CTGACTCCATGGATGTTCTTAATGG); SEQ ID NO: 175 (TGACTCCATGGATGTTCTTAATG); SEQ ID NO: 176 (TGACTCCATGGATGTTCTTAAT); SEQ ID NO: 177 (TGACTCCATGGATGTTCTTAA); SEQ ID NO: 178 (TGACTCCATGGATGTTCTTA); SEQ ID NO: 179 (CCTGACTCCATGGATGTTCTTAATG); SEQ ID NO: 180 (GCCTGACTCCATGGATGTTCTTAAT); SEQ ID NO: 181 (TGCCTGACTCCATGGATGTTCTTAA); SEQ ID NO: 182 (TTGCCTGACTCCATGGATGTTCTTA); SEQ ID NO: 183 (CTTGCCTGACTCCATGGATGTTCTT); SEQ ID NO: 184 (ACTTGCCTGACTCCATGGATGTTCT); SEQ ID NO: 185 (AACTTGCCTGACTCCATGGATGTTC); SEQ ID NO: 186 (GAACTTGCCTGACTCCATGGATGTT); SEQ ID NO: 187 (GGAACTTGCCTGACTCCATGGATGT); SEQ ID NO: 188 TGGAACTTGCCTGACTCCATGGATG); SEQ ID NO: 189 (GTGGAACTTGCCTGACTCCATGGAT); SEQ ID NO: 190 (CGTGGAACTTGCCTGACTCCATGGA); SEQ ID NO: 191 TCGTGGAACTTGCCTGACTCCATGG); SEQ ID NO: 192 (CTCGTGGAACTTGCCTGACTCCATG); SEQ ID NO: 193 (CCTCGTGGAACTTGCCTGACTCCAT); SEQ ID NO: 194 (TCCTCGTGGAACTTGCCTGACTCCA); SEQ ID NO: 195 (TCCTCGTGGAACTTGCCTGACTCCA); SEQ ID NO: 196 (TCGTGGAACTTGCCTGACTCC); SEQ ID NO: 197 (CTCGTGGAACTTGCCTGACTCC); SEQ ID NO: 198 (CCTCGTGGAACTTGCCTGACTCC); SEQ ID NO: 199 (CTCCTCGTGGAACTTGCCTGACTCC); SEQ ID NO: 200 (TCTCCTCGTGGAACTTGCCTGACTC); SEQ ID NO: 201 (CTCCTCGTGGAACTTGCCTGACTC); SEQ ID NO: 202 (CTCTCCTCGTGGAACTTGCCTGACT);SEQ ID NO: 203 (CTCCTCGTGGAACTTGCCTGACT); SEQ ID NO: 204 (CTCCTCGTGGAACTTGCCTGAC); SEQ ID NO: 205 (ACTCTCCTCGTGGAACTTGCCTGAC); SEQ ID NO: 206 (CTCCTCGTGGAACTTGCCTGA); SEQ ID NO: 207 (GACTCTCCTCGTGGAACTTGCCTGA); SEQ ID NO: 208 (CTCCTCGTGGAACTTGCCTG); and SEQ ID NO: 209 (TGACTCTCCTCGTGGAACTTGCCTG).

[0201] In certain embodiments, the targeting sequence is selected from: SEQ ID NO: 162 (AGCTGATCTCCCGTCGTAAGTCCTT); SEQ ID NO: 163 (TAATGGCATAGCTGATCTCCCGTCG); SEQ ID NO: 164 (ATGGATGTTCTTAATGGCATAGCTG); SEQ ID NO: 165 (CATGGATGTTCTTAATGGCATAGCT); SEQ ID NO: 166 (GACTCCATGGATGTTCTTAATGGCA); SEQ ID NO: 172 (TGACTCCATGGATGTTCTTAATGGC); SEQ ID NO: 174 (CTGACTCCATGGATGTTCTTAATGG); SEQ ID NO: 179 (CCTGACTCCATGGATGTTCTTAATG); SEQ ID NO: 180 (GCCTGACTCCATGGATGTTCTTAAT); SEQ ID NO: 181 (TGCCTGACTCCATGGATGTTCTTAA); SEQ ID NO: 182 (TTGCCTGACTCCATGGATGTTCTTA); SEQ ID NO: 183 (CTTGCCTGACTCCATGGATGTTCTT); SEQ ID NO: 184 (ACTTGCCTGACTCCATGGATGTTCT); SEQ ID NO: 185 (AACTTGCCTGACTCCATGGATGTTC); SEQ ID NO: 186 (GAACTTGCCTGACTCCATGGATGTT); SEQ ID NO: 187 (GGAACTTGCCTGACTCCATGGATGT); SEQ ID NO: 188 TGGAACTTGCCTGACTCCATGGATG); SEQ ID NO: 189 (GTGGAACTTGCCTGACTCCATGGAT); SEQ ID NO: 190 (CGTGGAACTTGCCTGACTCCATGGA); SEQ ID NO: 191 (TCGTGGAACTTGCCTGACTCCATGG); SEQ ID NO: 192 (CTCGTGGAACTTGCCTGACTCCATG); SEQ ID NO: 193 (CCTCGTGGAACTTGCCTGACTCCAT); SEQ ID NO: 194 (TCCTCGTGGAACTTGCCTGACTCCA); SEQ ID NO: 199 (CTCCTCGTGGAACTTGCCTGACTCC); SEQ ID NO: 200 (TCTCCTCGTGGAACTTGCCTGACTC); SEQ ID NO: 205 (ACTCTCCTCGTGGAACTTGCCTGAC); SEQ ID NO: 207 (GACTCTCCTCGTGGAACTTGCCTGA); andSEQ ID NO: 209 (TGACTCTCCTCGTGGAACTTGCCTG).

[0202] In certain embodiments, the targeting sequence is selected from: SEQ ID NO: 164 (ATGGATGTTCTTAATGGCATAGCTG); and SEQ ID NO: 165 (CATGGATGTTCTTAATGGCATAGCT).

[0203] In certain embodiments, the targeting sequence is selected from: SEQ ID NO: 166 (GACTCCATGGATGTTCTTAATGGCA); SEQ ID NO: 167 (CCATGGATGTTCTTAATGGC); SEQ ID NO: 168 TCCATGGATGTTCTTAATGGC); SEQ ID NO: 169 (CTCCATGGATGTTCTTAATGGC); SEQ ID NO: 170 (ACTCCATGGATGTTCTTAATGGC); SEQ ID NO: 171 (GACTCCATGGATGTTCTTAATGGC); SEQ ID NO: 172 (TGACTCCATGGATGTTCTTAATGGC); SEQ ID NO: 173 (TGACTCCATGGATGTTCTTAATGG); SEQ ID NO: 174 (CTGACTCCATGGATGTTCTTAATGG); SEQ ID NO: 175 (TGACTCCATGGATGTTCTTAATG); SEQ ID NO: 176 (TGACTCCATGGATGTTCTTAAT); SEQ ID NO: 177 (TGACTCCATGGATGTTCTTAA); and SEQ ID NO: 178 (TGACTCCATGGATGTTCTTA).

[0204] In certain embodiments, the targeting sequence is selected from: SEQ ID NO: 167 (CCATGGATGTTCTTAATGGC); SEQ ID NO: 168 TCCATGGATGTTCTTAATGGC); SEQ ID NO: 169 (CTCCATGGATGTTCTTAATGGC); SEQ ID NO: 170 (ACTCCATGGATGTTCTTAATGGC); SEQ ID NO: 171 (GACTCCATGGATGTTCTTAATGGC); SEQ ID NO: 172 (TGACTCCATGGATGTTCTTAATGGC); SEQ ID NO: 173 (TGACTCCATGGATGTTCTTAATGG); and SEQ ID NO: 174 (CTGACTCCATGGATGTTCTTAATGG).

[0205] In certain embodiments, the targeting sequence is SEQ ID NO: 172.

[0206] In certain embodiments, the targeting sequence is selected from: SEQ ID NO: 179 (CCTGACTCCATGGATGTTCTTAATG); SEQ ID NO: 180 (GCCTGACTCCATGGATGTTCTTAAT); SEQ ID NO: 181 (TGCCTGACTCCATGGATGTTCTTAA); SEQ ID NO: 182 (TTGCCTGACTCCATGGATGTTCTTA); SEQ ID NO: 183 (CTTGCCTGACTCCATGGATGTTCTT); SEQ ID NO: 184 (ACTTGCCTGACTCCATGGATGTTCT);SEQ ID NO: 185 (AACTTGCCTGACTCCATGGATGTTC); SEQ ID NO: 186 (GAACTTGCCTGACTCCATGGATGTT); SEQ ID NO: 187 (GGAACTTGCCTGACTCCATGGATGT); SEQ ID NO: 188 TGGAACTTGCCTGACTCCATGGATG); SEQ ID NO: 189 (GTGGAACTTGCCTGACTCCATGGAT); SEQ ID NO: 190 (CGTGGAACTTGCCTGACTCCATGGA); SEQ ID NO: 191 TCGTGGAACTTGCCTGACTCCATGG); SEQ ID NO: 192 (CTCGTGGAACTTGCCTGACTCCATG); and SEQ ID NO: 193 (CCTCGTGGAACTTGCCTGACTCCAT).

[0207] In certain embodiments, the targeting sequence is selected from: SEQ ID NO: 179 (CCTGACTCCATGGATGTTCTTAATG); SEQ ID NO: 180 (GCCTGACTCCATGGATGTTCTTAAT); SEQ ID NO: 181 (TGCCTGACTCCATGGATGTTCTTAA); SEQ ID NO: 182 (TTGCCTGACTCCATGGATGTTCTTA); and SEQ ID NO: 183 (CTTGCCTGACTCCATGGATGTTCTT).

[0208] In certain embodiments, the targeting sequence is selected from: SEQ ID NO: 184 (ACTTGCCTGACTCCATGGATGTTCT); SEQ ID NO: 185 (AACTTGCCTGACTCCATGGATGTTC); SEQ ID NO: 186 (GAACTTGCCTGACTCCATGGATGTT); SEQ ID NO: 187 (GGAACTTGCCTGACTCCATGGATGT); and SEQ ID NO: 188 TGGAACTTGCCTGACTCCATGGATG).

[0209] In certain embodiments, the targeting sequence is selected from: SEQ ID NO: 189 (GTGGAACTTGCCTGACTCCATGGAT); SEQ ID NO: 190 (CGTGGAACTTGCCTGACTCCATGGA); SEQ ID NO: 191 (TCGTGGAACTTGCCTGACTCCATGG); SEQ ID NO: 192 (CTCGTGGAACTTGCCTGACTCCATG); and SEQ ID NO: 193 (CCTCGTGGAACTTGCCTGACTCCAT).

[0210] In certain embodiments, the targeting sequence is selected from: SEQ ID NO: 194 (TCCTCGTGGAACTTGCCTGACTCCA); SEQ ID NO: 195 (TCCTCGTGGAACTTGCCTGACTCCA); SEQ ID NO: 196 (TCGTGGAACTTGCCTGACTCC); SEQ ID NO: 197 (CTCGTGGAACTTGCCTGACTCC); SEQ ID NO: 198 (CCTCGTGGAACTTGCCTGACTCC); SEQ ID NO: 199 (CTCCTCGTGGAACTTGCCTGACTCC); SEQ ID NO: 200 (TCTCCTCGTGGAACTTGCCTGACTC);SEQ ID NO: 201 (CTCCTCGTGGAACTTGCCTGACTC); SEQ ID NO: 202 (CTCTCCTCGTGGAACTTGCCTGACT); SEQ ID NO: 203 (CTCCTCGTGGAACTTGCCTGACT); SEQ ID NO: 204 (CTCCTCGTGGAACTTGCCTGAC); SEQ ID NO: 205 (ACTCTCCTCGTGGAACTTGCCTGAC); SEQ ID NO: 206 (CTCCTCGTGGAACTTGCCTGA); SEQ ID NO: 207 (GACTCTCCTCGTGGAACTTGCCTGA); SEQ ID NO: 208 (CTCCTCGTGGAACTTGCCTG); and SEQ ID NO: 209 (TGACTCTCCTCGTGGAACTTGCCTG).

[0211] In certain embodiments, the targeting sequence is selected from: SEQ ID NO: 194 (TCCTCGTGGAACTTGCCTGACTCCA); SEQ ID NO: 195 (TCCTCGTGGAACTTGCCTGACTCCA); SEQ ID NO: 196 (TCGTGGAACTTGCCTGACTCC); SEQ ID NO: 197 (CTCGTGGAACTTGCCTGACTCC); SEQ ID NO: 198 (CCTCGTGGAACTTGCCTGACTCC); SEQ ID NO: 199 (CTCCTCGTGGAACTTGCCTGACTCC); SEQ ID NO: 200 (TCTCCTCGTGGAACTTGCCTGACTC); SEQ ID NO: 201 (CTCCTCGTGGAACTTGCCTGACTC); SEQ ID NO: 202 (CTCTCCTCGTGGAACTTGCCTGACT); SEQ ID NO: 203 (CTCCTCGTGGAACTTGCCTGACT); SEQ ID NO: 204 (CTCCTCGTGGAACTTGCCTGAC); and SEQ ID NO: 205 (ACTCTCCTCGTGGAACTTGCCTGAC).

[0212] In certain embodiments, the targeting sequence is selected from: SEQ ID NO: 194 (TCCTCGTGGAACTTGCCTGACTCCA); SEQ ID NO: 195 (TCCTCGTGGAACTTGCCTGACTCCA); SEQ ID NO: 196 (TCGTGGAACTTGCCTGACTCC); SEQ ID NO: 197 (CTCGTGGAACTTGCCTGACTCC); SEQ ID NO: 198 (CCTCGTGGAACTTGCCTGACTCC); SEQ ID NO: 199 (CTCCTCGTGGAACTTGCCTGACTCC); and SEQ ID NO: 200 (TCTCCTCGTGGAACTTGCCTGACTC).

[0213] In certain embodiments, the targeting sequence is selected from: SEQ ID NO: 199 (CTCCTCGTGGAACTTGCCTGACTCC); SEQ ID NO: 200 (TCTCCTCGTGGAACTTGCCTGACTC); SEQ ID NO: 201 (CTCCTCGTGGAACTTGCCTGACTC); SEQ ID NO: 202 (CTCTCCTCGTGGAACTTGCCTGACT);SEQ ID NO: 203 (CTCCTCGTGGAACTTGCCTGACT); SEQ ID NO: 204 (CTCCTCGTGGAACTTGCCTGAC); SEQ ID NO: 205 (ACTCTCCTCGTGGAACTTGCCTGAC); SEQ ID NO: 206 (CTCCTCGTGGAACTTGCCTGA); and SEQ ID NO: 207 (GACTCTCCTCGTGGAACTTGCCTGA).

[0214] In certain embodiments, the targeting sequence is SEQ ID NO: 199.

[0215] In certain embodiments, the targeting sequence is selected from: SEQ ID NO: 202 (CTCTCCTCGTGGAACTTGCCTGACT); SEQ ID NO: 203 (CTCCTCGTGGAACTTGCCTGACT); SEQ ID NO: 204 (CTCCTCGTGGAACTTGCCTGAC); SEQ ID NO: 205 (ACTCTCCTCGTGGAACTTGCCTGAC); SEQ ID NO: 206 (CTCCTCGTGGAACTTGCCTGA); SEQ ID NO: 207 (GACTCTCCTCGTGGAACTTGCCTGA); SEQ ID NO: 208 (CTCCTCGTGGAACTTGCCTG); and SEQ ID NO: 209 (TGACTCTCCTCGTGGAACTTGCCTG).

[0216] In certain embodiments, the targeting sequence is selected from: SEQ ID NO: 158 (CGTCAAACTCCATCTGAGAAGAGAC); SEQ ID NO: 159 (TCCTTCTCGTCAAACTCCATCTGAG); SEQ ID NO: 160 (GTAAGTCCTTCTCGTCAAACTCCAT); SEQ ID NO: 161 (CCGTCGTAAGTCCTTCTCGTCAAAC); SEQ ID NO: 162 (AGCTGATCTCCCGTCGTAAGTCCTT); and SEQ ID NO: 163 (TAATGGCATAGCTGATCTCCCGTCG).

[0217] In certain embodiments, the target region is within the exon internal region of exon 12 (SEQ ID NO: 7), the intron 11 / exon 12 junction, or the exon 12 / intron 12 junction of the human DNM2 gene pre-mRNA.

[0218] In certain embodiments, the target region of the human DNM2 gene pre-mRNA is within the 4thnucleotide to the 31stnucleotide measured of exon 12 from the 5′ end of exon 12 (SEQ ID NO: 7). In certain embodiments, the target region is a region within SEQ ID NO: 36. In certain embodiments, the target region is a region within DNM2 H12A(+4+31).

[0219] In certain embodiments, the target region of the human DNM2 gene pre-mRNA is within the 10thnucleotide to the 44thnucleotide of exon 12 measured from the 5′ end of exon 12 (SEQ ID NO: 7). In certain embodiments, the target region is a region within SEQ ID NO: 37. In certain embodiments, the target region is a region within DNM2 H12A(+10+44).

[0220] In certain embodiments, the target region of the human DNM2 gene pre-mRNA is within the 10thnucleotide to the 38thnucleotide of exon 12 measured from the 5′ end of exon 12 (SEQID NO: 7). In certain embodiments, the target region is a region within SEQ ID NO: 38. In certain embodiments, the target region is a region within DNM2 H12A(+10+38).

[0221] In certain embodiments, the target region of the human DNM2 gene pre-mRNA is within the 16thnucleotide to the 44thnucleotide of exon 12 measured from the 5′ end of exon 12 (SEQ ID NO: 7). In certain embodiments, the target region is a region within SEQ ID NO: 39. In certain embodiments, the target region is a region within DNM2 H12A(+16+44).

[0222] In certain embodiments, the target region of the human DNM2 gene pre-mRNA is within the 14thnucleotide to the 42ndnucleotide of exon 12 measured from the 5′ end of exon 12 (SEQ ID NO: 7). In certain embodiments, the target region is a region within SEQ ID NO: 40. In certain embodiments, the target region is a region within DNM2 H12A(+14+42).

[0223] In certain embodiments, the target region of the human DNM2 gene pre-mRNA is within the 25thnucleotide to the 54thnucleotide of exon 12 measured from the 5′ end of exon 12 (SEQ ID NO: 7). In certain embodiments, the target region is a region within SEQ ID NO: 41. In certain embodiments, the target region is a region within DNM2 H12A(+25+54).

[0224] In certain embodiments, the target region of the human DNM2 gene pre-mRNA is within the 25thnucleotide to the 53rdnucleotide of exon 12 measured from the 5′ end of exon 12 (SEQ ID NO: 7). In certain embodiments, the target region is a region within SEQ ID NO: 42. In certain embodiments, the target region is a region within DNM2 H12A(+25+53).

[0225] In certain embodiments, the target region of the human DNM2 gene pre-mRNA is within the 26thnucleotide to the 54thnucleotide of exon 12 measured from the 5′ end of exon 12 (SEQ ID NO: 7). In certain embodiments, the target region is a region within SEQ ID NO: 43. In certain embodiments, the target region is a region within DNM2 H12A(+26+54).

[0226] In certain embodiments, the target region of the human DNM2 gene pre-mRNA is within the 36thnucleotide to the 61stnucleotide of exon 12 measured from the 5′ end of exon 12 (SEQ ID NO: 7). In certain embodiments, the target region is a region within SEQ ID NO: 44. In certain embodiments, the target region is a region within DNM2 H12A(+36+61).

[0227] In certain embodiments, the target region of the human DNM2 gene pre-mRNA is within the 22nd nucleotide of exon 12 measured from the 3′ end of exon 12 (SEQ ID NO: 7) to the 5th nucleotide of intron 12 measured from the 3′ end of exon 12. In certain embodiments, the target region is a region within SEQ ID NO: 45. In certain embodiments, the target region is a region within DNM2 H12D(+22-5).

[0228] In certain embodiments, the target region of the human DNM2 gene pre-mRNA is DNM2 H12A(-13+12), DNM2 H12A(-3+22), DNM2 H12A(+4+28), DNM2 H12A(+7+31), DNM2 H12A(+10+34), DNM2 H12A(+11+35), DNM2 H12A(+12+36), DNM2 H12A(+13+37), DNM2 H12A(+14+38), DNM2 H12A(+15+39), DNM2 H12A(+16+40), DNM2 H12A(+17+41), DNM2H12A(+18+42), DNM2 H12A(+19+43), DNM2 H12A(+20+44), DNM2 H12A(+25+44), DNM2 H12A(+25+45), DNM2 H12A(+25+46), DNM2 H12A(+25+47), DNM2 H12A(+25+48), DNM2 H12A(+25+49), DNM2 H12A(+26+49), DNM2 H12A(+27+49), DNM2 H12A(+28+49), DNM2 H12A(+29+49), DNM2 H12A(+29+53), DNM2 H12A(+30+49), DNM2 H12A(+30+54), DNM2 H12A(+36+60), DNM2 H12A(+37+61), DNM2 H12A(+43+67), DNM2 H12D(+22-3), DNM2 H12D(+20-5), or DNM2 H12D(+15-10).

[0229] In certain embodiments, the target region of the human DNM2 gene pre-mRNA is DNM2 H12A(-3+22), DNM2 H12A(+4+28), DNM2 H12A(+7+31), DNM2 H12A(+10+34), DNM2 H12A(+11+35), DNM2 H12A(+12+36), DNM2 H12A(+13+37), DNM2 H12A(+14+38), DNM2 H12A(+15+39), DNM2 H12A(+16+40), DNM2 H12A(+17+41), DNM2 H12A(+18+42), DNM2 H12A(+19+43), DNM2 H12A(+20+44), DNM2 H12A(+25+49), DNM2 H12A(+29+53), DNM2 H12A(+30+54), DNM2 H12A(+36+60), DNM2 H12A(+37+61), DNM2 H12A(+43+67), DNM2 H12D(+22-3), DNM2 H12D(+20-5), or DNM2 H12D(+15-10).

[0230] In certain embodiments, the target region is DNM2 H12A(+4+28) or DNM2 H12A(+7+31).

[0231] In certain embodiments, the target region is DNM2 H12A(+10+34), DNM2 H12A(+11+35), DNM2 H12A(+12+36), DNM2 H12A(+13+37), DNM2 H12A(+14+38), DNM2 H12A(+15+39), DNM2 H12A(+16+40), DNM2 H12A(+17+41), DNM2 H12A(+18+42), DNM2 H12A(+19+43), DNM2 H12A(+20+44).

[0232] In certain embodiments, the target region is DNM2 H12A(+10+34), DNM2 H12A(+11+35), DNM2 H12A(+12+36), DNM2 H12A(+13+37), or DNM2 H12A(+14+38).

[0233] In certain embodiments, the target region is DNM2 H12A(+16+40), DNM2 H12A(+17+41), DNM2 H12A(+18+42), DNM2 H12A(+19+43), or DNM2 H12A(+20+44).

[0234] In certain embodiments, the target region is DNM2 H12A(+14+38), DNM2 H12A(+15+39), DNM2 H12A(+16+40), DNM2 H12A(+17+41), or DNM2 H12A(+18+42).

[0235] In certain embodiments, the target region is DNM2 H12A(+25+44), DNM2 H12A(+25+45), DNM2 H12A(+25+46), DNM2 H12A(+25+47), DNM2 H12A(+25+48), DNM2 H12A(+25+49), DNM2 H12A(+26+49), DNM2 H12A(+27+49), DNM2 H12A(+28+49), DNM2 H12A(+29+49), DNM2 H12A(+29+53), DNM2 H12A(+30+49), or DNM2 H12A(+30+54).

[0236] In certain embodiments, the target region is DNM2 H12A(+25+44), DNM2 H12A(+25+45), DNM2 H12A(+25+46), DNM2 H12A(+25+47), DNM2 H12A(+25+48), DNM2 H12A(+25+49), DNM2 H12A(+26+49), DNM2 H12A(+27+49), DNM2 H12A(+28+49), DNM2 H12A(+29+49), or DNM2 H12A(+29+53).

[0237] In certain embodiments, the target region is DNM2 H12A(+26+49), DNM2 H12A(+27+49), DNM2 H12A(+28+49), DNM2 H12A(+29+49), DNM2 H12A(+29+53), DNM2H12A(+30+49), or DNM2 H12A(+30+54). In certain embodiments, the target region is DNM2 H12A(+25+49). In certain embodiments, the target region is DNM2 H12A(+36+60) or DNM2 H12A(+37+61).

[0238] In certain embodiments, the target region is DNM2 H12D(+22-3) or DNM2 H12D(+20-5). In certain embodiments, the target region is DNM2 H12A(-13+12). In certain embodiments, the target region is DNM2 H12A(-3+22). In certain embodiments, the target region is DNM2 H12A(+43+67). In certain embodiments, the target region is DNM2 H12D(+15-10).

[0239] In certain embodiments, the targeting sequence is selected from: SEQ ID NO: 210 (CAGCAGAAGAATCTGGBGGAGAGCG); SEQ ID NO: 211 (CAATGTCGATCAGCAGAAGAATCTG); SEQ ID NO: 212 (ACTGCTCAATGTCGATCAGCAGAAG); SEQ ID NO: 213 (AGGACTGCTCAATGTCGATCAGCAG); SEQ ID NO: 214 (TGTAGGACTGCTCAATGTCGATCAG); SEQ ID NO: 215 (ATGTAGGACTGCTCAATGTCGATCA); SEQ ID NO: 216 (GATGTAGGACTGCTCAATGTCGATC); SEQ ID NO: 217 (TGATGTAGGACTGCTCAATGTCGAT); SEQ ID NO: 218 (TTGATGTAGGACTGCTCAATGTCGA); SEQ ID NO: 219 (GTTGATGTAGGACTGCTCAATGTCG); SEQ ID NO: 220 (TGTTGATGTAGGACTGCTCAATGTC); SEQ ID NO: 221 (GTGTTGATGTAGGACTGCTCAATGT); SEQ ID NO: 222 (CGTGTTGATGTAGGACTGCTCAATG); SEQ ID NO: 223 (TCGTGTTGATGTAGGACTGCTCAAT); SEQ ID NO: 224 (TTCGTGTTGATGTAGGACTGCTCAA); SEQ ID NO: 225 (TTCGTGTTGATGTAGGACTG); SEQ ID NO: 226 (GTTCGTGTTGATGTAGGACTG); SEQ ID NO: 227 (GGTTCGTGTTGATGTAGGACTG); SEQ ID NO: 228 (TGGTTCGTGTTGATGTAGGACTG); SEQ ID NO: 229 (ATGGTTCGTGTTGATGTAGGACTG); SEQ ID NO: 230 (CATGGTTCGTGTTGATGTAGGACTG); SEQ ID NO: 231 (CATGGTTCGTGTTGATGTAGGACT); SEQ ID NO: 232 (CATGGTTCGTGTTGATGTAGGAC); SEQ ID NO: 233 (CATGGTTCGTGTTGATGTAGGA); SEQ ID NO: 234 (CATGGTTCGTGTTGATGTAGG); SEQ ID NO: 235 (TCCTCATGGTTCGTGTTGATGTAGG); SEQ ID NO: 236 (CATGGTTCGTGTTGATGTAG);SEQ ID NO: 237 (GTCCTCATGGTTCGTGTTGATGTAG); SEQ ID NO: 238 (GATGAAGTCCTCATGGTTCGTGTTG); SEQ ID NO: 239 (CGATGAAGTCCTCATGGTTCGTGTT); SEQ ID NO: 240 (CAAACCCGATGAAGTCCTCATGGTT); SEQ ID NO: 241 (TACTTGGCAAACCCGATGAAGTCCT); SEQ ID NO: 242 (CCTACTTGGCAAACCCGATGAAGTC); and SEQ ID NO: 243 (AAGTACCTACTTGGCAAACCCGATG).

[0240] In certain embodiments, the targeting sequence is selected from: SEQ ID NO: 211 (CAATGTCGATCAGCAGAAGAATCTG); SEQ ID NO: 212 (ACTGCTCAATGTCGATCAGCAGAAG); SEQ ID NO: 213 (AGGACTGCTCAATGTCGATCAGCAG); SEQ ID NO: 214 (TGTAGGACTGCTCAATGTCGATCAG); SEQ ID NO: 215 (ATGTAGGACTGCTCAATGTCGATCA); SEQ ID NO: 216 (GATGTAGGACTGCTCAATGTCGATC); SEQ ID NO: 217 (TGATGTAGGACTGCTCAATGTCGAT); SEQ ID NO: 218 (TTGATGTAGGACTGCTCAATGTCGA); SEQ ID NO: 219 (GTTGATGTAGGACTGCTCAATGTCG); SEQ ID NO: 220 (TGTTGATGTAGGACTGCTCAATGTC); SEQ ID NO: 221 (GTGTTGATGTAGGACTGCTCAATGT); SEQ ID NO: 222 (CGTGTTGATGTAGGACTGCTCAATG); SEQ ID NO: 223 (TCGTGTTGATGTAGGACTGCTCAAT); SEQ ID NO: 224 (TTCGTGTTGATGTAGGACTGCTCAA); SEQ ID NO: 230 (CATGGTTCGTGTTGATGTAGGACTG); SEQ ID NO: 235 (TCCTCATGGTTCGTGTTGATGTAGG); SEQ ID NO: 236 (CATGGTTCGTGTTGATGTAG); SEQ ID NO: 237 (GTCCTCATGGTTCGTGTTGATGTAG); SEQ ID NO: 238 (GATGAAGTCCTCATGGTTCGTGTTG); SEQ ID NO: 240 (CAAACCCGATGAAGTCCTCATGGTT); SEQ ID NO: 241 (TACTTGGCAAACCCGATGAAGTCCT); SEQ ID NO: 242 (CCTACTTGGCAAACCCGATGAAGTC); and SEQ ID NO: 243 (AAGTACCTACTTGGCAAACCCGATG).

[0241] In certain embodiments, the targeting sequence is selected from: SEQ ID NO: 212 (ACTGCTCAATGTCGATCAGCAGAAG); and SEQ ID NO: 213 (AGGACTGCTCAATGTCGATCAGCAG).

[0242] In certain embodiments, the targeting sequence is selected from: SEQ ID NO: 214 (TGTAGGACTGCTCAATGTCGATCAG); SEQ ID NO: 215 (ATGTAGGACTGCTCAATGTCGATCA); SEQ ID NO: 216 (GATGTAGGACTGCTCAATGTCGATC); SEQ ID NO: 217 (TGATGTAGGACTGCTCAATGTCGAT); SEQ ID NO: 218 (TTGATGTAGGACTGCTCAATGTCGA); SEQ ID NO: 219 (GTTGATGTAGGACTGCTCAATGTCG); SEQ ID NO: 220 (TGTTGATGTAGGACTGCTCAATGTC); SEQ ID NO: 221 (GTGTTGATGTAGGACTGCTCAATGT); SEQ ID NO: 222 (CGTGTTGATGTAGGACTGCTCAATG); SEQ ID NO: 223 (TCGTGTTGATGTAGGACTGCTCAAT); and SEQ ID NO: 224 (TTCGTGTTGATGTAGGACTGCTCAA).

[0243] In certain embodiments, the targeting sequence is selected from: SEQ ID NO: 214 (TGTAGGACTGCTCAATGTCGATCAG); SEQ ID NO: 215 (ATGTAGGACTGCTCAATGTCGATCA); SEQ ID NO: 216 (GATGTAGGACTGCTCAATGTCGATC); SEQ ID NO: 217 (TGATGTAGGACTGCTCAATGTCGAT); and SEQ ID NO: 218 (TTGATGTAGGACTGCTCAATGTCGA).

[0244] In certain embodiments, the targeting sequence is selected from: SEQ ID NO: 220 (TGTTGATGTAGGACTGCTCAATGTC); SEQ ID NO: 221 (GTGTTGATGTAGGACTGCTCAATGT); SEQ ID NO: 222 (CGTGTTGATGTAGGACTGCTCAATG); SEQ ID NO: 223 (TCGTGTTGATGTAGGACTGCTCAAT); and SEQ ID NO: 224 (TTCGTGTTGATGTAGGACTGCTCAA).

[0245] In certain embodiments, the targeting sequence is selected from: SEQ ID NO: 218 (TTGATGTAGGACTGCTCAATGTCGA); SEQ ID NO: 219 (GTTGATGTAGGACTGCTCAATGTCG); SEQ ID NO: 220 (TGTTGATGTAGGACTGCTCAATGTC); SEQ ID NO: 221 (GTGTTGATGTAGGACTGCTCAATGT); and SEQ ID NO: 222 (CGTGTTGATGTAGGACTGCTCAATG).

[0246] In certain embodiments, the targeting sequence is selected from: SEQ ID NO: 225 (TTCGTGTTGATGTAGGACTG); SEQ ID NO: 226 (GTTCGTGTTGATGTAGGACTG); SEQ ID NO: 227 (GGTTCGTGTTGATGTAGGACTG); SEQ ID NO: 228 (TGGTTCGTGTTGATGTAGGACTG);SEQ ID NO: 229 (ATGGTTCGTGTTGATGTAGGACTG); SEQ ID NO: 230 (CATGGTTCGTGTTGATGTAGGACTG); SEQ ID NO: 231 (CATGGTTCGTGTTGATGTAGGACT); SEQ ID NO: 232 (CATGGTTCGTGTTGATGTAGGAC); SEQ ID NO: 233 (CATGGTTCGTGTTGATGTAGGA); SEQ ID NO: 234 (CATGGTTCGTGTTGATGTAGG); SEQ ID NO: 235 (TCCTCATGGTTCGTGTTGATGTAGG); SEQ ID NO: 236 (CATGGTTCGTGTTGATGTAG); and SEQ ID NO: 237 (GTCCTCATGGTTCGTGTTGATGTAG).

[0247] In certain embodiments, the targeting sequence is selected from: SEQ ID NO: 225 (TTCGTGTTGATGTAGGACTG); SEQ ID NO: 226 (GTTCGTGTTGATGTAGGACTG); SEQ ID NO: 227 (GGTTCGTGTTGATGTAGGACTG); SEQ ID NO: 228 (TGGTTCGTGTTGATGTAGGACTG); SEQ ID NO: 229 (ATGGTTCGTGTTGATGTAGGACTG); SEQ ID NO: 230 (CATGGTTCGTGTTGATGTAGGACTG); SEQ ID NO: 231 (CATGGTTCGTGTTGATGTAGGACT); SEQ ID NO: 232 (CATGGTTCGTGTTGATGTAGGAC); SEQ ID NO: 233 (CATGGTTCGTGTTGATGTAGGA); SEQ ID NO: 234 (CATGGTTCGTGTTGATGTAGG); and SEQ ID NO: 235 (TCCTCATGGTTCGTGTTGATGTAGG).

[0248] In certain embodiments, the targeting sequence is selected from: SEQ ID NO: 231 (CATGGTTCGTGTTGATGTAGGACT); SEQ ID NO: 232 (CATGGTTCGTGTTGATGTAGGAC); SEQ ID NO: 233 (CATGGTTCGTGTTGATGTAGGA); SEQ ID NO: 234 (CATGGTTCGTGTTGATGTAGG); SEQ ID NO: 235 (TCCTCATGGTTCGTGTTGATGTAGG); SEQ ID NO: 236 (CATGGTTCGTGTTGATGTAG); and SEQ ID NO: 237 (GTCCTCATGGTTCGTGTTGATGTAG).

[0249] In certain embodiments, the targeting sequence is SEQ ID NO: 230

[0250] In certain embodiments, the targeting sequence is selected from: SEQ ID NO: 238 (GATGAAGTCCTCATGGTTCGTGTTG); and SEQ ID NO: 239 (CGATGAAGTCCTCATGGTTCGTGTT).

[0251] In certain embodiments, the targeting sequence is selected from: SEQ ID NO: 241 (TACTTGGCAAACCCGATGAAGTCCT); andSEQ ID NO: 242 (CCTACTTGGCAAACCCGATGAAGTC).

[0252] In certain embodiments, the targeting sequence is selected from: SEQ ID NO: 210 (CAGCAGAAGAATCTGGBGGAGAGCG); SEQ ID NO: 211 (CAATGTCGATCAGCAGAAGAATCTG); SEQ ID NO: 240 (CAAACCCGATGAAGTCCTCATGGTT); and SEQ ID NO: 243 (AAGTACCTACTTGGCAAACCCGATG).

[0253] In certain embodiments, the target region is within the exon internal region of exon 13 (SEQ ID NO: 8), the intron 12 / exon 13 junction, the exon 13 / intron 13 junction, or the intron internal region of intron 12 (SEQ ID NO: 12).

[0254] In certain embodiments, the target region of the human DNM2 gene pre-mRNA is within the 27thnucleotide of intron 12 measured from the 5′ end of exon 13 (SEQ ID NO: 8) to the 12thnucleotide of exon 13 measured from the 5′ end of exon 13. In certain embodiments, the target region is a region within SEQ ID NO: 46. In certain embodiments, the target region of the human DNM2 gene pre-mRNA is within DNM2 H13A(-27+12).

[0255] In certain embodiments, the target region of the human DNM2 gene pre-mRNA is within the 27thnucleotide of intron 12 measured from the 5′ end of exon 13 (SEQ ID NO: 8) to the 2ndnucleotide of exon 13 measured from the 5′ end of exon 13. In certain embodiments, the target region is a region within SEQ ID NO: 47. In certain embodiments, the target region is a region within DNM2 H13A(-27+2).

[0256] In certain embodiments, the target region of the human DNM2 gene pre-mRNA is within the 22ndnucleotide of intron 12 measured from the 5′ end of exon 13 (SEQ ID NO: 8) to the 7thnucleotide of exon 13 measured from the 5′ end of exon 13. In certain embodiments, the target region is a region within SEQ ID NO: 48. In certain embodiments, the target region is a region within DNM2 H13A(-22+7).

[0257] In certain embodiments, the target region of the human DNM2 gene pre-mRNA is within the 17thnucleotide of intron 12 measured from the 5′ end of exon 13 (SEQ ID NO: 8) to the 12thnucleotide of exon 13 measured from the 5′ end of exon 13. In certain embodiments, the target region is a region within SEQ ID NO: 49. In certain embodiments, the target region is a region within DNM2 H13A(-17+12).

[0258] In certain embodiments, the target region of the human DNM2 gene pre-mRNA is within the 11thnucleotide of intron 12 (SEQ ID NO: 12) measured from the 5′ end of exon 13 (SEQ ID NO: 8) to the 24thnucleotide of exon 13 measured from the 5′ end of exon 13. In certain embodiments, the target region is a region within SEQ ID NO: 50. In certain embodiments, the target region is a region within DNM2 H13A(-11+24).

[0259] In certain embodiments, the target region of the human DNM2 gene pre-mRNA is within the 11thnucleotide of intron 12 measured from the 5′ end of exon 13 (SEQ ID NO: 8) to the 18thnucleotide of exon 13 measured from the 5′ end of exon 13. In certain embodiments, the target region is a region within SEQ ID NO: 51. In certain embodiments, the target region is a region within DNM2 H13A(-11+18).

[0260] In certain embodiments, the target region of the human DNM2 gene pre-mRNA is within the 5thnucleotide of intron 12 measured from the 5′ end of exon 13 (SEQ ID NO: 8) to the 24thnucleotide exon 13 measured from the 5′ end of exon 13. In certain embodiments, the target region is a region within SEQ ID NO: 52. In certain embodiments, the target region is a region within DNM2 H13A(-5+24).

[0261] In certain embodiments, the target region of the human DNM2 gene pre-mRNA is within the 8thnucleotide of intron 12 measured from the 5′ end of exon 13 (SEQ ID NO: 8) to the 21stnucleotide exon 13 measured from the 5′ end of exon 13. In certain embodiments, the target region is a region within SEQ ID NO: 53. In certain embodiments, the target region is a region within DNM2 H13A(-8+21).

[0262] In certain embodiments, the target region of the human DNM2 gene pre-mRNA is within the 1st nucleotide to the 30th nucleotide of exon 13 measured from the 5′ end of exon 13 (SEQ ID NO: 8). In certain embodiments, the target region is a region within SEQ ID NO: 54. In certain embodiments, the target region is a region within DNM2 H13A(+1+30).

[0263] In certain embodiments, the target region of the human DNM2 gene pre-mRNA is within the 1st nucleotide to the 28th nucleotide of exon 13 measured from the 5′ end of exon 13 (SEQ ID NO: 8). In certain embodiments, the target region is a region within SEQ ID NO: 55. In certain embodiments, the target region is a region within DNM2 H13A(+1+28).

[0264] In certain embodiments, the target region of the human DNM2 gene pre-mRNA is within the 6th nucleotide to the 30th nucleotide of exon 13 measured from the 5′ end of exon 13 (SEQ ID NO: 8). In certain embodiments, the target region is a region within SEQ ID NO: 56. In certain embodiments, the target region is a region within DNM2 H13A(+6+30).

[0265] In certain embodiments, the target region of the human DNM2 gene pre-mRNA is within the 3rd nucleotide to the 30th nucleotide of exon 13 measured from the 5′ end of exon 13 (SEQ ID NO: 8). In certain embodiments, the target region is a region within SEQ ID NO: 57. In certain embodiments, the target region is a region within DNM2 H13A(+3+30).

[0266] In certain embodiments, the target region of the human DNM2 gene pre-mRNA is DNM2 H13A(-27-3), DNM2 H13A(-26-2), DNM2 H13A(-25-1), DNM2 H13A(-24+1), DNM2 H13A(- 23+2), DNM2 H13A(-22+3), DNM2 H13A(-21+4), DNM2 H13A(-20+5), DNM2 H13A(-19+6), DNM2 H13A(-18+7), DNM2 H13A(-17+8), DNM2 H13A(-16+9), DNM2 H13A(-15+10), DNM2H13A(-14+11), DNM2 H13A(-13+12), DNM2 H13A(-11+14), DNM2 H13A(-10+15), DNM2 H13A(-9+16), DNM2 H13A(-8+17), DNM2 H13A(-7+18), DNM2 H13A(-6+19), DNM2 H13A(- 5+20), DNM2 H13A(-4+21), DNM2 H13A(-3+22), DNM2 H13A(-2+23), DNM2 H13A(-1+24), DNM2 H13A(+1+25), DNM2 H13A(+2+25), DNM2 H13A(+3+27), DNM2 H13A(+4+23), DNM2 H13A(+4+24), DNM2 H13A(+4+25), DNM2 H13A(+4+26), DNM2 H13A(+4+27), DNM2 H13A(+4+28), DNM2 H13A(+5+28), DNM2 H13A(+6+28), DNM2 H13A(+6+30), DNM2 H13A(+7+28), DNM2 H13A(+8+28), DNM2 H13A(+9+28), DNM2 H13A(+16+40), DNM2 H13D(+22-3), or DNM2 H13D(+7-18).

[0267] In certain embodiments, the target region of the human DNM2 gene pre-mRNA is DNM2 H13A(-27-3), DNM2 H13A(-26-2), DNM2 H13A(-25-1), DNM2 H13A(-24+1), DNM2 H13A(- 23+2), DNM2 H13A(-22+3), DNM2 H13A(-21+4), DNM2 H13A(-20+5), DNM2 H13A(-19+6), DNM2 H13A(-18+7), DNM2 H13A(-17+8), DNM2 H13A(-16+9), DNM2 H13A(-15+10), DNM2 H13A(-14+11), DNM2 H13A(-13+12), DNM2 H13A(-11+14), DNM2 H13A(-10+15), DNM2 H13A(-9+16), DNM2 H13A(-8+17), DNM2 H13A(-7+18), DNM2 H13A(-6+19), DNM2 H13A(- 5+20), DNM2 H13A(-4+21), DNM2 H13A(-3+22), DNM2 H13A(-2+23), DNM2 H13A(-1+24), DNM2 H13A(+1+25), DNM2 H13A(+2+25), DNM2 H13A(+3+27), or DNM2 H13A(+4+28).

[0268] In certain embodiments, the target region of the human DNM2 gene pre-mRNA is DNM2 H13A(-27-3), DNM2 H13A(-26-2), DNM2 H13A(-25-1), DNM2 H13A(-24+1), DNM2 H13A(- 23+2), DNM2 H13A(-22+3), DNM2 H13A(-21+4), DNM2 H13A(-20+5), DNM2 H13A(-19+6), DNM2 H13A(-18+7), DNM2 H13A(-17+8), DNM2 H13A(-16+9), DNM2 H13A(-15+10), DNM2 H13A(-14+11), or DNM2 H13A(-13+12).

[0269] In certain embodiments, the target region of the human DNM2 gene pre-mRNA is DNM2 H13A(-27-3), DNM2 H13A(-26-2), DNM2 H13A(-25-1), DNM2 H13A(-24+1), or DNM2 H13A(- 23+2).

[0270] In certain embodiments, the target region of the human DNM2 gene pre-mRNA is DNM2 H13A(-22+3), DNM2 H13A(-21+4), DNM2 H13A(-20+5), DNM2 H13A(-19+6), or DNM2 H13A(- 18+7).

[0271] In certain embodiments, the target region of the human DNM2 gene pre-mRNA is DNM2 H13A(-17+8), DNM2 H13A(-16+9), DNM2 H13A(-15+10), DNM2 H13A(-14+11), or DNM2 H13A(-13+12).

[0272] In certain embodiments, the target region of the human DNM2 gene pre-mRNA is DNM2 H13A(-11+14), DNM2 H13A(-10+15), DNM2 H13A(-9+16), DNM2 H13A(-8+17), DNM2 H13A(- 7+18), DNM2 H13A(-6+19), DNM2 H13A(-5+20), DNM2 H13A(-4+21), DNM2 H13A(-3+22), DNM2 H13A(-2+23), or DNM2 H13A(-1+24).

[0273] In certain embodiments, the target region of the human DNM2 gene pre-mRNA is DNM2 H13A(-11+14), DNM2 H13A(-10+15), DNM2 H13A(-9+16), DNM2 H13A(-8+17), or DNM2 H13A(-7+18).

[0274] In certain embodiments, the target region of the human DNM2 gene pre-mRNA is DNM2 H13A(-5+20), DNM2 H13A(-4+21), DNM2 H13A(-3+22), DNM2 H13A(-2+23), or DNM2 H13A(- 1+24).

[0275] In certain embodiments, the target region of the human DNM2 gene pre-mRNA is DNM2 H13A(-8+17), DNM2 H13A(-7+18), DNM2 H13A(-6+19), DNM2 H13A(-5+20), or DNM2 H13A(- 4+21).

[0276] In certain embodiments, the target region of the human DNM2 gene pre-mRNA is DNM2 H13A(+1+25), DNM2 H13A(+2+25), DNM2 H13A(+3+27), DNM2 H13A(+4+23), DNM2 H13A(+4+24), DNM2 H13A(+4+25), DNM2 H13A(+4+26), DNM2 H13A(+4+27), DNM2 H13A(+4+28), DNM2 H13A(+5+28), DNM2 H13A(+6+28), DNM2 H13A(+6+30), DNM2 H13A(+7+28), DNM2 H13A(+8+28), or DNM2 H13A(+9+28).

[0277] In certain embodiments, the target region of the human DNM2 gene pre-mRNA is DNM2 H13A(+1+25), DNM2 H13A(+2+25), DNM2 H13A(+3+27), DNM2 H13A(+4+23), DNM2 H13A(+4+24), DNM2 H13A(+4+25), DNM2 H13A(+4+26), DNM2 H13A(+4+27), DNM2 H13A(+4+28), or DNM2 H13A(+5+28).

[0278] In certain embodiments, the target region of the human DNM2 gene pre-mRNA is DNM2 H13A(+6+28), DNM2 H13A(+6+30), DNM2 H13A(+7+28), DNM2 H13A(+8+28), or DNM2 H13A(+9+28).

[0279] In certain embodiments, the target region of the human DNM2 gene pre-mRNA is DNM2 H13A(+3+27), DNM2 H13A(+4+23), DNM2 H13A(+4+24), DNM2 H13A(+4+25), DNM2 H13A(+4+26), DNM2 H13A(+4+27), DNM2 H13A(+4+28), DNM2 H13A(+5+28), DNM2 H13A(+6+28), or DNM2 H13A(+6+30).

[0280] In certain embodiments, the target region of the human DNM2 gene pre-mRNA DNM2 H13A(+4+28). In certain embodiments, the target region of the human DNM2 gene pre-mRNA is DNM2 H13A(+16+40). In certain embodiments, the target region of the human DNM2 gene pre- mRNA is DNM2 H13D(+22-3). In certain embodiments, the target region of the human DNM2 gene pre-mRNA is DNM2 H13D(+7-18).

[0281] In certain embodiments, the targeting sequence is selected from: SEQ ID NO: 244 (GAAACCAAAGAACAGACAGGGTTCA); SEQ ID NO: 245 (TGAAACCAAAGAACAGACAGGGTTC); SEQ ID NO: 246 (CTGAAACCAAAGAACAGACAGGGTT); SEQ ID NO: 247 (ACTGAAACCAAAGAACAGACAGGGT);SEQ ID NO: 248 (CACTGAAACCAAAGAACAGACAGGG); SEQ ID NO: 249 (GCACTGAAACCAAAGAACAGACAGG); SEQ ID NO: 250 (GGCACTGAAACCAAAGAACAGACAG); SEQ ID NO: 251 (GGGCACTGAAACCAAAGAACAGACA); SEQ ID NO: 252 (TGGGCACTGAAACCAAAGAACAGAC); SEQ ID NO: 253 (CTGGGCACTGAAACCAAAGAACAGA); SEQ ID NO: 254 (GCTGGGCACTGAAACCAAAGAACAG); SEQ ID NO: 255 (TGCTGGGCACTGAAACCAAAGAACA); SEQ ID NO: 256 (CTGCTGGGCACTGAAACCAAAGAAC); SEQ ID NO: 257 (TCTGCTGGGCACTGAAACCAAAGAA); SEQ ID NO: 258 (CTCTGCTGGGCACTGAAACCAAAGA); SEQ ID NO: 259 (TCCTCTGCTGGGCACTGAAACCAAA); SEQ ID NO: 260 (CTCCTCTGCTGGGCACTGAAACCAA); SEQ ID NO: 261 (GCTCCTCTGCTGGGCACTGAAACCA); SEQ ID NO: 262 (TGCTCCTCTGCTGGGCACTGAAACC); SEQ ID NO: 263 (GTGCTCCTCTGCTGGGCACTGAAAC); SEQ ID NO: 264 (CGTGCTCCTCTGCTGGGCACTGAAA); SEQ ID NO: 265 (GCGTGCTCCTCTGCTGGGCACTGAA); SEQ ID NO: 266 (TGCGTGCTCCTCTGCTGGGCACTGA); SEQ ID NO: 267 (CTGCGTGCTCCTCTGCTGGGCACTG); SEQ ID NO: 268 (GCTGCGTGCTCCTCTGCTGGGCACT); SEQ ID NO: 269 (AGCTGCGTGCTCCTCTGCTGGGCAC); SEQ ID NO: 270 (CAGCTGCGTGCTCCTCTGCTGGGCA); SEQ ID NO: 271 (TCAGCTGCGTGCTCCTCTGCTGGGC); SEQ ID NO: 272 (TTCAGCTGCGTGCTCCTCTGCTGGG); SEQ ID NO: 273 (GCTGCGTGCTCCTCTGCTGG); SEQ ID NO: 274 (AGCTGCGTGCTCCTCTGCTGG); SEQ ID NO: 275 (CAGCTGCGTGCTCCTCTGCTGG); SEQ ID NO: 276 (TCAGCTGCGTGCTCCTCTGCTGG); SEQ ID NO: 277 (TTCAGCTGCGTGCTCCTCTGCTGG); SEQ ID NO: 278 (GTTCAGCTGCGTGCTCCTCTGCTGG); SEQ ID NO: 279 (GTTCAGCTGCGTGCTCCTCTGCTG); SEQ ID NO: 280 (GTTCAGCTGCGTGCTCCTCTGCT); SEQ ID NO: 281 (TTGTTCAGCTGCGTGCTCCTCTGCT); SEQ ID NO: 282 (GTTCAGCTGCGTGCTCCTCTGC);SEQ ID NO: 283 (GTTCAGCTGCGTGCTCCTCTG); SEQ ID NO: 284 (GTTCAGCTGCGTGCTCCTCT); SEQ ID NO: 285 (GGCTCTCTTCTTGTTCAGCTGCGTG); SEQ ID NO: 286 (TACCTGATTGGBGATGGCTCTCTTC); and SEQ ID NO: 287 (TGCAGAGGBGTGTGCTACCTGATTG), wherein “B” represents an abasic subunit or guanine. In certain embodiments, B is an abasic subunit.

[0282] In certain embodiments, the targeting sequence is selected from: SEQ ID NO: 244 (GAAACCAAAGAACAGACAGGGTTCA); SEQ ID NO: 245 (TGAAACCAAAGAACAGACAGGGTTC); SEQ ID NO: 246 (CTGAAACCAAAGAACAGACAGGGTT); SEQ ID NO: 247 (ACTGAAACCAAAGAACAGACAGGGT); SEQ ID NO: 248 (CACTGAAACCAAAGAACAGACAGGG); SEQ ID NO: 249 (GCACTGAAACCAAAGAACAGACAGG); SEQ ID NO: 250 (GGCACTGAAACCAAAGAACAGACAG); SEQ ID NO: 251 (GGGCACTGAAACCAAAGAACAGACA); SEQ ID NO: 252 (TGGGCACTGAAACCAAAGAACAGAC); SEQ ID NO: 253 (CTGGGCACTGAAACCAAAGAACAGA); SEQ ID NO: 254 (GCTGGGCACTGAAACCAAAGAACAG); SEQ ID NO: 255 (TGCTGGGCACTGAAACCAAAGAACA); SEQ ID NO: 256 (CTGCTGGGCACTGAAACCAAAGAAC); SEQ ID NO: 257 (TCTGCTGGGCACTGAAACCAAAGAA); SEQ ID NO: 258 (CTCTGCTGGGCACTGAAACCAAAGA); SEQ ID NO: 259 (TCCTCTGCTGGGCACTGAAACCAAA); SEQ ID NO: 260 (CTCCTCTGCTGGGCACTGAAACCAA); SEQ ID NO: 261 (GCTCCTCTGCTGGGCACTGAAACCA); SEQ ID NO: 262 (TGCTCCTCTGCTGGGCACTGAAACC); SEQ ID NO: 263 (GTGCTCCTCTGCTGGGCACTGAAAC); SEQ ID NO: 264 (CGTGCTCCTCTGCTGGGCACTGAAA); SEQ ID NO: 265 (GCGTGCTCCTCTGCTGGGCACTGAA); SEQ ID NO: 266 (TGCGTGCTCCTCTGCTGGGCACTGA); SEQ ID NO: 267 (CTGCGTGCTCCTCTGCTGGGCACTG); SEQ ID NO: 268 (GCTGCGTGCTCCTCTGCTGGGCACT); SEQ ID NO: 269 (AGCTGCGTGCTCCTCTGCTGGGCAC); SEQ ID NO: 270 (CAGCTGCGTGCTCCTCTGCTGGGCA); SEQ ID NO: 271 (TCAGCTGCGTGCTCCTCTGCTGGGC);SEQ ID NO: 272 (TTCAGCTGCGTGCTCCTCTGCTGGG); SEQ ID NO: 273 (GCTGCGTGCTCCTCTGCTGG); SEQ ID NO: 274 (AGCTGCGTGCTCCTCTGCTGG); SEQ ID NO: 275 (CAGCTGCGTGCTCCTCTGCTGG); SEQ ID NO: 276 (TCAGCTGCGTGCTCCTCTGCTGG); SEQ ID NO: 277 (TTCAGCTGCGTGCTCCTCTGCTGG); and SEQ ID NO: 278 (GTTCAGCTGCGTGCTCCTCTGCTGG).

[0283] In certain embodiments, the targeting sequence is selected from: SEQ ID NO: 244 (GAAACCAAAGAACAGACAGGGTTCA); SEQ ID NO: 245 (TGAAACCAAAGAACAGACAGGGTTC); SEQ ID NO: 246 (CTGAAACCAAAGAACAGACAGGGTT); SEQ ID NO: 247 (ACTGAAACCAAAGAACAGACAGGGT); SEQ ID NO: 248 (CACTGAAACCAAAGAACAGACAGGG); SEQ ID NO: 249 (GCACTGAAACCAAAGAACAGACAGG); SEQ ID NO: 250 (GGCACTGAAACCAAAGAACAGACAG); SEQ ID NO: 251 (GGGCACTGAAACCAAAGAACAGACA); SEQ ID NO: 252 (TGGGCACTGAAACCAAAGAACAGAC); SEQ ID NO: 253 (CTGGGCACTGAAACCAAAGAACAGA); SEQ ID NO: 254 (GCTGGGCACTGAAACCAAAGAACAG); SEQ ID NO: 255 (TGCTGGGCACTGAAACCAAAGAACA); SEQ ID NO: 256 (CTGCTGGGCACTGAAACCAAAGAAC); SEQ ID NO: 257 (TCTGCTGGGCACTGAAACCAAAGAA); and SEQ ID NO: 258 (CTCTGCTGGGCACTGAAACCAAAGA).

[0284] In certain embodiments, the targeting sequence is selected from: SEQ ID NO: 244 (GAAACCAAAGAACAGACAGGGTTCA); SEQ ID NO: 245 (TGAAACCAAAGAACAGACAGGGTTC); SEQ ID NO: 246 (CTGAAACCAAAGAACAGACAGGGTT); SEQ ID NO: 247 (ACTGAAACCAAAGAACAGACAGGGT); and SEQ ID NO: 248 (CACTGAAACCAAAGAACAGACAGGG).

[0285] In certain embodiments, the targeting sequence is selected from: SEQ ID NO: 249 (GCACTGAAACCAAAGAACAGACAGG); SEQ ID NO: 250 (GGCACTGAAACCAAAGAACAGACAG); SEQ ID NO: 251 (GGGCACTGAAACCAAAGAACAGACA); SEQ ID NO: 252 (TGGGCACTGAAACCAAAGAACAGAC); and SEQ ID NO: 253 (CTGGGCACTGAAACCAAAGAACAGA).

[0286] In certain embodiments, the targeting sequence is selected from: SEQ ID NO: 254 (GCTGGGCACTGAAACCAAAGAACAG); SEQ ID NO: 255 (TGCTGGGCACTGAAACCAAAGAACA); SEQ ID NO: 256 (CTGCTGGGCACTGAAACCAAAGAAC); SEQ ID NO: 257 (TCTGCTGGGCACTGAAACCAAAGAA); and SEQ ID NO: 258 (CTCTGCTGGGCACTGAAACCAAAGA).

[0287] In certain embodiments, the targeting sequence is selected from: SEQ ID NO: 259 (TCCTCTGCTGGGCACTGAAACCAAA); SEQ ID NO: 260 (CTCCTCTGCTGGGCACTGAAACCAA); SEQ ID NO: 261 (GCTCCTCTGCTGGGCACTGAAACCA); SEQ ID NO: 262 (TGCTCCTCTGCTGGGCACTGAAACC); SEQ ID NO: 263 (GTGCTCCTCTGCTGGGCACTGAAAC); SEQ ID NO: 264 (CGTGCTCCTCTGCTGGGCACTGAAA); SEQ ID NO: 265 (GCGTGCTCCTCTGCTGGGCACTGAA); SEQ ID NO: 266 (TGCGTGCTCCTCTGCTGGGCACTGA); SEQ ID NO: 267 (CTGCGTGCTCCTCTGCTGGGCACTG); SEQ ID NO: 268 (GCTGCGTGCTCCTCTGCTGGGCACT); and SEQ ID NO: 269 (AGCTGCGTGCTCCTCTGCTGGGCAC).

[0288] In certain embodiments, the targeting sequence is selected from: SEQ ID NO: 259 (TCCTCTGCTGGGCACTGAAACCAAA); SEQ ID NO: 260 (CTCCTCTGCTGGGCACTGAAACCAA); SEQ ID NO: 261 (GCTCCTCTGCTGGGCACTGAAACCA); SEQ ID NO: 262 (TGCTCCTCTGCTGGGCACTGAAACC); and SEQ ID NO: 263 (GTGCTCCTCTGCTGGGCACTGAAAC).

[0289] In certain embodiments, the targeting sequence is selected from: SEQ ID NO: 265 (GCGTGCTCCTCTGCTGGGCACTGAA); SEQ ID NO: 266 (TGCGTGCTCCTCTGCTGGGCACTGA); SEQ ID NO: 267 (CTGCGTGCTCCTCTGCTGGGCACTG); SEQ ID NO: 268 (GCTGCGTGCTCCTCTGCTGGGCACT); and SEQ ID NO: 269 (AGCTGCGTGCTCCTCTGCTGGGCAC).

[0290] In certain embodiments, the targeting sequence is selected from: SEQ ID NO: 262 (TGCTCCTCTGCTGGGCACTGAAACC); SEQ ID NO: 263 (GTGCTCCTCTGCTGGGCACTGAAAC); SEQ ID NO: 264 (CGTGCTCCTCTGCTGGGCACTGAAA); and SEQ ID NO: 265 (GCGTGCTCCTCTGCTGGGCACTGAA).

[0291] In certain embodiments, the targeting sequence is selected from: SEQ ID NO: 270 (CAGCTGCGTGCTCCTCTGCTGGGCA); SEQ ID NO: 271 (TCAGCTGCGTGCTCCTCTGCTGGGC); SEQ ID NO: 272 (TTCAGCTGCGTGCTCCTCTGCTGGG); SEQ ID NO: 273 (GCTGCGTGCTCCTCTGCTGG); SEQ ID NO: 274 (AGCTGCGTGCTCCTCTGCTGG); SEQ ID NO: 275 (CAGCTGCGTGCTCCTCTGCTGG); SEQ ID NO: 276 (TCAGCTGCGTGCTCCTCTGCTGG); SEQ ID NO: 277 (TTCAGCTGCGTGCTCCTCTGCTGG); SEQ ID NO: 278 (GTTCAGCTGCGTGCTCCTCTGCTGG); SEQ ID NO: 279 (GTTCAGCTGCGTGCTCCTCTGCTG); SEQ ID NO: 280 (GTTCAGCTGCGTGCTCCTCTGCT); SEQ ID NO: 281 (TTGTTCAGCTGCGTGCTCCTCTGCT); SEQ ID NO: 282 (GTTCAGCTGCGTGCTCCTCTGC); SEQ ID NO: 283 (GTTCAGCTGCGTGCTCCTCTG); and SEQ ID NO: 284 (GTTCAGCTGCGTGCTCCTCT).

[0292] In certain embodiments, the targeting sequence is selected from: SEQ ID NO: 270 (CAGCTGCGTGCTCCTCTGCTGGGCA); SEQ ID NO: 271 (TCAGCTGCGTGCTCCTCTGCTGGGC); SEQ ID NO: 272 (TTCAGCTGCGTGCTCCTCTGCTGGG); SEQ ID NO: 273 (GCTGCGTGCTCCTCTGCTGG); SEQ ID NO: 274 (AGCTGCGTGCTCCTCTGCTGG); SEQ ID NO: 275 (CAGCTGCGTGCTCCTCTGCTGG); SEQ ID NO: 276 (TCAGCTGCGTGCTCCTCTGCTGG); SEQ ID NO: 277 (TTCAGCTGCGTGCTCCTCTGCTGG); SEQ ID NO: 278 (GTTCAGCTGCGTGCTCCTCTGCTGG); and SEQ ID NO: 279 (GTTCAGCTGCGTGCTCCTCTGCTG).

[0293] In certain embodiments, the targeting sequence is selected from: SEQ ID NO: 280 (GTTCAGCTGCGTGCTCCTCTGCT); SEQ ID NO: 281 (TTGTTCAGCTGCGTGCTCCTCTGCT); SEQ ID NO: 282 (GTTCAGCTGCGTGCTCCTCTGC); SEQ ID NO: 283 (GTTCAGCTGCGTGCTCCTCTG); and SEQ ID NO: 284 (GTTCAGCTGCGTGCTCCTCT).

[0294] In certain embodiments, the targeting sequence is selected from: SEQ ID NO: 272 (TTCAGCTGCGTGCTCCTCTGCTGGG);SEQ ID NO: 273 (GCTGCGTGCTCCTCTGCTGG); SEQ ID NO: 274 (AGCTGCGTGCTCCTCTGCTGG); SEQ ID NO: 275 (CAGCTGCGTGCTCCTCTGCTGG); SEQ ID NO: 276 (TCAGCTGCGTGCTCCTCTGCTGG); SEQ ID NO: 277 (TTCAGCTGCGTGCTCCTCTGCTGG); SEQ ID NO: 278 (GTTCAGCTGCGTGCTCCTCTGCTGG); SEQ ID NO: 279 (GTTCAGCTGCGTGCTCCTCTGCTG); SEQ ID NO: 280 (GTTCAGCTGCGTGCTCCTCTGCT); and SEQ ID NO: 281 (TTGTTCAGCTGCGTGCTCCTCTGCT).

[0295] In certain embodiments, the targeting sequence is selected from: SEQ ID NO: 278 (GTTCAGCTGCGTGCTCCTCTGCTGG); SEQ ID NO: 285 (GGCTCTCTTCTTGTTCAGCTGCGTG); SEQ ID NO: 286 (TACCTGATTGGBGATGGCTCTCTTC); and SEQ ID NO: 287 (TGCAGAGGBGTGTGCTACCTGATTG).

[0296] In certain embodiments, the target region is within the exon internal region of exon 6 (SEQ ID NO: 3), the intron 5 / exon 6 junction, the exon 6 / intron 6 junction, or the intron internal region of intron 6 (SEQ ID NO: 11).

[0297] In certain embodiments, the target region of the human DNM2 gene pre-mRNA is within the 10th nucleotide to the 37th nucleotide of exon 6 measured from the 5′ end of exon 6 (SEQ ID NO: 3). In certain embodiments, the target region is a region within SEQ ID NO: 58. In certain embodiments, the target region is a region within DNM2 H6A(+10+37).

[0298] In certain embodiments, the target region of the human DNM2 gene pre-mRNA is within the 32nd nucleotide to the 59th nucleotide of exon 6 measured from the 5′ end of exon 6 (SEQ ID NO: 3). In certain embodiments, the target region is a region within SEQ ID NO: 59. In certain embodiments, the target region is a region within DNM2 H6A(+32+59).

[0299] In certain embodiments, the target region of the human DNM2 gene pre-mRNA is within the 60th nucleotide to the 87th nucleotide of exon 6 measured from the 5′ end of exon 6 (SEQ ID NO: 3). In certain embodiments, the target region is a region within SEQ ID NO: 60. In certain embodiments, the target region is a region within DNM2 H6A(+60+87).

[0300] In certain embodiments, the target region of the human DNM2 gene pre-mRNA is within the 130th nucleotide to the 156th nucleotide measured from the 5′ end of exon 6 (SEQ ID NO: 3). In certain embodiments, the target region is a region within SEQ ID NO: 61. In certain embodiments, the target region is a region within DNM2 H6A(+130+156).

[0301] In certain embodiments, the target region of the human DNM2 gene pre-mRNA is within the 17th nucleotide of exon 6 measured from the 3′ end of exon 6 (SEQ ID NO: 3) to the 10thnucleotide of intron 6 measured from the 3′ end of exon 6. In certain embodiments, the target region is a region within SEQ ID NO: 62. In certain embodiments, the target region is a region within DNM2 H6D(+17-10).

[0302] In certain embodiments, the target region of the human DNM2 gene pre-mRNA is DNM2 H6A(-20+5), DNM2 H6A(-6+19), DNM2 H6A(-2+23), DNM2 H6A(+3+26), DNM2 H6A(+10+3), DNM2 H6A(+13+37), DNM2 H6A(+23+47), DNM2 H6A(+32+56), DNM2 H6A(+35+59), DNM2 H6A(+44+68), DNM2 H6A(+54+78), DNM2 H6A(+60+84), DNM2 H6A(+63+87), DNM2 H6A(+88+112), DNM2 H6A(+96+119), DNM2 H6A(+105+129), DNM2 H6A(+121+145), DNM2 H6A(+130+154), DNM2 H6A(+132+156), DNM2 H6D (+6-19), DNM2 H6D (+15-10), or DNM2 H6D (+17-8).

[0303] In certain embodiments, the target region of the human DNM2 gene pre-mRNA is DNM2 H6A(+10+3) or DNM2 H6A(+13+37).

[0304] In certain embodiments, the target region of the human DNM2 gene pre-mRNA is DNM2 H6A(+32+56) or DNM2 H6A(+35+59).

[0305] In certain embodiments, the target region of the human DNM2 gene pre-mRNA is DNM2 H6A(+60+84) or DNM2 H6A(+63+87).

[0306] In certain embodiments, the target region of the human DNM2 gene pre-mRNA is DNM2 H6A(+130+154) or DNM2 H6A(+132+156).

[0307] In certain embodiments, the target region of the human DNM2 gene pre-mRNA is DNM2 H6D (+15-10) or DNM2 H6D (+17-8). In certain embodiments, the target region of the human DNM2 gene pre-mRNA is DNM2 H6A(-20+5). In certain embodiments, the target region of the human DNM2 gene pre-mRNA is DNM2 H6A(-6+19). In certain embodiments, the target region of the human DNM2 gene pre-mRNA is DNM2 H6A(-2+23). In certain embodiments, the target region of the human DNM2 gene pre-mRNA is DNM2 H6A(+3+26). In certain embodiments, the target region of the human DNM2 gene pre-mRNA is DNM2 H6A(+23+47). In certain embodiments, the target region of the human DNM2 gene pre-mRNA is DNM2 H6A(+44+68). In certain embodiments, the target region of the human DNM2 gene pre-mRNA is DNM2 H6A(+54+78). In certain embodiments, the target region of the human DNM2 gene pre-mRNA is DNM2 H6A(+88+112). In certain embodiments, the target region of the human DNM2 gene pre- mRNA is DNM2 H6A(+96+119). In certain embodiments, the target region of the human DNM2 gene pre-mRNA is DNM2 H6A(+105+129). In certain embodiments, the target region of the human DNM2 gene pre-mRNA is DNM2 H6A(+121+145). In certain embodiments, the target region of the human DNM2 gene pre-mRNA is DNM2 H6D (+6-19).

[0308] In certain embodiments, the targeting sequence is selected from: SEQ ID NO: 97 (GTAGCCTGTGGGGAGAGGCAGTCAG);SEQ ID NO: 98 (TTCACCACGCCAATGTAGCCTGTGG); SEQ ID NO: 99 (GCGGTTCACCACGCCAATGTAGCCT); SEQ ID NO: 100 (GCTGCGGTTCACCACGCCAATGTA); SEQ ID NO: 101 (TCCTTCTGGCTGCGGTTCACCACGC); SEQ ID NO: 102 (ATATCCTTCTGGCTGCGGTTCACCA); SEQ ID NO: 103 (CTTGCCCTCAATATCCTTCTGGCTG); SEQ ID NO: 104 (GATGTCCTTCTTGCCCTCAATATCC); SEQ ID NO: 105 (ACGGATGTCCTTCTTGCCCTCAATA); SEQ ID NO: 106 (CAGTGCTGCACGGATGTCCTTCTTG); SEQ ID NO: 107 (TCTCAGCTGCCAGTGCTGCACGGAT); SEQ ID NO: 108 (ACTTCCTCTCAGCTGCCAGTGCTGC); SEQ ID NO: 109 (AGAACTTCCTCTCAGCTGCCAGTGC); SEQ ID NO: 110 (TGCCGGTAGGCCGGGTGGGAGAGGA); SEQ ID NO: 111 (GGCCATGTGCCGGTAGGCCGGGTG); SEQ ID NO: 112 (CCATGCGGTCGGCCATGTGCCGGTA); SEQ ID NO: 113 (TGCAGATGTGGCGTGCCCATGCGGT); SEQ ID NO: 114 (AGCGTCTTCTGCAGATGTGGCGTGC); SEQ ID NO: 115 (TCAGCGTCTTCTGCAGATGTGGCGT); SEQ ID NO: 116 (GTGCAAACCCTTGCAGTACCTGATT); SEQ ID NO: 117 (CTTGCAGTACCTGATTCAGCGTCTT); and SEQ ID NO: 118 (TGCAGTACCTGATTCAGCGTCTTCT).

[0309] In certain embodiments, the target region is within the exon internal region of exon 7 (SEQ ID NO: 4), the intron 6 / exon 7 junction, or the exon 7 / intron 7 junction.

[0310] In certain embodiments, the target region of the human DNM2 gene pre-mRNA is within the 72nd nucleotide to the 98th nucleotide of exon 7 measured from the 5′ end of exon 7 (SEQ ID NO: 4). In certain embodiments, the target region is a region within SEQ ID NO: 63. In certain embodiments, the target region is a region within DNM2 H7A(+72+98).

[0311] In certain embodiments, the target region of the human DNM2 gene pre-mRNA is within the 9th nucleotide of exon 7 measured from the 3′ end of exon 7 (SEQ ID NO: 4) to the 16th nucleotide of intron 7 measured from the 3′ end of exon 7. In certain embodiments, the target region is a region within SEQ ID NO: 64. In certain embodiments, the target region is a region within DNM2 H7D(+9-16).

[0312] In certain embodiments, the target region of the human DNM2 gene pre-mRNA is DNM2 H7A(+1+25), DNM2 H7A(+6+30), DNM2 H7A(+11+35), DNM2 H7A(+22+46), DNM2 H7A(+29+53), DNM2 H7A(+41+65), DNM2 H7A(+51+75), DNM2 H7A(+57+81), DNM2H7A(+62+86), DNM2 H7A(+72+96), DNM2 H7A(+74+98), DNM2 H7A(+81+105), DNM2 H7A(+91+115), or DNM2 H7A(+110+134).

[0313] In certain embodiments, the target region of the human DNM2 gene pre-mRNA is DNM2 H7A(+72+96) or DNM2 H7A(+74+98).

[0314] In certain embodiments, the target region of the human DNM2 gene pre-mRNA is DNM2 H7D(+8-16) or DNM2 H7D(+9-16).

[0315] In certain embodiments, the target region of the human DNM2 gene pre-mRNA is DNM2 H7A(-15+10). In certain embodiments, the target region of the human DNM2 gene pre-mRNA is DNM2 H7A(-5+20). In certain embodiments, the target region of the human DNM2 gene pre- mRNA is DNM2 H7A(+1+25). In certain embodiments, the target region of the human DNM2 gene pre-mRNA is DNM2 H7A(+6+30). In certain embodiments, the target region of the human DNM2 gene pre-mRNA is DNM2 H7A(+11+35). In certain embodiments, the target region of the human DNM2 gene pre-mRNA is DNM2 H7A(+22+46). In certain embodiments, the target region of the human DNM2 gene pre-mRNA is DNM2 H7A(+29+53). In certain embodiments, the target region of the human DNM2 gene pre-mRNA is DNM2 H7A(+41+65). In certain embodiments, the target region of the human DNM2 gene pre-mRNA is DNM2 H7A(+51+75). In certain embodiments, the target region of the human DNM2 gene pre-mRNA is DNM2 H7A(+57+81). In certain embodiments, the target region of the human DNM2 gene pre-mRNA is DNM2 H7A(+62+86). In certain embodiments, the target region of the human DNM2 gene pre- mRNA is DNM2 H7A(+81+105). In certain embodiments, the target region of the human DNM2 gene pre-mRNA is DNM2 H7A(+91+115). In certain embodiments, the target region of the human DNM2 gene pre-mRNA is DNM2 H7A(+110+134). In certain embodiments, the target region of the human DNM2 gene pre-mRNA is DNM2 H7D(+21-4).

[0316] In certain embodiments, the targeting sequence is selected from: SEQ ID NO: 119 (TGGTCAGTTGCTGCAGGAGAGAGGT); SEQ ID NO: 120 (CGGATGTGGTTGGTCAGTTGCTGCA); SEQ ID NO: 121 (ACTCCCGGATGTGGTTGGTCAGTTG); SEQ ID NO: 122 (CAGCGACTCCCGGATGTGGTTGGTC); SEQ ID NO: 123 (GCCGGCAGCGACTCCCGGATGTGGT); SEQ ID NO: 124 (TGCTACGTAGGGCCGGCAGCGACTC); SEQ ID NO: 125 (TGTAGTTTGCTACGTAGGGCCGGCA); SEQ ID NO: 126 (AGCAGCTGGCTCTGTAGTTTGCTAC); SEQ ID NO: 127 (CTCCAGGGACAGCAGCTGGCTCTGT); SEQ ID NO: 128 (CTCCTTCTCCAGGGACAGCAGCTGG); SEQ ID NO: 129 (TCCACCTCCTTCTCCAGGGACAGCA);SEQ ID NO: 130 (CTTGTACTCCTCCACCTCCTTCTCC); SEQ ID NO: 131 (TTCTTGTACTCCTCCACCTCCTTCT); SEQ ID NO: 132 (CCGAAAGTTCTTGTACTCCTCCACC); SEQ ID NO: 133 (GGTCGTCGGGCCGAAAGTTCTTGTA); SEQ ID NO: 134 (GCTTTGGTTTTGCGGGTGGGGTCGT); SEQ ID NO: 135 (GTGCCGBGGTACATACTGCAGCAG); SEQ ID NO: 136 (GTGCCGGGGTACATACTGCAGCAGG); and SEQ ID NO: 137 (ATACTGCAGCAGGGCTTTGGTTTTG), wherein “B” represents an abasic subunit or guanine. In certain embodiments, B is an abasic subunit.

[0317] In certain embodiments, the target region is within the exon internal region of exon 8 (SEQ ID NO: 5), the intron 7 / exon 8 junction, or the exon 8 / intron 8 junction.

[0318] In certain embodiments, the target region of the human DNM2 gene pre-mRNA is within the 7th nucleotide of intron 7 measured from the 5′ end of exon 8 (SEQ ID NO: 5) to the 19th nucleotide of exon 8 measured from the 5′ end of exon 8. In certain embodiments, the target region is a region within SEQ ID NO: 65. In certain embodiments, the target region is a region within DNM2 H8A(-7+19).

[0319] In certain embodiments, the target region of the human DNM2 gene pre-mRNA is within the 18th nucleotide to the 45th nucleotide of exon 8 measured from the 5′ end of exon 8 (SEQ ID NO: 5). In certain embodiments, the target region is a region within SEQ ID NO: 66. In certain embodiments, the target region is a region within DNM2 H8A(+18+45).

[0320] In certain embodiments, the target region of the human DNM2 gene pre-mRNA is DNM2 H8A(-20+5), DNM2 H8A(-14+11), DNM2 H8A(-7+18), DNM2 H8A(-6+19), DNM2 H8A(-2+23), DNM2 H8A(+5+29), DNM2 H8A(+18+42), DNM2 H8A(+21+45), DNM2 H8A(+27+51), DNM2 H8A(+36+60), DNM2 H8A(+46+70), DNM2 H8A(+51+75), DNM2 H8A(+56+80), DNM2 H8A(+65+88), DNM2 H8A(+76+100), DNM2 H8A(+83+107), DNM2 H8A(+96+119), DNM2 H8A(+105+129), DNM2 H8D(+18-7), or DNM2 H8D(+10-15).

[0321] In certain embodiments, the target region of the human DNM2 gene pre-mRNA is DNM2 H8A(-7+18) or DNM2 H8A(-6+19).

[0322] In certain embodiments, the target region of the human DNM2 gene pre-mRNA is DNM2 H8A(+18+42) or DNM2 H8A(+21+45).

[0323] In certain embodiments, the target region of the human DNM2 gene pre-mRNA is DNM2 H8A(-20+5). In certain embodiments, the target region of the human DNM2 gene pre-mRNA is DNM2 H8A(-14+11). In certain embodiments, the target region of the human DNM2 gene pre- mRNA is DNM2 H8A(-2+23). In certain embodiments, the target region of the human DNM2gene pre-mRNA is DNM2 H8A(+5+29). In certain embodiments, the target region of the human DNM2 gene pre-mRNA is DNM2 H8A(+27+51). In certain embodiments, the target region of the human DNM2 gene pre-mRNA is DNM2 H8A(+36+60). In certain embodiments, the target region of the human DNM2 gene pre-mRNA is DNM2 H8A(+46+70). In certain embodiments, the target region of the human DNM2 gene pre-mRNA is DNM2 H8A(+51+75). In certain embodiments, the target region of the human DNM2 gene pre-mRNA is DNM2 H8A(+56+80). In certain embodiments, the target region of the human DNM2 gene pre-mRNA is DNM2 H8A(+65+88). In certain embodiments, the target region of the human DNM2 gene pre-mRNA is DNM2 H8A(+76+100). In certain embodiments, the target region of the human DNM2 gene pre- mRNA is DNM2 H8A(+83+107). In certain embodiments, the target region of the human DNM2 gene pre-mRNA is DNM2 H8A(+96+119). In certain embodiments, the target region of the human DNM2 gene pre-mRNA is DNM2 H8A(+105+129). In certain embodiments, the target region of the human DNM2 gene pre-mRNA is DNM2 H8D(+18-7). In certain embodiments, the target region of the human DNM2 gene pre-mRNA is DNM2 H8D(+10-15).

[0324] In certain embodiments, the targeting sequence is selected from: SEQ ID NO: 138 (CCATCCTATGAGGAAAAGGAAAAAG); SEQ ID NO: 139 (GCTGGACCATCCTATGAGGAAAAGG); SEQ ID NO: 140 (CCAAACTGCTGGACCATCCTATGAG); SEQ ID NO: 141 (CCCAAACTGCTGGACCATCCTATGA); SEQ ID NO: 142 (CCACCCCAAACTGCTGGACCATCCT); SEQ ID NO: 143 (CAAAATCCACCCCAAACTGCTGGAC); SEQ ID NO: 144 (TCGATCCTCTTCTCAAAATCCACCC); SEQ ID NO: 145 (CCCTCGATCCTCTTCTCAAAATCCA); SEQ ID NO: 146 (CCTGAGCCCTCGATCCTCTTCTCAA); SEQ ID NO: 147 (ACCTGATCTCCTGAGCCCTCGATCC); SEQ ID NO: 148 (CAGAGTGTCCACCTGATCTCCTGAG); SEQ ID NO: 149 (AGCTCCAGAGTGTCCACCTGATCTC); SEQ ID NO: 150 (CGGAGAGCTCCAGAGTGTCCACCTG); SEQ ID NO: 151 (GGCGCCCCCGGAGAGCTCCAGAGT); SEQ ID NO: 152 (GCGATTGATTCGGGCGCCCCCGGAG); SEQ ID NO: 153 (GGAAGATGCGATTGATTCGGGCGCC); SEQ ID NO: 154 (GGAACCGCTCGTGGAAGATGCGAT); SEQ ID NO: 155 (AGCTCAAATGGGAACCGCTCGTGGA); SEQ ID NO: 156 (GCACTACCTTCACCAGCTCAAATGG); and SEQ ID NO: 157 (CCCGGGGGGCACTACCTTCACCAGC).

[0325] In certain embodiments, the target region is within the exon internal region of exon 16 (SEQ ID NO: 9), the intron 15 / exon 16 junction, or the exon 16 / intron 16 junction.

[0326] In certain embodiments, the target region of the human DNM2 gene pre-mRNA is DNM2 H16A(-21+3), DNM2 H16A(-13+12), DNM2 H16A(-6+19), DNM2 H16A(+6+30), DNM2 H16A(+15+39), DNM2 H16A(+26+50), DNM2 H16A(+36+60), DNM2 H16A(+45+69), DNM2 H16A(+55+79), DNM2 H16A(+66+90), DNM2 H16A(+75+99), DNM2 H16A(+82+106), DNM2 H16D(+19-6), or DNM2 H16D(+11-14). DNM2 H16A(-21+3).

[0327] In certain embodiments, the target region of the human DNM2 gene pre-mRNA is DNM2 H16A(-21+3). In certain embodiments, the target region of the human DNM2 gene pre-mRNA is DNM2 H16A(-13+12). In certain embodiments, the target region of the human DNM2 gene pre- mRNA is DNM2 H16A(-6+19). In certain embodiments, the target region of the human DNM2 gene pre-mRNA is DNM2 H16A(+6+30). In certain embodiments, the target region of the human DNM2 gene pre-mRNA is DNM2 H16A(+15+39). In certain embodiments, the target region of the human DNM2 gene pre-mRNA is DNM2 H16A(+26+50). In certain embodiments, the target region of the human DNM2 gene pre-mRNA is DNM2 H16A(+36+60). In certain embodiments, the target region of the human DNM2 gene pre-mRNA is DNM2 H16A(+45+69). In certain embodiments, the target region of the human DNM2 gene pre-mRNA is DNM2 H16A(+55+79). In certain embodiments, the target region of the human DNM2 gene pre-mRNA is DNM2 H16A(+66+90). In certain embodiments, the target region of the human DNM2 gene pre-mRNA is DNM2 H16A(+75+99). In certain embodiments, the target region of the human DNM2 gene pre-mRNA is DNM2 H16A(+82+106). In certain embodiments, the target region of the human DNM2 gene pre-mRNA is DNM2 H16D(+19-6). In certain embodiments, the target region of the human DNM2 gene pre-mRNA is DNM2 H16D(+11-14).

[0328] In certain embodiments, the targeting sequence is selected from: SEQ ID NO: 288 (CTCCTGAGGGTGGAGGGAAAAGAG); SEQ ID NO: 289 (CTTCTCTTTCTCCTGAGGGTGGAGG); SEQ ID NO: 290 (TGTACTTCTTCTCTTTCTCCTGAGG); SEQ ID NO: 291 (CAGAGGCAGCATGTACTTCTTCTCT); SEQ ID NO: 292 (GAGGTTGTCCAGAGGCAGCATGTAC); SEQ ID NO: 293 (TCACGGATCTTGAGGTTGTCCAGAG); SEQ ID NO: 294 (CTTCTCCACATCACGGATCTTGAGG); SEQ ID NO: 295 (CATGAAGCCCTTCTCCACATCACGG); SEQ ID NO: 296 (GCTTGTTGGACATGAAGCCCTTCTC); SEQ ID NO: 297 (GGCGAAGACGTGCTTGTTGGACATG); SEQ ID NO: 298 (GTTGAAGATGGCGAAGACGTGCTTG);SEQ ID NO: 299 (GCTCCGTGTTGAAGATGGCGAAGAC); SEQ ID NO: 300 (CCTCACCTCTGCTCCGTGTTGAAGA); and SEQ ID NO: 301 (CCTGGGCCCCTCACCTCTGCTCCGT).

[0329] In certain embodiments, the target region is within the exon internal region of exon 19 (SEQ ID NO: 9), the intron 18 / exon 19 junction, or the exon 18 / intron 18 junction.

[0330] In certain embodiments, the target region of the human DNM2 gene pre-mRNA is DNM2 H19A(-11+14), DNM2 H19A(-4+21), DNM2 H19A(+1+25), DNM2 H19A(+7+31), DNM2 H19A(+16+40), DNM2 H19A(+26+50), DNM2 H19A(+37+61), DNM2 H19A(+47+71), DNM2 H19A(+56+80), DNM2 H19A(+66+90), DNM2 H19A(+76+100), DNM2 H19A(+86+110), DNM2 H19A(+96+120), DNM2 H19A(+106+130), DNM2 H19A(+117+141), DNM2 H19A(+127+151), DNM2 H19A(+137+161), DNM2 H19A(+147+171), DNM2 H19A(+157+181), DNM2 H19A(+166+189), DNM2 H19A(+191+215), DNM2 H19A(+200+224), DNM2 H19D(+23-2), DNM2 H19D(+17-8), or DNM2 H19D(+10-15).

[0331] In certain embodiments, the target region of the human DNM2 gene pre-mRNA is DNM2 H19A(-11+14). In certain embodiments, the target region of the human DNM2 gene pre-mRNA is DNM2 H19A(-4+21). In certain embodiments, the target region of the human DNM2 gene pre- mRNA is DNM2 H19A(+1+25). In certain embodiments, the target region of the human DNM2 gene pre-mRNA is DNM2 H19A(+7+31). In certain embodiments, the target region of the human DNM2 gene pre-mRNA is DNM2 H19A(+16+40). In certain embodiments, the target region of the human DNM2 gene pre-mRNA is DNM2 H19A(+26+50). In certain embodiments, the target region of the human DNM2 gene pre-mRNA is DNM2 H19A(+37+61). In certain embodiments, the target region of the human DNM2 gene pre-mRNA is DNM2 H19A(+47+71). In certain embodiments, the target region of the human DNM2 gene pre-mRNA is DNM2 H19A(+56+80). In certain embodiments, the target region of the human DNM2 gene pre-mRNA is DNM2 H19A(+66+90). In certain embodiments, the target region of the human DNM2 gene pre-mRNA is DNM2 H19A(+76+100). In certain embodiments, the target region of the human DNM2 gene pre-mRNA is DNM2 H19A(+86+110). In certain embodiments, the target region of the human DNM2 gene pre-mRNA is DNM2 H19A(+96+120). In certain embodiments, the target region of the human DNM2 gene pre-mRNA is DNM2 H19A(+106+130). In certain embodiments, the target region of the human DNM2 gene pre-mRNA is DNM2 H19A(+117+141). In certain embodiments, the target region of the human DNM2 gene pre-mRNA is DNM2 H19A(+127+151). In certain embodiments, the target region of the human DNM2 gene pre- mRNA is DNM2 H19A(+137+161). In certain embodiments, the target region of the human DNM2 gene pre-mRNA is DNM2 H19A(+147+171). In certain embodiments, the target region of the human DNM2 gene pre-mRNA is DNM2 H19A(+157+181). In certain embodiments, thetarget region of the human DNM2 gene pre-mRNA is DNM2 H19A(+166+189). In certain embodiments, the target region of the human DNM2 gene pre-mRNA is DNM2 H19A(+191+215). In certain embodiments, the target region of the human DNM2 gene pre- mRNA is DNM2 H19A(+200+224). In certain embodiments, the target region of the human DNM2 gene pre-mRNA is DNM2 H19D(+23-2). In certain embodiments, the target region of the human DNM2 gene pre-mRNA is DNM2 H19D(+17-8). In certain embodiments, the target region of the human DNM2 gene pre-mRNA is DNM2 H19D(+10-15).

[0332] In certain embodiments, the targeting sequence is selected from: SEQ ID NO: 302 (ATGAAGGCCTTCGTCTGCGGGCAGG); SEQ ID NO: 303 (GTGGTGGATGAAGGCCTTCGTCTGC); SEQ ID NO: 304 (GCTCGTGGTGGATGAAGGCCTTCGT); SEQ ID NO: 305 (CCAGCAGCTCGTGGTGGATGAAGGC); SEQ ID NO: 306 (ATAGGTAGGCCAGCAGCTCGTGGTG); SEQ ID NO: 307 (GCCGAGGAGTATAGGTAGGCCAGCA); SEQ ID NO: 308 (TGCTCTGGTCTGCCGAGGAGTATAG); SEQ ID NO: 309 (TCCATGAGGCTGCTCTGGTCTGCCG); SEQ ID NO: 310 (GCCGACTCCTCCATGAGGCTGCTCT); SEQ ID NO: 311 (TGCCTGGTCAGCCGACTCCTCCATG); SEQ ID NO: 312 (CCCGCCGCTGTGCCTGGTCAGCCGA); SEQ ID NO: 313 (AGCATGTCGTCCCGCCGCTGTGCCT); SEQ ID NO: 314 (GTACATGCGCAGCATGTCGTCCCGC); SEQ ID NO: 315 (TGAGGGCATGGTACATGCGCAGCAT); SEQ ID NO: 316 (GAGCGCCTCCTTGAGGGCATGGTAC); SEQ ID NO: 317 (CGATGATGTTGAGCGCCTCCTTGAG); SEQ ID NO: 318 (CTGATGTCACCGATGATGTTGAGCG); SEQ ID NO: 319 (AGTGCTGGTGCTGATGTCACCGATG); SEQ ID NO: 320 (GCGTGGACACAGTGCTGGTGCTGAT); SEQ ID NO: 321 (GGGTACAGGCGTGGACACAGTGCT); SEQ ID NO: 322 (TGGAGCCAGGTGTCATCGACAGGCG); SEQ ID NO: 323 (CTGGCGCTCTGGAGCCAGGTGTCAT); SEQ ID NO: 324 (ACCTGTGGCTGCTGGCGCTCTGGAG); SEQ ID NO: 325 (TTCCGGACCTGTGGCTGCTGGCGCT); and SEQ ID NO: 326 (ACCAGGCTTCCGGACCTGTGGCTGC).

[0333] In certain embodiments, each R2, taken together, forms a targeting sequence having SEQ ID NO: 83. In certain embodiments, each R2, taken together, forms a targeting sequencehaving SEQ ID NO: 88. In certain embodiments, each R2, taken together, forms a targeting sequence having SEQ ID NO: 172. In certain embodiments, R2, taken together, forms a targeting sequence having SEQ ID NO: 199. In certain embodiments, each R2, taken together, forms a targeting sequence having SEQ ID NO: 230. In certain embodiments, each R2, taken together, forms a targeting sequence having SEQ ID NO: 278.

[0334] In one embodiment, the targeting sequence is at least 70, 71, 72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, 88, 89, 90, 91, 92, 93, 94, 95, 96, 97, 98, or 99 percent complementary to the target region. In another embodiment, the targeting sequence is at least 84%, at least 88%, or at least 92% complementary to the target region. In still another embodiment, the targeting sequence is at least 90% complementary to the target region. In yet another embodiment, the targeting sequence is at least 95% complementary to the target region. In still another embodiment, the targeting sequence is 100% complementary to the target region.

[0335] The antisense oligomer of the present disclosure can have a modified chemical backbone as described herein or known in the art. For example, the antisense oligomer may be a peptide nucleic acid (PNA), a locked nucleic acid, a phosphorodiamidate morpholino oligomer, a 2′-OMe phosphorothioate oligomer, or a combination thereof. In an embodiment, the antisense oligomer is a phosphorodiamidate morpholino oligomer. In another embodiment, the antisense oligomer is a peptide nucleic acid. In yet another embodiment, the antisense oligomer is a locked nucleic acid. In still another embodiment, the antisense oligomer is a 2′-OMe phosphorothioate oligomer. In still another embodiment, the antisense oligomer is a combination of any of the above oligonucleotides having a modified chemical backbone.

[0336] In some embodiments, the antisense oligomer is conjugated to, e.g., covalently attached to, a delivery moiety such as, for example, a cell-penetrating peptide, an antibody, a fragment of an antibody, or an antigen fragment of an antibody. In an embodiment, the antisense oligomer is conjugated to a cell-penetrating peptide. In another embodiment, the antisense oligomer is conjugated to a cell-penetrating peptide, wherein the cell-penetrating peptide is selected from rTAT, Tat, R9F2, R5F2R4, R4, R5, R6, R7, R8, R9, (RXR)4, (RXR)5, (RXRRBR)2, (RAR)4F2, (RGR)4F2, and RBRBYLIQFRBRRBR, wherein A represents alanine, B represents beta-alanine, F represents phenylalanine, G represents glycine, I represents isoleucine, L represents leucine, Q represents glutamine, R represents arginine, X represent 6-aminohexanoic acid, and Y represents tyrosine. In yet another embodiment, the antisense oligomer is conjugated to an antibody, an antibody fragment, or an antigen fragment of an antibody.

[0337] The antisense oligomer of the present disclosure may be attached to the delivery moiety via a linker. In an embodiment, the linker is a direct bond from the antisense oligomer to thedelivery moiety. In another embodiment, the linker is an amino acid such as, for example, a glycine amino acid, a proline amino acid, or a glutamic amino acid. In a particular embodiment, the linker is a glycine amino acid or a proline amino acid.

[0338] Provided herein is an antisense oligomer, or a pharmaceutically acceptable salt thereof, having a structure of Formula (I):(I), wherein A′, R1, R2, t, E′, and G are as described herein.

[0259] In certain embodiments, t is 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, or 28. In some embodiments, each R2taken together forms a targeting sequence of 13-30 bases. In some embodiments, each R2taken together forms a targeting sequence of 11-28 bases. In some embodiments, each R2taken together forms a targeting sequence of 18-27 bases. In some embodiments, each R2taken together forms a targeting sequence of 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, or 30 bases. In certain embodiments, the pharmaceutically acceptable salt is an HCl salt.

[0260] In an embodiment, E′ is selected from H, -C1-6-alkyl, -C(O)C1-6-alkyl, benzoyl, stearoyl, trityl, monomethoxytrityl, dimethoxytrityl, trimethoxytrityl, and.

[0339] In a further embodiment, E′ is selected from -H, -C(O)CH3, benzoyl, stearoyl, trityl, 4- methoxytrityl, and.

[0341] In an embodiment, at least one of the following is true:

[0342] In an embodiment, A′ is selected from:and E′ is.

[0343] In an embodiment, A′ is

[0344] E′ is selected from H, -C(O)CH3, trityl, 4-methoxytrityl, benzoyl, and stearoyl. In an embodiment, each R1is -N(CH3)2. In an embodiment, L is glycine, proline, or b-alanine. In an embodiment, L is glycine. In an embodiment, L is proline. In an embodiment, L is b-alanine. In certain embodiments, the pharmaceutically acceptable salt is an HCl salt.

[0345] In some embodiments, provided herein is an antisense oligomer, which is an oligomer of Formula (IA):or a pharmaceutically acceptable salt thereof, wherein: A′ is a moiety selected from:are as describedherein.

[0346] In certain embodiments, t is 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, or 28. In some embodiments, each R2taken together forms a targeting sequence of 13-30 bases. In some embodiments, each R2taken together forms a targeting sequence of 11-28 bases. In some embodiments, each R2taken together forms a targeting sequence of 18-27 bases. In some embodiments, each R2taken together forms a targeting sequence of 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, or 30 bases. In certain embodiments, the pharmaceutically acceptable salt is an HCl salt.

[0347] In some embodiments, provided herein is an antisense oligomer, which is an oligomer of Formula (II):or a pharmaceutically acceptable salt thereof, wherein t, G, and R2are as described herein.

[0348] In certain embodiments, t is 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, or 28. In some embodiments, each R2taken together forms a targeting sequence of 13-30 bases. In some embodiments, each R2taken together forms a targeting sequence of 11-28 bases. In some embodiments, each R2taken together forms a targeting sequence of 18-27 bases. In some embodiments, each R2taken together forms a targeting sequence of 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, or 30 bases. In certain embodiments, the pharmaceutically acceptable salt is an HCl salt.

[0349] In some embodiments, provided herein is an antisense oligomer, which is an oligomer of Formula (III):or a pharmaceutically acceptable salt thereof, wherein n is 11-28 and R2is as described herein.

[0350] In certain embodiments, n is 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, or 28. In some embodiments, each R2taken together forms a targeting sequence of 13- 30 bases. In some embodiments, each R2taken together forms a targeting sequence of 11-28 bases. In some embodiments, each R2taken together forms a targeting sequence of 18-27 bases. In some embodiments, each R2taken together forms a targeting sequence of 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, or 30 bases. In certain embodiments, the pharmaceutically acceptable salt is an HCl salt.

[0351] In some embodiments, provided herein is an antisense oligomer, which is an oligomer of Formula (IV):(IV), wherein n is 11-28 and R2is as described herein.

[0352] In certain embodiments, n is 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, or 28. In some embodiments, each R2taken together forms a targeting sequence of 13-30 bases. In some embodiments, each R2taken together forms a targeting sequence of 11-28 bases. In some embodiments, each R2taken together forms a targeting sequence of 18-27 bases. In some embodiments, each R2taken together forms a targeting sequence of 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, or 30 bases.

[0353] In an embodiment, J is selected from rTAT, TAT, R9F2, R5F2R4, R4, R5, R6, R7, R8, R9, (RXR)4, (RXR)5, (RXRRBR)2, (RAR)4F2, (RGR)4F2, and RBRBYLIQFRBRRBR, wherein A represents alanine, B represents βbeta-alanine, F represents phenylalanine, G represents glycine, R represents arginine, and X represent 6-aminohexanoic acid.

[0354] In an embodiment, G is selected from H, C(O)CH3, benzoyl, and stearoyl. In an embodiment, G is H or -C(O)CH3. In an embodiment, G is H. In an embodiment, G is -C(O)CH3.

[0355] In certain embodiments, the antisense oligomer is selected from:,Ĭ

[0356] In certain embodiments, the antisense oligomer has the structure:.

[0357] In certain embodiments, the antisense oligomer has the structure:.

[0358] In certain embodiments, the antisense oligomer has the structure:.

[0359] In certain embodiments, the antisense oligomer has the structure:.

[0360] In certain embodiments, the antisense oligomer has the structure:

[0361] In certain embodiments, the antisense oligomer has the structure:.

[0362] Provided herein is a pharmaceutical composition, comprising: an antisense oligomer, or a pharmaceutically acceptable salt thereof, of Formulae (I), (IA), (II), (III), (IV) and / or (V); and at least one pharmaceutically acceptable carrier.

[0363] Provided herein is a method of treating a disease in a subject in need thereof, the method comprising administering a therapeutically effective amount of an antisense oligomer, including an oligomer of Formulae (I), (IA), (II), (III), (IV), and / or (V), or a pharmaceutical composition disclosed herein to the subject.

[0364] In an embodiment, the disease is associated with aberrant expression of dynamin 2 (DNM2) protein. In certain embodiments, the disease is a centronuclear myopathy (CNM). In one embodiment, the subject is a human.III. Oligomer Chemistry Features

[0365] Also provided herein are antisense oligomers useful for targeting the human DNM2 gene pre-mRNA, wherein the antisense oligomer is a modified antisense oligomer. Examples of modified antisense oligomers include, without limitation, morpholino oligomers, phosphorothioate modified oligomers, 2′-O-methyl modified oligomers, peptide nucleic acid (PNA), locked nucleic acid (LNA), phosphorothioate oligomers, 2′-O-MOE modified oligomers, 2′-fluoro-modified oligomer, 2′-O,4′-C-ethylene-bridged nucleic acids (ENAs), tricyclo-DNAs, tricyclo-DNA phosphorothioate subunits, 2′-O-[2-(N- methylcarbamoyl)ethyl] modified oligomers, including combinations of any of the foregoing. Phosphorothioate and 2′-O-Me-modified chemistries can be combined to generate a 2′-O-Me-phosphorothioate backbone. See, e.g., PCT Publication Nos. WO / 2013 / 112053 and WO / 2009 / 008725, which are hereby incorporated by reference in their entireties.

[0366] In some embodiments, the nucleobases of the modified antisense oligomer are linked to morpholino ring structures, wherein the morpholino ring structures are joined by phosphoros- containing intersubunit linkages joining a morpholino nitrogen of one ring structure to a 5′ exocyclic carbon of an adjacent ring structure.

[0367] In some embodiments, the nucleobases of the antisense oligomer are linked to a peptide nucleic acid (PNA), wherein the phosphate-sugar polynucleotide backbone is replaced by a flexible pseudo-peptide polymer to which the nucleobases are linked. In some aspects, at least one of the nucleobases of the antisense oligomer is linked to a locked nucleic acid (LNA), wherein the locked nucleic acid structure is a nucleotide analog that is chemically modified where the ribose moiety has an extra bridge connecting the 2′ oxygen and the 4′ carbon.

[0368] In some embodiments, at least one of the nucleobases of the antisense oligomer is linked to a bridged nucleic acid (BNA), wherein the sugar conformation is restricted or locked by the introduction of an additional bridged structure to the furanose skeleton. In some aspects, at least one of the nucleobases of the antisense oligomer is linked to a 2′-O,4′-C-ethylene- bridged nucleic acid (ENA).

[0369] In some embodiments, the modified antisense oligomer may contain unlocked nucleic acid (UNA) subunits. UNAs and UNA oligomers are an analogue of RNA in which the C2′-C3′ bond of the subunit has been cleaved.

[0370] In some embodiments, the modified antisense oligomer contains one or more phosphorothioates (or S-oligos), in which one of the nonbridging oxygens is replaced by sulfur. In some aspects, the modified antisense oligomer contains one or more 2′ O-Methyl, 2′ O-MOE, MCE, and 2′-F in which the 2′-OH of the ribose is substituted with a methyl, methoxy ethyl, 2-(N- methylcarbamoyl)ethyl, or fluoro group, respectively.

[0371] In some embodiments, the modified antisense oligomer is a tricyclo-DNA (tc-DNA) which is a constrained DNA analog in which each nucleotide is modified by the introduction of a cyclopropane ring to restrict conformational flexibility of the backbone and to optimize the backbone geometry of the torsion angle g.

[0372] In some embodiments, at least one of the nucleobases of the antisense oligomer is linked to a bridged nucleic acid (BNA), wherein the sugar conformation is restricted or locked by the introduction of an additional bridged structure to the furanose skeleton. In some aspects, at least one of the nucleobases of the antisense oligomer is linked to a 2′-O,4′-C-ethylene- bridged nucleic acid (ENA). In such aspects, each nucleobase which is linked to a BNA or ENA comprises a 5-methyl group. Exemplary embodiments of oligomer chemistries of the disclosure are further described below. 1. Peptide Nucleic Acids (PNAs)

[0373] Peptide nucleic acids (PNAs) are analogs of DNA in which the backbone is structurally homomorphous with a deoxyribose backbone, consisting of N-(2-aminoethyl) glycine units to which pyrimidine or purine bases are attached. PNAs containing natural pyrimidine and purine bases hybridize to complementary oligomers obeying Watson-Crick base-pairing rules, and mimic DNA in terms of base-pair recognition. The backbone of PNAs is formed by peptide bonds rather than phosphodiester bonds, making them well-suited for antisense applications (see structure below). The backbone is uncharged, resulting in PNA / DNA or PNA / RNA duplexes that exhibit greater than normal thermal stability. PNAs are not recognized by nucleases or proteases. A non-limiting example of a PNA is depicted below.

[0374] Despite a radical structural change to the natural structure, PNAs are capable of sequence-specific binding in a helix form to DNA or RNA. Characteristics of PNAs include a high binding affinity to complementary DNA or RNA, a destabilizing effect caused by single-base mismatch, resistance to nucleases and proteases, hybridization with DNA or RNA independentof salt concentration, and triplex formation with homopurine DNA. PANAGENE™ has developed its proprietary Bts PNA monomers (Bts; benzothiazole-2-sulfonyl group) and proprietary oligomerization process. The PNA oligomerization using Bts PNA monomers is composed of repetitive cycles of deprotection, coupling, and capping. PNAs can be produced synthetically using any technique known in the art. See, e.g., U.S. Pat. Nos.: 6,969,766; 7,211,668; 7,022,851; 7,125,994; 7,145,006; and 7,179,896. See also U.S. Pat. Nos.: 5,539,082; 5,714,331; and 5,719,262 for the preparation of PNAs. Further teaching of PNA compounds can be found in Nielsen et al., Science, 254:1497-1500, 1991. Each of the foregoing is incorporated by reference in its entirety. 2. Locked Nucleic Acids (LNAs)

[0375] Antisense oligomers may also contain "locked nucleic acid" subunits (LNAs). "LNAs" are a member of a class of modifications called bridged nucleic acid (BNA). BNA is characterized by a covalent linkage that locks the conformation of the ribose ring in a C30-endo (northern) sugar pucker. For LNA, the bridge is composed of a methylene between the 2′-O and the 4′-C positions. LNA enhances backbone preorganization and base stacking to increase hybridization and thermal stability.

[0376] The structures of LNAs can be found, for example, in Wengel, et al., Chemical Communications (1998) 455; Koshkin et al., Tetrahedron (1998) 54:3607; Jesper Wengel, Accounts of Chem. Research (1999) 32:301; Obika, et al., Tetrahedron Letters (1997) 38:8735; Obika, et al., Tetrahedron Letters (1998) 39:5401; and Obika, et al., Bioorganic Medicinal Chemistry (2008) 16:9230, which are hereby incorporated by reference in their entirety. A non- limiting example of an LNA is depicted below.

[0377] Antisense oligomers of the disclosure may incorporate one or more LNAs; in some cases, the antisense oligomers may be entirely composed of LNAs. Methods for the synthesis ofindividual LNA nucleoside subunits and their incorporation into oligomers are described, for example, in U.S. Pat.: Nos.7,572,582; 7,569,575; 7,084,125; 7,060,809; 7,053,207; 7,034,133; 6,794,499; and 6,670,461; each of which is incorporated by reference in its entirety. Typical intersubunit linkers include phosphodiester and phosphorothioate moieties; alternatively, non- phosphorous-containing linkers may be employed. Further embodiments include an LNA containing antisense oligomer where each LNA subunit is separated by a DNA subunit. Certain antisense oligomers are composed of alternating LNA and DNA subunits where the intersubunit linker is phosphorothioate. 3. Ethylene-Bridged Nucleic Acids (ENAs)

[0378] 2′-O,4′C-ethylene-bridged nucleic acids (ENAs) are another member of the class of BNAs. A non-limiting example is depicted below.

[0379] ENA oligomers and their preparation are described in Obika et al., Tetrahedron Lett (1997) 38 (50): 8735, which is hereby incorporated by reference in its entirety. Antisense oligomers of the disclosure may incorporate one or more ENA subunits. 4. Unlocked nucleic acid (UNA)

[0380] Antisense oligomers may also contain unlocked nucleic acid (UNA) subunits. UNAs and UNA oligomers are an analog of RNA in which the C2′-C3′ bond of the subunit has been cleaved. Whereas LNA is conformationally restricted (relative to DNA and RNA), UNA is very flexible. UNAs are disclosed, for example, in WO 2016 / 070166. A non-limiting example of an UNA is depicted below.

[0381] Typical intersubunit linkers include phosphodiester and phosphorothioate moieties; alternatively, non-phosphorous containing linkers may be employed. 5. Phosphorothioates

[0382] "Phosphorothioates" (or S-oligos) are a variant of normal DNA in which one of the nonbridging oxygens is replaced by sulfur. A non-limiting example of a phosphorothioate is depicted below.

[0383] The sulfurization of the internucleotide bond reduces the action of endo-and exonucleases including 5′ to 3′ and 3′ to 5′ DNA POL 1 exonuclease, nucleases S1 and P1, RNases, serum nucleases, and snake venom phosphodiesterase. Phosphorothioates are made by two principal routes: by the action of a solution of elemental sulfur in carbon disulfide on a hydrogen phosphonate, or by the method of sulfurizing phosphite triesters with either tetraethylthiuram disulfide (TETD) or 3H-1, 2-benzodithiol-3-one 1, 1-dioxide (BDTD) (see, e.g., Iyer et al., J. Org. Chem.55, 4693-4699, 1990, which is hereby incorporated by reference in its entirety). The latter methods avoid the problem of elemental sulfur's insolubility in most organic solvents and the toxicity of carbon disulfide. The TETD and BDTD methods also yield higher purity phosphorothioates. 6. Tricyclo-DNAs and Tricyclo-Phosphorothioate Subunits

[0384] Tricyclo-DNAs (tc-DNA) are a class of constrained DNA analogs in which each nucleotide is modified by the introduction of a cyclopropane ring to restrict conformational flexibility of the backbone and to optimize the backbone geometry of the torsion angle γ. Homobasic adenine- and thymine-containing tc-DNAs form extraordinarily stable A-T base pairs with complementary RNAs. Tricyclo-DNAs and their synthesis are described in International Patent Application Publication No. WO 2010 / 115993, which is hereby incorporated by reference in its entirety. Antisense oligomers of the disclosure may incorporate one or more tricycle-DNAsubunits; in some cases, the antisense oligomers may be entirely composed of tricycle-DNA subunits.

[0385] Tricyclo-phosphorothioate subunits are tricyclo-DNA subunits with phosphorothioate intersubunit linkages. Tricyclo-phosphorothioate subunits and their synthesis are described in International Patent Application Publication No. WO 2013 / 053928, which is hereby incorporated by reference in its entirety. Antisense oligomers of the disclosure may incorporate one or more tricycle-DNA subunits; in some cases, the antisense oligomers may be entirely composed of tricycle-DNA subunits. A non-limiting example of a tricycle-DNA / tricycle- phosphorothioate subunit is depicted below.7. 2′-O-Methyl, 2′-O-MOE, and 2′-F Oligomers

[0386] "2′-O-Me oligomer" molecules carry a methyl group at the 2′-OH residue of the ribose molecule.2′-O-Me-RNAs show the same (or similar) behavior as DNA but are protected against nuclease degradation.2′-O-Me-RNAs can also be combined with phosphorothioate oligomers (PTOs) for further stabilization.2′O-Me oligomers (phosphodiester or phosphorothioate) can be synthesized according to routine techniques in the art (see, e.g., Yoo et al., Nucleic Acids Res. 32:2008-16, 2004, which is hereby incorporated by reference in its entirety). A non-limiting example of a 2′-O-Me oligomer is depicted below.2′-O-Me

[0387] 2′-O-Methoxyethyl Oligomers (2′-O-MOE) carry a methoxyethyl group at the 2′-OH residue of the ribose molecule and are discussed in Martin et al., Helv. Chim. Acta, 78, 486-504,1995, which is hereby incorporated by reference in its entirety. A non-limiting example of a 2′-O- MOE subunit is depicted below.

[0388] 2′-Fluoro (2′-F) oligomers have a fluoro radical in at the 2′ position in place of the 2′-OH. A non-limiting example of a 2′-F oligomer is depicted below.

[0389] 2′-fluoro oligomers are further described in WO 2004 / 043977, which is hereby incorporated by reference in its entirety.

[0390] 2′-O-Methyl, 2′-O-MOE, and 2′-F oligomers may also comprise one or more phosphorothioate (PS) linkages as depicted below.2′-O-Methyl PS 2′-O-MOE PS 2′-F PS

[0391] Additionally, 2′-O-Methyl, 2′-O-MOE, and 2′-F oligomers may comprise PS intersubunit linkages throughout the oligomer, for example, as in the 2′-O-methyl PS oligomer drisapersen depicted below.

[0392] Alternatively, 2′-O-Methyl, 2′-O-MOE, and / or 2′-F oligomers may comprise PS linkages at the ends of the oligomer, as depicted below:wherein: R is CH2CH2OCH3(methoxyethyl or MOE); and X, Y, and Z denote the number of nucleotides contained within each of the designated 5′-wing, central gap, and 3′-wing regions, respectively.

[0393] Antisense oligomers of the disclosure may incorporate one or more 2′-O-methyl, 2′-O- MOE, and 2′-F subunits and may utilize any of the intersubunit linkages described here. In some instances, an antisense oligomer of the disclosure may be composed of entirely 2′-O-methyl, 2′- O-MOE, or 2′-F subunits. One embodiment of the antisense oligomers of the disclosure is composed entirely of 2′-O-methyl subunits. 8. 2′-O-[2-(N-methylcarbamoyl)ethyl] Oligomers (MCEs)

[0394] MCEs are another example of 2′-O modified ribonucleosides useful in the antisense oligomers of the disclosure. Here, the 2′-OH is derivatized to a 2-(N-methylcarbamoyl)ethyl moiety to increase nuclease resistance. A non-limiting example of an MCE oligomer is depicted below.

[0395] MCEs and their synthesis are described in Yamada et al., J. Org. Chem. (2011) 76(9):3042-53, which is hereby incorporated by reference in its entirety. Antisense oligomers of the disclosure may incorporate one or more MCE subunits. 9. Stereo-Specific Oligomers

[0396] Stereo-specific oligomers are those in which the stereo chemistry of each phosphorous- containing linkage is fixed by the method of synthesis such that a substantially stereo-pure oligomer is produced. A non-limiting example of a stereo-specific oligomer is depicted below.

[0397] In the above example, each phosphorous of the oligomer has the same stereo configuration. Additional examples include the oligomers described herein. For example, LNAs, ENAs, Tricyclo-DNAs, MCEs, 2′-O-Methyl, 2′-O-MOE, 2′-F, and morpholino-based oligomers can be prepared with stereo-specific phosphorous-containing internucleoside linkages such as, for example, phosphorothioate, phosphodiester, phosphoramidate, phosphorodiamidate, orother phosphorous-containing internucleoside linkages. Stereo specific oligomers, methods of preparation, chiral controlled synthesis, chiral design, and chiral auxiliaries for use in the preparation of such oligomers are detailed, for example, in WO2017192664, WO2017192679, WO2017062862, WO2017015575, WO2017015555, WO2015107425, WO2015108048, WO2015108046, WO2015108047, WO2012039448, WO2010064146, WO2011034072, WO2014010250, WO2014012081, WO20130127858, and WO2011005761, each of which is hereby incorporated by reference in its entirety.

[0398] Stereo-specific oligomers can have phosphorous-containing internucleoside linkages in an RPor SPconfiguration. Chiral phosphorous-containing linkages in which the stereo configuration of the linkages is controlled is referred to as "stereopure," while chiral phosphorous-containing linkages in which the stereo configuration of the linkages is uncontrolled is referred to as "stereorandom." In certain embodiments, the oligomers of the disclosure comprise a plurality of stereopure and stereorandom linkages, such that the resulting oligomer has stereopure subunits at pre-specified positions of the oligomer. An example of the location of the stereopure subunits is provided in international patent application publication number WO 2017 / 062862 A2 in Figures 7A and 7B. In an embodiment, all the chiral phosphorous-containing linkages in an oligomer are stereorandom. In an embodiment, all the chiral phosphorous-containing linkages in an oligomer are stereopure.

[0399] In an embodiment of an oligomer with n chiral phosphorous-containing linkages (where n is an integer of 1 or greater), all n of the chiral phosphorous-containing linkages in the oligomer are stereorandom. In an embodiment of an oligomer with n chiral phosphorous-containing linkages (where n is an integer of 1 or greater), all n of the chiral phosphorous-containing linkages in the oligomer are stereopure. In an embodiment of an oligomer with n chiral phosphorous-containing linkages (where n is an integer of 1 or greater), at least 10% (to the nearest integer) of the n phosphorous-containing linkages in the oligomer are stereopure. In an embodiment of an oligomer with n chiral phosphorous-containing linkages (where n is an integer of 1 or greater), at least 20% (to the nearest integer) of the n phosphorous-containing linkages in the oligomer are stereopure. In an embodiment of an oligomer with n chiral phosphorous- containing linkages (where n is an integer of 1 or greater), at least 30% (to the nearest integer) of the n phosphorous-containing linkages in the oligomer are stereopure. In an embodiment of an oligomer with n chiral phosphorous-containing linkages (where n is an integer of 1 or greater), at least 40% (to the nearest integer) of the n phosphorous-containing linkages in the oligomer are stereopure. In an embodiment of an oligomer with n chiral phosphorous-containing linkages (where n is an integer of 1 or greater), at least 50% (to the nearest integer) of the n phosphorous-containing linkages in the oligomer are stereopure. In an embodiment of anoligomer with n chiral phosphorous-containing linkages (where n is an integer of 1 or greater), at least 60% (to the nearest integer) of the n phosphorous-containing linkages in the oligomer are stereopure. In an embodiment of an oligomer with n chiral phosphorous-containing linkages (where n is an integer of 1 or greater), at least 70% (to the nearest integer) of the n phosphorous-containing linkages in the oligomer are stereopure. In an embodiment of an oligomer with n chiral phosphorous-containing linkages (where n is an integer of 1 or greater), at least 80% (to the nearest integer) of the n phosphorous-containing linkages in the oligomer are stereopure. In an embodiment of an oligomer with n chiral phosphorous-containing linkages (where n is an integer of 1 or greater), at least 90% (to the nearest integer) of the n phosphorous-containing linkages in the oligomer are stereopure.

[0400] In an embodiment of an oligomer with n chiral phosphorous-containing linkages (where n is an integer of 1 or greater), the oligomer contains at least 2 contiguous stereopure phosphorous-containing linkages of the same stereo orientation (i.e., either SPor RP). In an embodiment of an oligomer with n chiral phosphorous-containing linkages (where n is an integer of 1 or greater), the oligomer contains at least 3 contiguous stereopure phosphorous-containing linkages of the same stereo orientation (i.e., either SPor RP). In an embodiment of an oligomer with n chiral phosphorous-containing linkages (where n is an integer of 1 or greater), the oligomer contains at least 4 contiguous stereopure phosphorous-containing linkages of the same stereo orientation (i.e., either SPor RP). In an embodiment of an oligomer with n chiral phosphorous-containing linkages (where n is an integer of 1 or greater), the oligomer contains at least 5 contiguous stereopure phosphorous-containing linkages of the same stereo orientation (i.e., either SPor RP). In an embodiment of an oligomer with n chiral phosphorous-containing linkages (where n is an integer of 1 or greater), the oligomer contains at least 6 contiguous stereopure phosphorous-containing linkages of the same stereo orientation (i.e., either SP or RP). In an embodiment of an oligomer with n chiral phosphorous-containing linkages (where n is an integer of 1 or greater), the oligomer contains at least 7 contiguous stereopure phosphorous- containing linkages of the same stereo orientation (i.e., either SP or RP). In an embodiment of an oligomer with n chiral phosphorous-containing linkages (where n is an integer of 1 or greater), the oligomer contains at least 8 contiguous stereopure phosphorous-containing linkages of the same stereo orientation (i.e., either SP or RP). In an embodiment of an oligomer with n chiral phosphorous-containing linkages (where n is an integer of 1 or greater), the oligomer contains at least 9 contiguous stereopure phosphorous-containing linkages of the same stereo orientation (i.e., either SP or RP). In an embodiment of an oligomer with n chiral phosphorous-containing linkages (where n is an integer of 1 or greater), the oligomer contains at least 10 contiguous stereopure phosphorous-containing linkages of the same stereo orientation (i.e., either SP orRP). In an embodiment of an oligomer with n chiral phosphorous-containing linkages (where n is an integer of 1 or greater), the oligomer contains at least 11 contiguous stereopure phosphorous-containing linkages of the same stereo orientation (i.e., either SPor RP). In an embodiment of an oligomer with n chiral phosphorous-containing linkages (where n is an integer of 1 or greater), the oligomer contains at least 12 contiguous stereopure phosphorous- containing linkages of the same stereo orientation (i.e., either SPor RP). In an embodiment of an oligomer with n chiral phosphorous-containing linkages (where n is an integer of 1 or greater), the oligomer contains at least 13 contiguous stereopure phosphorous-containing linkages of the same stereo orientation (i.e., either SPor RP). In an embodiment of an oligomer with n chiral phosphorous-containing linkages (where n is an integer of 1 or greater), the oligomer contains at least 14 contiguous stereopure phosphorous-containing linkages of the same stereo orientation (i.e., either SPor RP). In an embodiment of an oligomer with n chiral phosphorous-containing linkages (where n is an integer of 1 or greater), the oligomer contains at least 15 contiguous stereopure phosphorous-containing linkages of the same stereo orientation (i.e., either SPor RP). In an embodiment of an oligomer with n chiral phosphorous-containing linkages (where n is an integer of 1 or greater), the oligomer contains at least 16 contiguous stereopure phosphorous-containing linkages of the same stereo orientation (i.e., either SPor RP). In an embodiment of an oligomer with n chiral phosphorous-containing linkages (where n is an integer of 1 or greater), the oligomer contains at least 17 contiguous stereopure phosphorous- containing linkages of the same stereo orientation (i.e., either SPor RP). In an embodiment of an oligomer with n chiral phosphorous-containing linkages (where n is an integer of 1 or greater), the oligomer contains at least 18 contiguous stereopure phosphorous-containing linkages of the same stereo orientation (i.e., either SPor RP). In an embodiment of an oligomer with n chiral phosphorous-containing linkages (where n is an integer of 1 or greater), the oligomer contains at least 19 contiguous stereopure phosphorous-containing linkages of the same stereo orientation (i.e., either SP or RP). In an embodiment of an oligomer with n chiral phosphorous-containing linkages (where n is an integer of 1 or greater), the oligomer contains at least 20 contiguous stereopure phosphorous-containing linkages of the same stereo orientation (i.e., either SP or RP).

[0401] In an embodiment of an oligomer with n chiral phosphorous-containing linkages (where n is an integer of 1 or greater), the oligomer contains at least 2 contiguous stereopure phosphorous-containing linkages of the same stereo orientation (i.e., either SP or RP) and at least 2 contiguous stereopure phosphorous-containing linkages of the other stereo orientation. For example, the oligomer can contain at least 2 contiguous stereopure phosphorous-containinglinkages of the SP orientation and at least 2 contiguous stereopure phosphorous-containing linkages of the RPorientation.

[0402] In an embodiment of an oligomer with n chiral phosphorous-containing linkages (where n is an integer of 1 or greater), the oligomer contains at least 2 contiguous stereopure phosphorous-containing linkages of the same stereo orientation in an alternating pattern. For example, the oligomer can contain the following in order: 2 or more RP,2 or more SP, and 2 or more RP, etc. 10. Morpholino Oligomers

[0403] Exemplary embodiments of the disclosure relate to phosphorodiamidate morpholino oligomers of the following general structure:and as described in Figure 2 of Summerton, J., et al., Antisense & Nucleic Acid Drug Development, 7: 187-195 (1997). Morpholinos as described herein are intended to cover all stereoisomers and tautomers of the foregoing general structure. The synthesis, structures, and binding characteristics of morpholino oligomers are detailed in U.S. Patent Nos.: 5,698,685; 5,217,866; 5,142,047; 5,034,506; 5,166,315; 5,521,063; 5,506,337; 8,076,476; and 8,299,206, all of which are incorporated herein by reference.

[0404] In certain embodiments, a morpholino is conjugated at the 5′ or 3′ end of the oligomer with a "tail" moiety to increase its stability and / or solubility. Exemplary tails include:

[0405] In various aspects, the disclosure provides antisense oligomers according to Formulae (I), (IA), (II), (III), (IV), and / or (V), and pharmaceutically acceptable salts thereof.

[0406] In an embodiment, the antisense oligomers disclosed herein, including antisense oligomers of Formulae (I), (IA), (II), (III), (IV), and / or (V), comprise a targeting sequence complementary to a target region within a pre-mRNA of the human DNM2 gene represented by SEQ ID NO: 1.

[0407] In some embodiments of the antisense oligomers disclosed herein, including antisense oligomers of Formula (I), Formula (IA), Formula (II), Formula (III), Formula (IV), and / or Formula(V), the target region is within an exon internal region of the human DNM2 gene pre-mRNA selected from exon 2 (SEQ ID NO: 2), exon 6 (SEQ ID NO: 3), exon 7 (SEQ ID NO: 4), exon 8 (SEQ ID NO: 5), exon 9 (SEQ ID NO: 6), exon 12 (SEQ ID NO: 7), exon 13 (SEQ ID NO: 8), exon 16 (SEQ ID NO: 9), and exon 19 (SEQ ID NO: 10).

[0408] In some embodiments of the antisense oligomers disclosed herein, including antisense oligomers of Formula (I), Formula (IA), Formula (II), Formula (III), and Formula (IV), the target region is within an exon internal region of the human DNM2 gene pre-mRNA selected from exon 2 (SEQ ID NO: 2), exon 9 (SEQ ID NO: 6), exon 12 (SEQ ID NO: 7), and exon 13 (SEQ ID NO: 8).

[0409] In some embodiments of the antisense oligomers disclosed herein, including antisense oligomers of Formula (I), Formula (IA), Formula (II), Formula (III), Formula (IV), and / or Formula (V), the target region is within an intron-exon junction or an exon-intron junction region of the human DNM2 gene pre-mRNA selected from intron 1 / exon 2 junction, exon 2 / intron 2 junction, intron 5 / exon 6 junction, exon 6 / intron 6 junction, intron 6 / exon 7 junction, exon 7 / intron 7 junction, intron 7 / exon 8 junction, exon 8 / intron 8 junction, intron 8 / exon 9 junction, exon 9 / intron 9 junction, intron 11 / exon 12 junction, exon 12 / intron 12 junction, intron 12 / exon 13 junction, exon 13 / intron 13 junction, intron 15 / exon 16 junction, exon 16 / intron 16 junction, intron 18 / exon 19 junction, and exon 19 / intron 19 junction.

[0410] In some embodiments of the antisense oligomers disclosed herein, including antisense oligomers of Formula (I), Formula (IA), Formula (II), Formula (III), Formula (IV), and / or Formula (V), the target region is within an intron-exon junction or an exon-intron junction of the human DNM2 gene pre-mRNA selected from intron 1 / exon 2 junction, exon 2 / intron 2 junction, intron 8 / exon 9 junction, exon 9 / intron 9 junction, intron 11 / exon 12 junction, exon 12 / intron 12 junction, intron 12 / exon 13 junction, and exon 13 / intron 13 junction.

[0411] In some embodiments of the antisense oligomers disclosed herein, including antisense oligomers of Formula (I), Formula (IA), Formula (II), Formula (III), Formula (IV), and / or Formula (V), the target region is within an intron internal region of the human DNM2 gene pre-mRNA selected from intron 2 (SEQ ID NO: 11) and intron 12 (SEQ ID NO: 12).

[0412] In certain embodiments, the target region of the human DNM2 gene pre-mRNA is DNM2 H2A (-10+15), DNM2 H2A(-7+17), DNM2 H2A(+3+27), DNM2 H2A(+15+37), DNM2 H2A(+21+45), DNM2 H2A(+23+47), DNM2 H2A(+27+51), DNM2 H2A(+37+61), DNM2 H2A(+46+70), DNM2 H2A (+48+72), DNM2 H2D(+20-5), DNM2 H2D (+13-12), DNM2 H2D(+12- 13), DNM2 H2D(+11-14), DNM2 H2D(+10-15), DNM2 H2D(+9-16), DNM2 H2D(+8-17), DNM2 H2D(+7-18), DNM2 H2D(+6-19), DNM2 H2D(+5-20), DNM2 H2D(+4-21), DNM2 H2D(+3-22), DNM2 H2D(+2-23), DNM2 H2D(+1-24), DNM2 H2D(-1-25), DNM2 H2D(-2-26), DNM2 H2D(-3-27), DNM2 H2D(-4-28), DNM2 H2D(-5-29), DNM2 H2D(-6-30), DNM2 H9A(-12+13), DNM2 H9A(-5+20), DNM2 H9A(+1+25),DNM2 H9A(+6+30), DNM2 H9A(+16+40), DNM2 H9A(+25+49), DNM2 H9A(+36+60), DNM2 H9A(+37+61), DNM2 H9A(+42+66), DNM2 H9A(+43+62), DNM2 H9A(+43+63), DNM2 H9A(+43+64), DNM2 H9A(+43+65), DNM2 H9A(+43+66), DNM2 H9A(+43+67), DNM2 H9A(+44+67), DNM2 H9A(+44+68), DNM2 H9A(+45+67), DNM2 H9A (+46+67), DNM2 H9A(+47+67), DNM2 H9A(+48+67), DNM2 H9D(+24-1), DNM2 H9D(+23-2), DNM2 H9D(+22-3), DNM2 H9D(+21-4), DNM2 H9D(+20-5), DNM2 H9D(+19-6), DNM2 H9D (+18-7), DNM2 H9D(+17-8), DNM2 H9D(+16-9), DNM2 H9D(+15-10), DNM2 H9D(+14-11), DNM2 H9D(+13-12), DNM2 H9D(+12-13), DNM2 H9D(+11- 14), DNM2 H9D(+10-15), DNM2 H9D(+9-16), DNM2 H9D(+8-12), DNM2 H9D(+8-13), DNM2 H9D(+8-14), DNM2 H9D(+8-15), DNM2 H9D(+8-17), DNM2 H9D(+7-18), DNM2 H9D(+7-17), DNM2 H9D(+6-19), DNM2 H9D(+6-17), DNM2 H9D(+5-17), DNM2 H9D(+5-20), DNM2 H9D(+4- 17), DNM2 H9D(+4-21), DNM2 H9D(+3-17), DNM2 H9D(+3-22), DNM2 H12A(-13+12), DNM2 H12A(-3+22), DNM2 H12A(+4+28), DNM2 H12A(+7+31), DNM2 H12A(+10+34), DNM2 H12A(+11+35), DNM2 H12A(+12+36), DNM2 H12A(+13+37), DNM2 H12A(+14+38), DNM2 H12A(+15+39), DNM2 H12A(+16+40), DNM2 H12A(+17+41), DNM2 H12A(+18+42), DNM2 H12A(+19+43), DNM2 H12A(+20+44), DNM2 H12A(+25+44), DNM2 H12A(+25+45), DNM2 H12A(+25+46), DNM2 H12A(+25+47), DNM2 H12A(+25+48), DNM2 H12A(+25+49), DNM2 H12A(+26+49), DNM2 H12A(+27+49), DNM2 H12A(+28+49), DNM2 H12A(+29+49), DNM2 H12A(+29+53), DNM2 H12A(+30+49), DNM2 H12A(+30+54), DNM2 H12A(+36+60), DNM2 H12A(+37+61), DNM2 H12A(+43+67), DNM2 H12D(+22-3), DNM2 H12D(+20-5), DNM2 H12D(+15-10), DNM2 H12A(+4+28), DNM2 H12A(+7+31), DNM2 H12A(+10+34), DNM2 H12A(+11+35), DNM2 H12A(+12+36), DNM2 H12A(+13+37), DNM2 H12A(+14+38), DNM2 H12A(+15+39), DNM2 H12A(+16+40), DNM2 H12A(+17+41), DNM2 H12A(+18+42), DNM2 H12A(+19+43), DNM2 H12A(+20+44), DNM2 H12A(+25+44), DNM2 H12A(+25+45), DNM2 H12A(+25+46), DNM2 H12A(+25+47), DNM2 H12A(+25+48), DNM2 H12A(+25+49), DNM2 H12A(+26+49), DNM2 H12A(+27+49), DNM2 H12A(+28+49), DNM2 H12A(+29+49), DNM2 H12A(+29+53), DNM2 H12A(+30+49), DNM2 H12A(+30+54), DNM2 H12A(+36+60), DNM2 H12A(+37+61), DNM2 H12A(+43+67), DNM2 H13A(-27-3), DNM2 H13A(-26-2), DNM2 H13A(- 25-1), DNM2 H13A(-24+1), DNM2 H13A(-23+2), DNM2 H13A(-22+3), DNM2 H13A(-21+4), DNM2 H13A(-20+5), DNM2 H13A(-19+6), DNM2 H13A(-18+7), DNM2 H13A(-17+8), DNM2 H13A(-16+9), DNM2 H13A(-15+10), DNM2 H13A(-14+11), DNM2 H13A(-13+12), DNM2 H13A(- 11+14), DNM2 H13A(-10+15), DNM2 H13A(-9+16), DNM2 H13A(-8+17), DNM2 H13A(-7+18), DNM2 H13A(-6+19), DNM2 H13A(-5+20), DNM2 H13A(-4+21), DNM2 H13A(-3+22), DNM2 H13A(-2+23), DNM2 H13A(-1+24), DNM2 H13A(+1+25), DNM2 H13A(+2+25), DNM2H13A(+3+27), DNM2 H13A(+4+23), DNM2 H13A(+4+24), DNM2 H13A(+4+25), DNM2 H13A(+4+26), DNM2 H13A(+4+27), DNM2 H13A(+4+28), DNM2 H13A(+5+28), DNM2 H13A(+6+28), DNM2 H13A(+6+30), DNM2 H13A(+7+28), DNM2 H13A(+8+28), DNM2 H13A(+9+28), DNM2 H13A(+16+40), DNM2 H13D(+22-3), or DNM2 H13D(+7-18).

[0413] In certain embodiments, the target region is DNM2 H2A (-10+15). In certain embodiments, the target region is DNM2 H2A(-7+17). In certain embodiments, the target region is DNM2 H2A(+3+27). In certain embodiments, the target region is DNM2 H2A(+15+37). In certain embodiments, the target region is DNM2 H2A(+21+45). In certain embodiments, the target region is DNM2 H2A(+23+47). In certain embodiments, the target region is DNM2 H2A(+27+51). In certain embodiments, the target region is DNM2 H2A(+37+61). In certain embodiments, the target region is DNM2 H2A(+46+70). In certain embodiments, the target region is DNM2 H2A (+48+72). In certain embodiments, the target region is DNM2 H2D(+20-5). In certain embodiments, the target region is DNM2 H2D (+13-12). In certain embodiments, the target region is DNM2 H2D(+12-13). In certain embodiments, the target region is DNM2 H2D(+11-14). In certain embodiments, the target region is DNM2 H2D(+10-15). In certain embodiments, the target region is DNM2 H2D(+9-16). In certain embodiments, the target region is DNM2 H2D(+8-17). In certain embodiments, the target region is DNM2 H2D(+7-18). In certain embodiments, the target region is DNM2 H2D(+6-19). In certain embodiments, the target region is DNM2 H2D(+5-20). In certain embodiments, the target region is DNM2 H2D(+4-21). In certain embodiments, the target region is DNM2 H2D(+3-22). In certain embodiments, the target region is DNM2 H2D(+2-23) . In certain embodiments, the target region is DNM2 H2D(+1-24). In certain embodiments, the target region is DNM2 H2D(-1-25). In certain embodiments, the target region is DNM2 H2D(-2-26). In certain embodiments, the target region is DNM2 H2D(-3-27). In certain embodiments, the target region is DNM2 H2D(-4-28). In certain embodiments, the target region is DNM2 H2D(-5-29). In certain embodiments, the target region is DNM2 H2D(-6-30). In certain embodiments, the target region is DNM2 H6A(-20+5). In certain embodiments, the target region is DNM2 H6A(-6+19). In certain embodiments, the target region is DNM2 H6A(-2+23). In certain embodiments, the target region is DNM2 H6A(+3+26). In certain embodiments, the target region is DNM2 H6A(+10+3). In certain embodiments, the target region is DNM2 H6A(+13+37). In certain embodiments, the target region is DNM2 H6A(+23+47). In certain embodiments, the target region is DNM2 H6A(+32+56). In certain embodiments, the target region is DNM2 H6A(+35+59). In certain embodiments, the target region is DNM2 H6A(+44+68). In certain embodiments, the target region is DNM2 H6A(+54+78). In certain embodiments, the target region is DNM2 H6A(+60+84). In certain embodiments, the target region is DNM2 H6A(+63+87). In certain embodiments, the target region is DNM2 H6A(+88+112). In certainembodiments, the target region is DNM2 H6A(+96+119). In certain embodiments, the target region is DNM2 H6A(+105+129). In certain embodiments, the target region is DNM2 H6A(+121+145). In certain embodiments, the target region is DNM2 H6A(+130+154). In certain embodiments, the target region is DNM2 H6A(+132+156). In certain embodiments, the target region is DNM2 H6D (+6-19). In certain embodiments, the target region is DNM2 H6D (+15-10). In certain embodiments, the target region is DNM2 H6D (+17-8). In certain embodiments, the target region is DNM2 H7A(-15+10). In certain embodiments, the target region is DNM2 H7A(- 5+20). In certain embodiments, the target region is DNM2 H7A(+1+25). In certain embodiments, the target region is DNM2 H7A(+6+30). In certain embodiments, the target region is. In certain embodiments, the target region is DNM2 H7A(+22+46). In certain embodiments, the target region is DNM2 H7A(+29+53). In certain embodiments, the target region is DNM2 H7A(+41+65). In certain embodiments, the target region is DNM2 H7A(+51+75). In certain embodiments, the target region is DNM2 H7A(+57+81). In certain embodiments, the target region is DNM2 H7A(+62+86). In certain embodiments, the target region is DNM2 H7A(+72+96). In certain embodiments, the target region is DNM2 H7A(+74+98). In certain embodiments, the target region is DNM2 H7A(+81+105). In certain embodiments, the target region is DNM2 H7A(+91+115). In certain embodiments, the target region is DNM2 H7A(+110+134). In certain embodiments, the target region is DNM2 H7D(+8-16). In certain embodiments, the target region is DNM2 H7D(+9-16). In certain embodiments, the target region is DNM2 H7D(+21-4). In certain embodiments, the target region is DNM2 H8A(-20+5). In certain embodiments, the target region is DNM2 H8A(-14+11). In certain embodiments, the target region is DNM2 H8A(-7+18). In certain embodiments, the target region is DNM2 H8A(-6+19). In certain embodiments, the target region is DNM2 H8A(-2+23). In certain embodiments, the target region is DNM2 H8A(+5+29). In certain embodiments, the target region is DNM2 H8A(+18+42). In certain embodiments, the target region is DNM2 H8A(+21+45). In certain embodiments, the target region is DNM2 H8A(+27+51). In certain embodiments, the target region is DNM2 H8A(+36+60). In certain embodiments, the target region is DNM2 H8A(+46+70). In certain embodiments, the target region is DNM2 H8A(+51+75). In certain embodiments, the target region is DNM2 H8A(+56+80). In certain embodiments, the target region is DNM2 H8A(+65+88). In certain embodiments, the target region is DNM2 H8A(+76+100). In certain embodiments, the target region is DNM2 H8A(+83+107). In certain embodiments, the target region is DNM2 H8A(+96+119). In certain embodiments, the target region is DNM2 H8A(+105+129). In certain embodiments, the target region is DNM2 H8D(+18-7). In certain embodiments, the target region is DNM2 H8D(+10-15). In certain embodiments, the target region is DNM2 H9A(-12+13). In certain embodiments, the target region is DNM2 H9A(-5+20). In certain embodiments, the target region is DNM2H9A(+1+25). In certain embodiments, the target region is DNM2 H9A(+6+30). In certain embodiments, the target region is DNM2 H9A(+16+40). In certain embodiments, the target region is DNM2 H9A(+25+49). In certain embodiments, the target region is DNM2 H9A(+36+60). In certain embodiments, the target region is DNM2 H9A(+37+61). In certain embodiments, the target region is DNM2 H9A(+42+66). In certain embodiments, the target region is DNM2 H9A(+43+62). In certain embodiments, the target region is DNM2 H9A(+43+63). In certain embodiments, the target region is DNM2 H9A(+43+64). In certain embodiments, the target region is DNM2 H9A(+43+65). In certain embodiments, the target region is DNM2 H9A(+43+66). In certain embodiments, the target region is DNM2 H9A(+43+67). In certain embodiments, the target region is DNM2 H9A(+44+67). In certain embodiments, the target region is DNM2 H9A(+44+68). In certain embodiments, the target region is DNM2 H9A(+45+67). In certain embodiments, the target region is DNM2 H9A (+46+67). In certain embodiments, the target region is DNM2 H9A(+47+67). In certain embodiments, the target region is DNM2 H9A(+48+67). In certain embodiments, the target region is DNM2 H9D(+24-1). In certain embodiments, the target region is DNM2 H9D(+23-2). In certain embodiments, the target region is DNM2 H9D(+22-3). In certain embodiments, the target region is DNM2 H9D(+21-4). In certain embodiments, the target region is DNM2 H9D(+20-5). In certain embodiments, the target region is DNM2 H9D(+19-6). In certain embodiments, the target region is DNM2 H9D (+18-7). In certain embodiments, the target region is DNM2 H9D(+17-8). In certain embodiments, the target region is DNM2 H9D(+16-9). In certain embodiments, the target region is DNM2 H9D(+15-10). In certain embodiments, the target region is DNM2 H9D(+14-11). In certain embodiments, the target region is DNM2 H9D(+13-12). In certain embodiments, the target region is DNM2 H9D(+12-13). In certain embodiments, the target region is DNM2 H9D(+11-14). In certain embodiments, the target region is DNM2 H9D(+10-15). In certain embodiments, the target region is DNM2 H9D(+9-16). In certain embodiments, the target region is DNM2 H9D(+8-12). In certain embodiments, the target region is DNM2 H9D(+8-13). In certain embodiments, the target region is DNM2 H9D(+8-14). In certain embodiments, the target region is DNM2 H9D(+8-15). In certain embodiments, the target region is DNM2 H9D(+8-17). In certain embodiments, the target region is DNM2 H9D(+7-18). In certain embodiments, the target region is DNM2 H9D(+7-17). In certain embodiments, the target region is DNM2 H9D(+6-19). In certain embodiments, the target region is DNM2 H9D(+6-17). In certain embodiments, the target region is DNM2 H9D(+5-17). In certain embodiments, the target region is DNM2 H9D(+5-20). In certain embodiments, the target region is DNM2 H9D(+4-17). In certain embodiments, the target region is DNM2 H9D(+4-21). In certain embodiments, the target region is DNM2 H9D(+3-17). In certain embodiments, the target region is DNM2 H9D(+3-22). In certain embodiments, the target region is DNM2 H12A(-13+12).In certain embodiments, the target region is DNM2 H12A(-3+22). In certain embodiments, the target region is DNM2 H12A(+4+28). In certain embodiments, the target region is DNM2 H12A(+7+31). In certain embodiments, the target region is DNM2 H12A(+10+34). In certain embodiments, the target region is DNM2 H12A(+11+35). In certain embodiments, the target region is DNM2 H12A(+12+36). In certain embodiments, the target region is DNM2 H12A(+13+37). In certain embodiments, the target region is DNM2 H12A(+14+38). In certain embodiments, the target region is DNM2 H12A(+15+39). In certain embodiments, the target region is DNM2 H12A(+16+40). In certain embodiments, the target region is DNM2 H12A(+17+41). In certain embodiments, the target region is DNM2 H12A(+18+42). In certain embodiments, the target region is DNM2 H12A(+19+43). In certain embodiments, the target region is DNM2 H12A(+20+44). In certain embodiments, the target region is DNM2 H12A(+25+44). In certain embodiments, the target region is DNM2 H12A(+25+45). In certain embodiments, the target region is DNM2 H12A(+25+46). In certain embodiments, the target region is DNM2 H12A(+25+47). In certain embodiments, the target region is DNM2 H12A(+25+48). In certain embodiments, the target region is DNM2 H12A(+25+49). In certain embodiments, the target region is DNM2 H12A(+26+49). In certain embodiments, the target region is DNM2 H12A(+27+49). In certain embodiments, the target region is DNM2 H12A(+28+49). In certain embodiments, the target region is DNM2 H12A(+29+49). In certain embodiments, the target region is DNM2 H12A(+29+53). In certain embodiments, the target region is DNM2 H12A(+30+49). In certain embodiments, the target region is DNM2 H12A(+30+54). In certain embodiments, the target region is DNM2 H12A(+36+60). In certain embodiments, the target region is DNM2 H12A(+37+61). In certain embodiments, the target region is DNM2 H12A(+43+67). In certain embodiments, the target region is DNM2 H12D(+22- 3). In certain embodiments, the target region is DNM2 H12D(+20-5). In certain embodiments, the target region is DNM2 H12D(+15-10). In certain embodiments, the target region is DNM2 H13A(-27-3). In certain embodiments, the target region is DNM2 H13A(-26-2). In certain embodiments, the target region is DNM2 H13A(-25-1). In certain embodiments, the target region is DNM2 H13A(-24+1). In certain embodiments, the target region is DNM2 H13A(-23+2). In certain embodiments, the target region is DNM2 H13A(-22+3). In certain embodiments, the target region is DNM2 H13A(-21+4). In certain embodiments, the target region is DNM2 H13A(- 20+5). In certain embodiments, the target region is DNM2 H13A(-19+6). In certain embodiments, the target region is DNM2 H13A(-18+7). In certain embodiments, the target region is DNM2 H13A(-17+8). In certain embodiments, the target region is DNM2 H13A(-16+9). In certain embodiments, the target region is DNM2 H13A(-15+10). In certain embodiments, the target region is DNM2 H13A(-14+11). In certain embodiments, the target region is DNM2 H13A(-13+12). In certain embodiments, the target region is DNM2 H13A(-11+14). In certain embodiments, the target region is DNM2 H13A(-10+15). In certain embodiments, the target region is DNM2 H13A(-9+16). In certain embodiments, the target region is DNM2 H13A(-8+17). In certain embodiments, the target region is DNM2 H13A(-7+18). In certain embodiments, the target region is DNM2 H13A(-6+19). In certain embodiments, the target region is DNM2 H13A(- 5+20). In certain embodiments, the target region is DNM2 H13A(-4+21). In certain embodiments, the target region is DNM2 H13A(-3+22). In certain embodiments, the target region is DNM2 H13A(-2+23). In certain embodiments, the target region is DNM2 H13A(-1+24). In certain embodiments, the target region is DNM2 H13A(+1+25). In certain embodiments, the target region is DNM2 H13A(+2+25). In certain embodiments, the target region is DNM2 H13A(+3+27). In certain embodiments, the target region is DNM2 H13A(+4+23). In certain embodiments, the target region is DNM2 H13A(+4+24). In certain embodiments, the target region is DNM2 H13A(+4+25). In certain embodiments, the target region is DNM2 H13A(+4+26). In certain embodiments, the target region is DNM2 H13A(+4+27). In certain embodiments, the target region is DNM2 H13A(+4+28). In certain embodiments, the target region is DNM2 H13A(+5+28). In certain embodiments, the target region is DNM2 H13A(+6+28). In certain embodiments, the target region is DNM2 H13A(+6+30). In certain embodiments, the target region is DNM2 H13A(+7+28). In certain embodiments, the target region is DNM2 H13A(+8+28). In certain embodiments, the target region is DNM2 H13A(+9+28). In certain embodiments, the target region is DNM2 H13A(+16+40). In certain embodiments, the target region is DNM2 H13D(+22-3). In certain embodiments, the target region is DNM2 H13D(+7-18). In certain embodiments, the target region is DNM2 H16A(-21+3). In certain embodiments, the target region is DNM2 H16A(-13+12). In certain embodiments, the target region is DNM2 H16A(- 6+19). In certain embodiments, the target region is DNM2 H16A(+6+30). In certain embodiments, the target region is DNM2 H16A(+15+39). In certain embodiments, the target region is DNM2 H16A(+26+50). In certain embodiments, the target region is DNM2 H16A(+36+60). In certain embodiments, the target region is DNM2 H16A(+45+69). In certain embodiments, the target region is DNM2 H16A(+55+79). In certain embodiments, the target region is DNM2 H16A(+66+90). In certain embodiments, the target region is DNM2 H16A(+75+99). In certain embodiments, the target region is DNM2 H16A(+82+106). In certain embodiments, the target region is DNM2 H16D(+19-6). In certain embodiments, the target region is DNM2 H16D(+11-14). In certain embodiments, the target region is DNM2 H19A(- 11+14). In certain embodiments, the target region is DNM2 H19A(-4+21). In certain embodiments, the target region is DNM2 H19A(+1+25). In certain embodiments, the target region is DNM2 H19A(+7+31). In certain embodiments, the target region is DNM2H19A(+16+40). In certain embodiments, the target region is DNM2 H19A(+26+50). In certain embodiments, the target region is DNM2 H19A(+37+61). In certain embodiments, the target region is DNM2 H19A(+47+71). In certain embodiments, the target region is DNM2 H19A(+56+80). In certain embodiments, the target region is DNM2 H19A(+66+90). In certain embodiments, the target region is DNM2 H19A(+76+100). In certain embodiments, the target region is DNM2 H19A(+86+110). In certain embodiments, the target region is DNM2 H19A(+96+120). In certain embodiments, the target region is DNM2 H19A(+106+130). In certain embodiments, the target region is DNM2 H19A(+117+141). In certain embodiments, the target region is DNM2 H19A(+127+151). In certain embodiments, the target region is DNM2 H19A(+137+161). In certain embodiments, the target region is DNM2 H19A(+147+171). In certain embodiments, the target region is DNM2 H19A(+157+181). In certain embodiments, the target region is DNM2 H19A(+166+189). In certain embodiments, the target region is DNM2 H19A(+191+215). In certain embodiments, the target region is DNM2 H19A(+200+224). In certain embodiments, the target region is DNM2 H19D(+23-2). In certain embodiments, the target region is DNM2 H19D(+17-8). In certain embodiments, the target region is DNM2 H19D(+10-15).

[0414] In certain embodiments, the targeting sequence is selected from: SEQ ID NO: 67 (CGGGGAAGGAAGTCCCTGTGAGGGG); SEQ ID NO: 68 (CGCGGBGAAGGAAGTCCCTGTGAG); SEQ ID NO: 69 (ATTCCTGAACCGCGBGGAAGGAAGT); SEQ ID NO: 70 (CCGGGTGACGATTCCTGAACCGC); SEQ ID NO: 71 (AGAGGCCGCCGGGTGACGATTCCTG); SEQ ID NO: 72 (TGAGAGGCCGCCGGGTGACGATTCC); SEQ ID NO: 73 (AGAATGAGAGGCCGCCGGGTGACGA); SEQ ID NO: 74 (GATGAGCTGCAGAATGAGAGGCCGC); SEQ ID NO: 75 (TTTTGAGAAGATGAGCTGCAGAATG); SEQ ID NO: 76 (GTTTTTGAGAAGATGAGCTGCAGAA); SEQ ID NO: 77 (TTTACCTGTTTTTGAGAAGATGAGC); SEQ ID NO: 78 (GCCCCATTTTACCTGTTTTTGAGAA); SEQ ID NO: 79 (CGCCCCATTTTACCTGTTTTTGAGA); SEQ ID NO: 80 (CCGCCCCATTTTACCTGTTTTTGAG); SEQ ID NO: 81 (GCCGCCCCATTTTACCTGTTTTTGA); SEQ ID NO: 82 (GGCCGCCCCATTTTACCTGTTTTTG); SEQ ID NO: 83 (AGGCCGCCCCATTTTACCTGTTTTT); SEQ ID NO: 84 (CAGGCCGCCCCATTTTACCTGTTTT);SEQ ID NO: 85 (TCAGGCCGCCCCATTTTACCTGTTT); SEQ ID NO: 86 (CTCAGGCCGCCCCATTTTACCTGTT); SEQ ID NO: 87 (CCTCAGGCCGCCCCATTTTACCTGT); SEQ ID NO: 88 (ACCTCAGGCCGCCCCATTTTACCTG); SEQ ID NO: 89 (AACCTCAGGCCGCCCCATTTTACCT); SEQ ID NO: 90 (GAACCTCAGGCCGCCCCATTTTACC); SEQ ID NO: 91 (TGAACCTCAGGCCGCCCCATTTTAC); SEQ ID NO: 92 (CTGAACCTCAGGCCGCCCCATTTTA); SEQ ID NO: 93 (GCTGAACCTCAGGCCGCCCCATTTT); SEQ ID NO: 94 (TGCTGAACCTCAGGCCGCCCCATTT); SEQ ID NO: 95 (CTGCTGAACCTCAGGCCGCCCCATT); SEQ ID NO: 96 (CCTGCTGAACCTCAGGCCGCCCCAT); SEQ ID NO: 97 (GTAGCCTGTGGGGAGAGGCAGTCAG); SEQ ID NO: 98 (TTCACCACGCCAATGTAGCCTGTGG); SEQ ID NO: 99 (GCGGTTCACCACGCCAATGTAGCCT); SEQ ID NO: 100 (GCTGCGGTTCACCACGCCAATGTA); SEQ ID NO: 101 (TCCTTCTGGCTGCGGTTCACCACGC); SEQ ID NO: 102 (ATATCCTTCTGGCTGCGGTTCACCA); SEQ ID NO: 103 (CTTGCCCTCAATATCCTTCTGGCTG); SEQ ID NO: 104 (GATGTCCTTCTTGCCCTCAATATCC); SEQ ID NO: 105 (ACGGATGTCCTTCTTGCCCTCAATA); SEQ ID NO: 106 (CAGTGCTGCACGGATGTCCTTCTTG); SEQ ID NO: 107 (TCTCAGCTGCCAGTGCTGCACGGAT); SEQ ID NO: 108 (ACTTCCTCTCAGCTGCCAGTGCTGC); SEQ ID NO: 109 (AGAACTTCCTCTCAGCTGCCAGTGC); SEQ ID NO: 110 (TGCCGGTAGGCCGGGTGGGAGAGGA); SEQ ID NO: 111 (GGCCATGTGCCGGTAGGCCGGGTG); SEQ ID NO: 112 (CCATGCGGTCGGCCATGTGCCGGTA); SEQ ID NO: 113 (TGCAGATGTGGCGTGCCCATGCGGT); SEQ ID NO: 114 (AGCGTCTTCTGCAGATGTGGCGTGC); SEQ ID NO: 115 (TCAGCGTCTTCTGCAGATGTGGCGT); SEQ ID NO: 116 (GTGCAAACCCTTGCAGTACCTGATT); SEQ ID NO: 117 (CTTGCAGTACCTGATTCAGCGTCTT); SEQ ID NO: 118 (TGCAGTACCTGATTCAGCGTCTTCT); SEQ ID NO: 119 (TGGTCAGTTGCTGCAGGAGAGAGGT);SEQ ID NO: 120 (CGGATGTGGTTGGTCAGTTGCTGCA); SEQ ID NO: 121 (ACTCCCGGATGTGGTTGGTCAGTTG); SEQ ID NO: 122 (CAGCGACTCCCGGATGTGGTTGGTC); SEQ ID NO: 123 (GCCGGCAGCGACTCCCGGATGTGGT); SEQ ID NO: 124 (TGCTACGTAGGGCCGGCAGCGACTC); SEQ ID NO: 125 (TGTAGTTTGCTACGTAGGGCCGGCA); SEQ ID NO: 126 (AGCAGCTGGCTCTGTAGTTTGCTAC); SEQ ID NO: 127 (CTCCAGGGACAGCAGCTGGCTCTGT); SEQ ID NO: 128 (CTCCTTCTCCAGGGACAGCAGCTGG); SEQ ID NO: 129 (TCCACCTCCTTCTCCAGGGACAGCA); SEQ ID NO: 130 (CTTGTACTCCTCCACCTCCTTCTCC); SEQ ID NO: 131 (TTCTTGTACTCCTCCACCTCCTTCT); SEQ ID NO: 132 (CCGAAAGTTCTTGTACTCCTCCACC); SEQ ID NO: 133 (GGTCGTCGGGCCGAAAGTTCTTGTA); SEQ ID NO: 134 (GCTTTGGTTTTGCGGGTGGGGTCGT); SEQ ID NO: 135 (GTGCCGBGGTACATACTGCAGCAG); SEQ ID NO: 136 (GTGCCGGGGTACATACTGCAGCAGG); SEQ ID NO: 137 (ATACTGCAGCAGGGCTTTGGTTTTG); SEQ ID NO: 138 (CCATCCTATGAGGAAAAGGAAAAAG); SEQ ID NO: 139 (GCTGGACCATCCTATGAGGAAAAGG); SEQ ID NO: 140 (CCAAACTGCTGGACCATCCTATGAG); SEQ ID NO: 141 (CCCAAACTGCTGGACCATCCTATGA); SEQ ID NO: 142 (CCACCCCAAACTGCTGGACCATCCT); SEQ ID NO: 143 (CAAAATCCACCCCAAACTGCTGGAC); SEQ ID NO: 144 (TCGATCCTCTTCTCAAAATCCACCC); SEQ ID NO: 145 (CCCTCGATCCTCTTCTCAAAATCCA); SEQ ID NO: 146 (CCTGAGCCCTCGATCCTCTTCTCAA); SEQ ID NO: 147 (ACCTGATCTCCTGAGCCCTCGATCC); SEQ ID NO: 148 (CAGAGTGTCCACCTGATCTCCTGAG); SEQ ID NO: 149 (AGCTCCAGAGTGTCCACCTGATCTC); SEQ ID NO: 150 (CGGAGAGCTCCAGAGTGTCCACCTG); SEQ ID NO: 151 (GGCGCCCCCGGAGAGCTCCAGAGT); SEQ ID NO: 152 (GCGATTGATTCGGGCGCCCCCGGAG); SEQ ID NO: 153 (GGAAGATGCGATTGATTCGGGCGCC); SEQ ID NO: 154 (GGAACCGCTCGTGGAAGATGCGAT);SEQ ID NO: 155 (AGCTCAAATGGGAACCGCTCGTGGA); SEQ ID NO: 156 (GCACTACCTTCACCAGCTCAAATGG); SEQ ID NO: 157 (CCCGGGGGGCACTACCTTCACCAGC); SEQ ID NO: 158 (CGTCAAACTCCATCTGAGAAGAGAC); SEQ ID NO: 159 (TCCTTCTCGTCAAACTCCATCTGAG); SEQ ID NO: 160 (GTAAGTCCTTCTCGTCAAACTCCAT); SEQ ID NO: 161 (CCGTCGTAAGTCCTTCTCGTCAAAC); SEQ ID NO: 162 (AGCTGATCTCCCGTCGTAAGTCCTT); SEQ ID NO: 163 (TAATGGCATAGCTGATCTCCCGTCG); SEQ ID NO: 164 (ATGGATGTTCTTAATGGCATAGCTG); SEQ ID NO: 165 (CATGGATGTTCTTAATGGCATAGCT); SEQ ID NO: 166 (GACTCCATGGATGTTCTTAATGGCA); SEQ ID NO: 167 (CCATGGATGTTCTTAATGGC); SEQ ID NO: 168 TCCATGGATGTTCTTAATGGC); SEQ ID NO: 169 (CTCCATGGATGTTCTTAATGGC); SEQ ID NO: 170 (ACTCCATGGATGTTCTTAATGGC); SEQ ID NO: 171 (GACTCCATGGATGTTCTTAATGGC); SEQ ID NO: 172 (TGACTCCATGGATGTTCTTAATGGC); SEQ ID NO: 173 (TGACTCCATGGATGTTCTTAATGG); SEQ ID NO: 174 (CTGACTCCATGGATGTTCTTAATGG); SEQ ID NO: 175 (TGACTCCATGGATGTTCTTAATG); SEQ ID NO: 176 (TGACTCCATGGATGTTCTTAAT); SEQ ID NO: 177 (TGACTCCATGGATGTTCTTAA); SEQ ID NO: 178 (TGACTCCATGGATGTTCTTA); SEQ ID NO: 179 (CCTGACTCCATGGATGTTCTTAATG); SEQ ID NO: 180 (GCCTGACTCCATGGATGTTCTTAAT); SEQ ID NO: 181 (TGCCTGACTCCATGGATGTTCTTAA); SEQ ID NO: 182 (TTGCCTGACTCCATGGATGTTCTTA); SEQ ID NO: 183 (CTTGCCTGACTCCATGGATGTTCTT); SEQ ID NO: 184 (ACTTGCCTGACTCCATGGATGTTCT); SEQ ID NO: 185 (AACTTGCCTGACTCCATGGATGTTC); SEQ ID NO: 186 (GAACTTGCCTGACTCCATGGATGTT); SEQ ID NO: 187 (GGAACTTGCCTGACTCCATGGATGT); SEQ ID NO: 188 TGGAACTTGCCTGACTCCATGGATG); SEQ ID NO: 189 (GTGGAACTTGCCTGACTCCATGGAT);SEQ ID NO: 190 (CGTGGAACTTGCCTGACTCCATGGA); SEQ ID NO: 191 TCGTGGAACTTGCCTGACTCCATGG); SEQ ID NO: 192 (CTCGTGGAACTTGCCTGACTCCATG); SEQ ID NO: 193 (CCTCGTGGAACTTGCCTGACTCCAT); SEQ ID NO: 194 (TCCTCGTGGAACTTGCCTGACTCCA); SEQ ID NO: 195 (TCCTCGTGGAACTTGCCTGACTCCA); SEQ ID NO: 196 (TCGTGGAACTTGCCTGACTCC); SEQ ID NO: 197 (CTCGTGGAACTTGCCTGACTCC); SEQ ID NO: 198 (CCTCGTGGAACTTGCCTGACTCC); SEQ ID NO: 199 (CTCCTCGTGGAACTTGCCTGACTCC); SEQ ID NO: 200 (TCTCCTCGTGGAACTTGCCTGACTC); SEQ ID NO: 201 (CTCCTCGTGGAACTTGCCTGACTC); SEQ ID NO: 202 (CTCTCCTCGTGGAACTTGCCTGACT); SEQ ID NO: 203 (CTCCTCGTGGAACTTGCCTGACT); SEQ ID NO: 204 (CTCCTCGTGGAACTTGCCTGAC); SEQ ID NO: 205 (ACTCTCCTCGTGGAACTTGCCTGAC); SEQ ID NO: 206 (CTCCTCGTGGAACTTGCCTGA); SEQ ID NO: 207 (GACTCTCCTCGTGGAACTTGCCTGA); SEQ ID NO: 208 (CTCCTCGTGGAACTTGCCTG); SEQ ID NO: 209 (TGACTCTCCTCGTGGAACTTGCCTG); SEQ ID NO: 210 (CAGCAGAAGAATCTGGBGGAGAGCG); SEQ ID NO: 211 (CAATGTCGATCAGCAGAAGAATCTG); SEQ ID NO: 212 (ACTGCTCAATGTCGATCAGCAGAAG); SEQ ID NO: 213 (AGGACTGCTCAATGTCGATCAGCAG); SEQ ID NO: 214 (TGTAGGACTGCTCAATGTCGATCAG); SEQ ID NO: 215 (ATGTAGGACTGCTCAATGTCGATCA); SEQ ID NO: 216 (GATGTAGGACTGCTCAATGTCGATC); SEQ ID NO: 217 (TGATGTAGGACTGCTCAATGTCGAT); SEQ ID NO: 218 (TTGATGTAGGACTGCTCAATGTCGA); SEQ ID NO: 219 (GTTGATGTAGGACTGCTCAATGTCG); SEQ ID NO: 220 (TGTTGATGTAGGACTGCTCAATGTC); SEQ ID NO: 221 (GTGTTGATGTAGGACTGCTCAATGT); SEQ ID NO: 222 (CGTGTTGATGTAGGACTGCTCAATG); SEQ ID NO: 223 (TCGTGTTGATGTAGGACTGCTCAAT); SEQ ID NO: 224 (TTCGTGTTGATGTAGGACTGCTCAA);SEQ ID NO: 225 (TTCGTGTTGATGTAGGACTG); SEQ ID NO: 226 (GTTCGTGTTGATGTAGGACTG); SEQ ID NO: 227 (GGTTCGTGTTGATGTAGGACTG); SEQ ID NO: 228 (TGGTTCGTGTTGATGTAGGACTG); SEQ ID NO: 229 (ATGGTTCGTGTTGATGTAGGACTG); SEQ ID NO: 230 (CATGGTTCGTGTTGATGTAGGACTG); SEQ ID NO: 231 (CATGGTTCGTGTTGATGTAGGACT); SEQ ID NO: 232 (CATGGTTCGTGTTGATGTAGGAC); SEQ ID NO: 233 (CATGGTTCGTGTTGATGTAGGA); SEQ ID NO: 234 (CATGGTTCGTGTTGATGTAGG); SEQ ID NO: 235 (TCCTCATGGTTCGTGTTGATGTAGG); SEQ ID NO: 236 (CATGGTTCGTGTTGATGTAG); SEQ ID NO: 237 (GTCCTCATGGTTCGTGTTGATGTAG); SEQ ID NO: 238 (GATGAAGTCCTCATGGTTCGTGTTG); SEQ ID NO: 239 (CGATGAAGTCCTCATGGTTCGTGTT); SEQ ID NO: 240 (CAAACCCGATGAAGTCCTCATGGTT); SEQ ID NO: 241 (TACTTGGCAAACCCGATGAAGTCCT); SEQ ID NO: 242 (CCTACTTGGCAAACCCGATGAAGTC); SEQ ID NO: 243 (AAGTACCTACTTGGCAAACCCGATG); SEQ ID NO: 244 (GAAACCAAAGAACAGACAGGGTTCA); SEQ ID NO: 245 (TGAAACCAAAGAACAGACAGGGTTC); SEQ ID NO: 246 (CTGAAACCAAAGAACAGACAGGGTT); SEQ ID NO: 247 (ACTGAAACCAAAGAACAGACAGGGT); SEQ ID NO: 248 (CACTGAAACCAAAGAACAGACAGGG); SEQ ID NO: 249 (GCACTGAAACCAAAGAACAGACAGG); SEQ ID NO: 250 (GGCACTGAAACCAAAGAACAGACAG); SEQ ID NO: 251 (GGGCACTGAAACCAAAGAACAGACA); SEQ ID NO: 252 (TGGGCACTGAAACCAAAGAACAGAC); SEQ ID NO: 253 (CTGGGCACTGAAACCAAAGAACAGA); SEQ ID NO: 254 (GCTGGGCACTGAAACCAAAGAACAG); SEQ ID NO: 255 (TGCTGGGCACTGAAACCAAAGAACA); SEQ ID NO: 256 (CTGCTGGGCACTGAAACCAAAGAAC); SEQ ID NO: 257 (TCTGCTGGGCACTGAAACCAAAGAA); SEQ ID NO: 258 (CTCTGCTGGGCACTGAAACCAAAGA); SEQ ID NO: 259 (TCCTCTGCTGGGCACTGAAACCAAA);SEQ ID NO: 260 (CTCCTCTGCTGGGCACTGAAACCAA); SEQ ID NO: 261 (GCTCCTCTGCTGGGCACTGAAACCA); SEQ ID NO: 262 (TGCTCCTCTGCTGGGCACTGAAACC); SEQ ID NO: 263 (GTGCTCCTCTGCTGGGCACTGAAAC); SEQ ID NO: 264 (CGTGCTCCTCTGCTGGGCACTGAAA); SEQ ID NO: 265 (GCGTGCTCCTCTGCTGGGCACTGAA); SEQ ID NO: 266 (TGCGTGCTCCTCTGCTGGGCACTGA); SEQ ID NO: 267 (CTGCGTGCTCCTCTGCTGGGCACTG); SEQ ID NO: 268 (GCTGCGTGCTCCTCTGCTGGGCACT); SEQ ID NO: 269 (AGCTGCGTGCTCCTCTGCTGGGCAC); SEQ ID NO: 270 (CAGCTGCGTGCTCCTCTGCTGGGCA); SEQ ID NO: 271 (TCAGCTGCGTGCTCCTCTGCTGGGC); SEQ ID NO: 272 (TTCAGCTGCGTGCTCCTCTGCTGGG); SEQ ID NO: 273 (GCTGCGTGCTCCTCTGCTGG); SEQ ID NO: 274 (AGCTGCGTGCTCCTCTGCTGG); SEQ ID NO: 275 (CAGCTGCGTGCTCCTCTGCTGG); SEQ ID NO: 276 (TCAGCTGCGTGCTCCTCTGCTGG); SEQ ID NO: 277 (TTCAGCTGCGTGCTCCTCTGCTGG); SEQ ID NO: 278 (GTTCAGCTGCGTGCTCCTCTGCTGG); SEQ ID NO: 279 (GTTCAGCTGCGTGCTCCTCTGCTG); SEQ ID NO: 280 (GTTCAGCTGCGTGCTCCTCTGCT); SEQ ID NO: 281 (TTGTTCAGCTGCGTGCTCCTCTGCT); SEQ ID NO: 282 (GTTCAGCTGCGTGCTCCTCTGC); SEQ ID NO: 283 (GTTCAGCTGCGTGCTCCTCTG); SEQ ID NO: 284 (GTTCAGCTGCGTGCTCCTCT); SEQ ID NO: 285 (GGCTCTCTTCTTGTTCAGCTGCGTG); SEQ ID NO: 286 (TACCTGATTGGBGATGGCTCTCTTC); SEQ ID NO: 287 (TGCAGAGGBGTGTGCTACCTGATTG); SEQ ID NO: 288 (CTCCTGAGGGTGGAGGGAAAAGAG); SEQ ID NO: 289 (CTTCTCTTTCTCCTGAGGGTGGAGG); SEQ ID NO: 290 (TGTACTTCTTCTCTTTCTCCTGAGG); SEQ ID NO: 291 (CAGAGGCAGCATGTACTTCTTCTCT); SEQ ID NO: 292 (GAGGTTGTCCAGAGGCAGCATGTAC); SEQ ID NO: 293 (TCACGGATCTTGAGGTTGTCCAGAG); SEQ ID NO: 294 (CTTCTCCACATCACGGATCTTGAGG);SEQ ID NO: 295 (CATGAAGCCCTTCTCCACATCACGG); SEQ ID NO: 296 (GCTTGTTGGACATGAAGCCCTTCTC); SEQ ID NO: 297 (GGCGAAGACGTGCTTGTTGGACATG); SEQ ID NO: 298 (GTTGAAGATGGCGAAGACGTGCTTG); SEQ ID NO: 299 (GCTCCGTGTTGAAGATGGCGAAGAC); SEQ ID NO: 300 (CCTCACCTCTGCTCCGTGTTGAAGA); SEQ ID NO: 301 (CCTGGGCCCCTCACCTCTGCTCCGT); SEQ ID NO: 302 (ATGAAGGCCTTCGTCTGCGGGCAGG); SEQ ID NO: 303 (GTGGTGGATGAAGGCCTTCGTCTGC); SEQ ID NO: 304 (GCTCGTGGTGGATGAAGGCCTTCGT); SEQ ID NO: 305 (CCAGCAGCTCGTGGTGGATGAAGGC); SEQ ID NO: 306 (ATAGGTAGGCCAGCAGCTCGTGGTG); SEQ ID NO: 307 (GCCGAGGAGTATAGGTAGGCCAGCA); SEQ ID NO: 308 (TGCTCTGGTCTGCCGAGGAGTATAG); SEQ ID NO: 309 (TCCATGAGGCTGCTCTGGTCTGCCG); SEQ ID NO: 310 (GCCGACTCCTCCATGAGGCTGCTCT); SEQ ID NO: 311 (TGCCTGGTCAGCCGACTCCTCCATG); SEQ ID NO: 312 (CCCGCCGCTGTGCCTGGTCAGCCGA); SEQ ID NO: 313 (AGCATGTCGTCCCGCCGCTGTGCCT); SEQ ID NO: 314 (GTACATGCGCAGCATGTCGTCCCGC); SEQ ID NO: 315 (TGAGGGCATGGTACATGCGCAGCAT); SEQ ID NO: 316 (GAGCGCCTCCTTGAGGGCATGGTAC); SEQ ID NO: 317 (CGATGATGTTGAGCGCCTCCTTGAG); SEQ ID NO: 318 (CTGATGTCACCGATGATGTTGAGCG); SEQ ID NO: 319 (AGTGCTGGTGCTGATGTCACCGATG); SEQ ID NO: 320 (GCGTGGACACAGTGCTGGTGCTGAT); SEQ ID NO: 321 (GGGTACAGGCGTGGACACAGTGCT); SEQ ID NO: 322 (TGGAGCCAGGTGTCATCGACAGGCG); SEQ ID NO: 323 (CTGGCGCTCTGGAGCCAGGTGTCAT); SEQ ID NO: 324 (ACCTGTGGCTGCTGGCGCTCTGGAG); SEQ ID NO: 325 (TTCCGGACCTGTGGCTGCTGGCGCT); and SEQ ID NO: 326 (ACCAGGCTTCCGGACCTGTGGCTGC).

[0415] In certain embodiments, the targeting sequence is SEQ ID NO: 67. In certain embodiments, the targeting sequence is SEQ ID NO: 68. In certain embodiments, the targeting sequence is SEQ ID NO: 69. In certain embodiments, the targeting sequence is SEQ ID NO: 70.

[0416] In certain embodiments, the targeting sequence is SEQ ID NO: 71. In certain embodiments, the targeting sequence is SEQ ID NO: 72. In certain embodiments, the targeting sequence is SEQ ID NO: 73. In certain embodiments, the targeting sequence is SEQ ID NO: 74. In certain embodiments, the targeting sequence is SEQ ID NO: 75. In certain embodiments, the targeting sequence is SEQ ID NO: 76. In certain embodiments, the targeting sequence is SEQ ID NO: 77. In certain embodiments, the targeting sequence is SEQ ID NO: 78. In certain embodiments, the targeting sequence is SEQ ID NO: 79. In certain embodiments, the targeting sequence is SEQ ID NO: 80. In certain embodiments, the targeting sequence is SEQ ID NO: 81. In certain embodiments, the targeting sequence is SEQ ID NO: 82. In certain embodiments, the targeting sequence is SEQ ID NO: 83. In certain embodiments, the targeting sequence is SEQ ID NO: 84. In certain embodiments, the targeting sequence is SEQ ID NO: 85. In certain embodiments, the targeting sequence is SEQ ID NO: 86. In certain embodiments, the targeting sequence is SEQ ID NO: 87. In certain embodiments, the targeting sequence is SEQ ID NO: 88. In certain embodiments, the targeting sequence is SEQ ID NO: 89. In certain embodiments, the targeting sequence is SEQ ID NO: 90. In certain embodiments, the targeting sequence is SEQ ID NO: 91. In certain embodiments, the targeting sequence is SEQ ID NO: 92. In certain embodiments, the targeting sequence is SEQ ID NO: 93. In certain embodiments, the targeting sequence is SEQ ID NO: 94. In certain embodiments, the targeting sequence is SEQ ID NO: 95. In certain embodiments, the targeting sequence is SEQ ID NO: 96. In certain embodiments, the targeting sequence is SEQ ID NO: 97. In certain embodiments, the targeting sequence is SEQ ID NO: 98. In certain embodiments, the targeting sequence is SEQ ID NO: 99. In certain embodiments, the targeting sequence is SEQ ID NO: 100. In certain embodiments, the targeting sequence is SEQ ID NO: 101. In certain embodiments, the targeting sequence is SEQ ID NO: 102. In certain embodiments, the targeting sequence is SEQ ID NO: 103. In certain embodiments, the targeting sequence is SEQ ID NO: 104. In certain embodiments, the targeting sequence is SEQ ID NO: 105. In certain embodiments, the targeting sequence is SEQ ID NO: 106. In certain embodiments, the targeting sequence is SEQ ID NO: 107. In certain embodiments, the targeting sequence is SEQ ID NO: 108. In certain embodiments, the targeting sequence is SEQ ID NO: 109. In certain embodiments, the targeting sequence is SEQ ID NO: 110. In certain embodiments, the targeting sequence is SEQ ID NO: 111. In certain embodiments, the targeting sequence is SEQ ID NO: 112. In certain embodiments, the targeting sequence is SEQ ID NO: 113. In certain embodiments, the targeting sequence is SEQ ID NO: 114. In certain embodiments, the targeting sequence is SEQ ID NO: 115. In certain embodiments, the targeting sequence is SEQ ID NO: 116. In certain embodiments, the targeting sequence is SEQ ID NO: 117. In certain embodiments, the targeting sequence is SEQ ID NO:118. In certain embodiments, the targeting sequence is SEQ ID NO: 119. In certain embodiments, the targeting sequence is SEQ ID NO: 120. In certain embodiments, the targeting sequence is SEQ ID NO: 121. In certain embodiments, the targeting sequence is SEQ ID NO: 122. In certain embodiments, the targeting sequence is SEQ ID NO: 123. In certain embodiments, the targeting sequence is SEQ ID NO: 124. In certain embodiments, the targeting sequence is SEQ ID NO: 125. In certain embodiments, the targeting sequence is SEQ ID NO: 126. In certain embodiments, the targeting sequence is SEQ ID NO: 127. In certain embodiments, the targeting sequence is SEQ ID NO: 128. In certain embodiments, the targeting sequence is SEQ ID NO: 129. In certain embodiments, the targeting sequence is SEQ ID NO: 130. In certain embodiments, the targeting sequence is SEQ ID NO: 131. In certain embodiments, the targeting sequence is SEQ ID NO: 132. In certain embodiments, the targeting sequence is SEQ ID NO: 133. In certain embodiments, the targeting sequence is SEQ ID NO: 134. In certain embodiments, the targeting sequence is SEQ ID NO: 135. In certain embodiments, the targeting sequence is SEQ ID NO: 136. In certain embodiments, the targeting sequence is SEQ ID NO: 137. In certain embodiments, the targeting sequence is SEQ ID NO: 138. In certain embodiments, the targeting sequence is SEQ ID NO: 139. In certain embodiments, the targeting sequence is SEQ ID NO: 140. In certain embodiments, the targeting sequence is SEQ ID NO: 141. In certain embodiments, the targeting sequence is SEQ ID NO: 142. In certain embodiments, the targeting sequence is SEQ ID NO: 143. In certain embodiments, the targeting sequence is SEQ ID NO: 144. In certain embodiments, the targeting sequence is SEQ ID NO: 145. In certain embodiments, the targeting sequence is SEQ ID NO: 146. In certain embodiments, the targeting sequence is SEQ ID NO: 147. In certain embodiments, the targeting sequence is SEQ ID NO: 148. In certain embodiments, the targeting sequence is SEQ ID NO: 149. In certain embodiments, the targeting sequence is SEQ ID NO: 150. In certain embodiments, the targeting sequence is SEQ ID NO: 151. In certain embodiments, the targeting sequence is SEQ ID NO: 152. In certain embodiments, the targeting sequence is SEQ ID NO: 153. In certain embodiments, the targeting sequence is SEQ ID NO: 154. In certain embodiments, the targeting sequence is SEQ ID NO: 155. In certain embodiments, the targeting sequence is SEQ ID NO: 156. In certain embodiments, the targeting sequence is SEQ ID NO: 157. In certain embodiments, the targeting sequence is SEQ ID NO: 158. In certain embodiments, the targeting sequence is SEQ ID NO: 159. In certain embodiments, the targeting sequence is SEQ ID NO: 160. In certain embodiments, the targeting sequence is SEQ ID NO: 161. In certain embodiments, the targeting sequence is SEQ ID NO: 162. In certain embodiments, the targeting sequence is SEQ ID NO: 163. In certain embodiments, the targeting sequence is SEQ ID NO: 164. In certain embodiments, the targetingsequence is SEQ ID NO: 165. In certain embodiments, the targeting sequence is SEQ ID NO: 166. In certain embodiments, the targeting sequence is SEQ ID NO: 167. In certain embodiments, the targeting sequence is SEQ ID NO: 168. In certain embodiments, the targeting sequence is SEQ ID NO: 169. In certain embodiments, the targeting sequence is SEQ ID NO: 170. In certain embodiments, the targeting sequence is SEQ ID NO: 171. In certain embodiments, the targeting sequence is SEQ ID NO: 172. In certain embodiments, the targeting sequence is SEQ ID NO: 173. In certain embodiments, the targeting sequence is SEQ ID NO: 174. In certain embodiments, the targeting sequence is SEQ ID NO: 175. In certain embodiments, the targeting sequence is SEQ ID NO: 176. In certain embodiments, the targeting sequence is SEQ ID NO: 177. In certain embodiments, the targeting sequence is SEQ ID NO: 178. In certain embodiments, the targeting sequence is SEQ ID NO: 179. In certain embodiments, the targeting sequence is SEQ ID NO: 180. In certain embodiments, the targeting sequence is SEQ ID NO: 181. In certain embodiments, the targeting sequence is SEQ ID NO: 182. In certain embodiments, the targeting sequence is SEQ ID NO: 183. In certain embodiments, the targeting sequence is SEQ ID NO: 184. In certain embodiments, the targeting sequence is SEQ ID NO: 185. In certain embodiments, the targeting sequence is SEQ ID NO: 186. In certain embodiments, the targeting sequence is SEQ ID NO: 187. In certain embodiments, the targeting sequence is SEQ ID NO: 188. In certain embodiments, the targeting sequence is SEQ ID NO: 189. In certain embodiments, the targeting sequence is SEQ ID NO: 190. In certain embodiments, the targeting sequence is SEQ ID NO: 191. In certain embodiments, the targeting sequence is SEQ ID NO: 192. In certain embodiments, the targeting sequence is SEQ ID NO: 193. In certain embodiments, the targeting sequence is SEQ ID NO: 194. In certain embodiments, the targeting sequence is SEQ ID NO: 195. In certain embodiments, the targeting sequence is SEQ ID NO: 196. In certain embodiments, the targeting sequence is SEQ ID NO: 197. In certain embodiments, the targeting sequence is SEQ ID NO: 198. In certain embodiments, the targeting sequence is SEQ ID NO: 199. In certain embodiments, the targeting sequence is SEQ ID NO: 200. In certain embodiments, the targeting sequence is SEQ ID NO: 201. In certain embodiments, the targeting sequence is SEQ ID NO: 202. In certain embodiments, the targeting sequence is SEQ ID NO: 203. In certain embodiments, the targeting sequence is SEQ ID NO: 204. In certain embodiments, the targeting sequence is SEQ ID NO: 205. In certain embodiments, the targeting sequence is SEQ ID NO: 206. In certain embodiments, the targeting sequence is SEQ ID NO: 207. In certain embodiments, the targeting sequence is SEQ ID NO: 208. In certain embodiments, the targeting sequence is SEQ ID NO: 209. In certain embodiments, the targeting sequence is SEQ ID NO: 210. In certain embodiments, the targeting sequence is SEQ ID NO: 211. In certainembodiments, the targeting sequence is SEQ ID NO: 212. In certain embodiments, the targeting sequence is SEQ ID NO: 213. In certain embodiments, the targeting sequence is SEQ ID NO: 214. In certain embodiments, the targeting sequence is SEQ ID NO: 215. In certain embodiments, the targeting sequence is SEQ ID NO: 216. In certain embodiments, the targeting sequence is SEQ ID NO: 217. In certain embodiments, the targeting sequence is SEQ ID NO: 218. In certain embodiments, the targeting sequence is SEQ ID NO: 219. In certain embodiments, the targeting sequence is SEQ ID NO: 220. In certain embodiments, the targeting sequence is SEQ ID NO: 221. In certain embodiments, the targeting sequence is SEQ ID NO: 222. In certain embodiments, the targeting sequence is SEQ ID NO: 223. In certain embodiments, the targeting sequence is SEQ ID NO: 224. In certain embodiments, the targeting sequence is SEQ ID NO: 225. In certain embodiments, the targeting sequence is SEQ ID NO: 226. In certain embodiments, the targeting sequence is SEQ ID NO: 227. In certain embodiments, the targeting sequence is SEQ ID NO: 228. In certain embodiments, the targeting sequence is SEQ ID NO: 229. In certain embodiments, the targeting sequence is SEQ ID NO: 230. In certain embodiments, the targeting sequence is SEQ ID NO: 231. In certain embodiments, the targeting sequence is SEQ ID NO: 232. In certain embodiments, the targeting sequence is SEQ ID NO: 233. In certain embodiments, the targeting sequence is SEQ ID NO: 234. In certain embodiments, the targeting sequence is SEQ ID NO: 235. In certain embodiments, the targeting sequence is SEQ ID NO: 236. In certain embodiments, the targeting sequence is SEQ ID NO: 237. In certain embodiments, the targeting sequence is SEQ ID NO: 238. In certain embodiments, the targeting sequence is SEQ ID NO: 239. In certain embodiments, the targeting sequence is SEQ ID NO: 240. In certain embodiments, the targeting sequence is SEQ ID NO: 241. In certain embodiments, the targeting sequence is SEQ ID NO: 242. In certain embodiments, the targeting sequence is SEQ ID NO: 243. In certain embodiments, the targeting sequence is SEQ ID NO: 244. In certain embodiments, the targeting sequence is SEQ ID NO: 245. In certain embodiments, the targeting sequence is SEQ ID NO: 246. In certain embodiments, the targeting sequence is SEQ ID NO: 247. In certain embodiments, the targeting sequence is SEQ ID NO: 248. In certain embodiments, the targeting sequence is SEQ ID NO: 249. In certain embodiments, the targeting sequence is SEQ ID NO: 250. In certain embodiments, the targeting sequence is SEQ ID NO: 251. In certain embodiments, the targeting sequence is SEQ ID NO: 252. In certain embodiments, the targeting sequence is SEQ ID NO: 253. In certain embodiments, the targeting sequence is SEQ ID NO: 254. In certain embodiments, the targeting sequence is SEQ ID NO: 255. In certain embodiments, the targeting sequence is SEQ ID NO: 256. In certain embodiments, the targeting sequence is SEQ ID NO: 257. In certain embodiments, the targeting sequence is SEQ ID NO:258. In certain embodiments, the targeting sequence is SEQ ID NO: 259. In certain embodiments, the targeting sequence is SEQ ID NO: 260. In certain embodiments, the targeting sequence is SEQ ID NO: 261. In certain embodiments, the targeting sequence is SEQ ID NO: 262. In certain embodiments, the targeting sequence is SEQ ID NO: 263. In certain embodiments, the targeting sequence is SEQ ID NO: 264. In certain embodiments, the targeting sequence is SEQ ID NO: 265. In certain embodiments, the targeting sequence is SEQ ID NO: 266. In certain embodiments, the targeting sequence is SEQ ID NO: 267. In certain embodiments, the targeting sequence is SEQ ID NO: 268. In certain embodiments, the targeting sequence is SEQ ID NO: 269. In certain embodiments, the targeting sequence is SEQ ID NO: 270. In certain embodiments, the targeting sequence is SEQ ID NO: 271. In certain embodiments, the targeting sequence is SEQ ID NO: 272. In certain embodiments, the targeting sequence is SEQ ID NO: 273. In certain embodiments, the targeting sequence is SEQ ID NO: 274. In certain embodiments, the targeting sequence is SEQ ID NO: 275. In certain embodiments, the targeting sequence is SEQ ID NO: 276. In certain embodiments, the targeting sequence is SEQ ID NO: 277. In certain embodiments, the targeting sequence is SEQ ID NO: 278. In certain embodiments, the targeting sequence is SEQ ID NO: 279. In certain embodiments, the targeting sequence is SEQ ID NO: 280. In certain embodiments, the targeting sequence is SEQ ID NO: 281. In certain embodiments, the targeting sequence is SEQ ID NO: 282. In certain embodiments, the targeting sequence is SEQ ID NO: 283. In certain embodiments, the targeting sequence is SEQ ID NO: 284. In certain embodiments, the targeting sequence is SEQ ID NO: 285. In certain embodiments, the targeting sequence is SEQ ID NO: 286. In certain embodiments, the targeting sequence is SEQ ID NO: 287. In certain embodiments, the targeting sequence is SEQ ID NO: 288. In certain embodiments, the targeting sequence is SEQ ID NO: 289. In certain embodiments, the targeting sequence is SEQ ID NO: 290. In certain embodiments, the targeting sequence is SEQ ID NO: 291. In certain embodiments, the targeting sequence is SEQ ID NO: 292. In certain embodiments, the targeting sequence is SEQ ID NO: 293. In certain embodiments, the targeting sequence is SEQ ID NO: 294. In certain embodiments, the targeting sequence is SEQ ID NO: 295. In certain embodiments, the targeting sequence is SEQ ID NO: 296. In certain embodiments, the targeting sequence is SEQ ID NO: 297. In certain embodiments, the targeting sequence is SEQ ID NO: 298. In certain embodiments, the targeting sequence is SEQ ID NO: 299. In certain embodiments, the targeting sequence is SEQ ID NO: 300. In certain embodiments, the targeting sequence is SEQ ID NO: 301. In certain embodiments, the targeting sequence is SEQ ID NO: 302. In certain embodiments, the targeting sequence is SEQ ID NO: 303. In certain embodiments, the targeting sequence is SEQ ID NO: 304. In certain embodiments, the targetingsequence is SEQ ID NO: 305. In certain embodiments, the targeting sequence is SEQ ID NO: 306. In certain embodiments, the targeting sequence is SEQ ID NO: 307. In certain embodiments, the targeting sequence is SEQ ID NO: 308. In certain embodiments, the targeting sequence is SEQ ID NO: 309. In certain embodiments, the targeting sequence is SEQ ID NO: 310. In certain embodiments, the targeting sequence is SEQ ID NO: 311. In certain embodiments, the targeting sequence is SEQ ID NO: 312. In certain embodiments, the targeting sequence is SEQ ID NO: 313. In certain embodiments, the targeting sequence is SEQ ID NO: 314. In certain embodiments, the targeting sequence is SEQ ID NO: 315. In certain embodiments, the targeting sequence is SEQ ID NO: 316. In certain embodiments, the targeting sequence is SEQ ID NO: 317. In certain embodiments, the targeting sequence is SEQ ID NO: 318. In certain embodiments, the targeting sequence is SEQ ID NO: 319. In certain embodiments, the targeting sequence is SEQ ID NO: 320. In certain embodiments, the targeting sequence is SEQ ID NO: 321. In certain embodiments, the targeting sequence is SEQ ID NO: 322. In certain embodiments, the targeting sequence is SEQ ID NO: 323. In certain embodiments, the targeting sequence is SEQ ID NO: 324. In certain embodiments, the targeting sequence is SEQ ID NO: 325. In certain embodiments, the targeting sequence is SEQ ID NO: 326.

[0417] In certain embodiments, the target region is within the exon internal region of exon 2 (SEQ ID NO: 2), the intron 1 / exon 2 junction, the exon 2 / intron 2 junction, or the intron internal region of intron 2 (SEQ ID NO: 11) of the human DNM2 gene pre-mRNA. In certain embodiments, the target region of the human DNM2 gene pre-mRNA is within the 21stnucleotide to the 47thnucleotide of exon 2 measured from the 5′ end of exon 2 (SEQ ID NO: 2). In certain embodiments, the target region is a region within SEQ ID NO: 13. In certain embodiments, the target region is a region within DNM2 H2A(+21+47).

[0418] In certain embodiments, the target region of the human DNM2 gene pre-mRNA is within the 23rdnucleotide to the 51stnucleotide of exon 2 measured from the 5′ end of exon 2 (SEQ ID NO: 2). In certain embodiments, the target region is a region within SEQ ID NO: 14. In certain embodiments, the target region is a region within DNM2 H2A(+23+51).

[0419] In certain embodiments, the target region of the human DNM2 gene pre-mRNA is within the 46thnucleotide to the 72ndnucleotide of exon 2 measured from the 5′ end of exon 2 (SEQ ID NO: 2). In certain embodiments, the target region is a region within SEQ ID NO: 15. In certain embodiments, the target region is a region within DNM2 H2A(+46+72).

[0420] In certain embodiments, the target region of the human DNM2 gene pre-mRNA is within the 13thnucleotide of exon 2 measured from the 3′ end of exon 2 (SEQ ID NO: 2) to the 24thnucleotide of intron 2 measured from the 3′ end of exon 2. In certain embodiments, the targetregion is a region within SEQ ID NO: 16. In certain embodiments, the target region is a region within DNM2 H2D(+13-24).

[0421] In certain embodiments, the target region of the human DNM2 gene pre-mRNA is within the 13thnucleotide of exon 2 measured from the 3′ end of exon 2 (SEQ ID NO: 2) to the 14thnucleotide of intron 2 measured from the 3′ end of exon 2. In certain embodiments, the target region is a region within SEQ ID NO: 17. In certain embodiments, the target region is a region within DNM2 H2D(+13-14).

[0422] In certain embodiments, the target region of the human DNM2 gene pre-mRNA is within the 10thnucleotide of exon 2 measured from the 3′ end of exon 2 (SEQ ID NO: 2) to the 19thnucleotide of intron 2 measured from the 3′ end of exon 2. In certain embodiments, the target region is a region within SEQ ID NO: 18. In certain embodiments, the target region is a region within DNM2 H2D(+10-19).

[0423] In certain embodiments, the target region of the human DNM2 gene pre-mRNA is within the 9thnucleotide of exon 2 measured from the 3′ end of exon 2 (SEQ ID NO: 2) to the 18thnucleotide of intron 2 measured from the 3′ end of exon 2. In certain embodiments, the target region is a region within SEQ ID NO: 19. In certain embodiments, the target region is a region within DNM2 H2D(+9-18).

[0424] In certain embodiments, the target region of the human DNM2 gene pre-mRNA is within the 6thnucleotide of exon 2 measured from the 3′ end of exon 2 (SEQ ID NO: 2) to the 23rdnucleotide of intron 2 measured from the 3′ end of exon 2. In certain embodiments, the target region is a region within SEQ ID NO: 20. In certain embodiments, the target region is a region within DNM2 H2D(+6-23).

[0425] In certain embodiments, the target region of the human DNM2 gene pre-mRNA is within the 4thnucleotide of exon 2 measured from the 3′ end of exon 2 (SEQ ID NO: 2) to the 23rdnucleotide of intron 2 measured from the 3′ end of exon 2. In certain embodiments, the target region is a region within SEQ ID NO: 21. In certain embodiments, the target region is a region within DNM2 H2D(+4-23).

[0426] In certain embodiments, the target region of the human DNM2 gene pre-mRNA is within the 1stnucleotide to the 30thnucleotide of intron 2 (SEQ ID NO: 11) measured from the 3′ end of exon 2 (SEQ ID NO: 2). In certain embodiments, the target region is a region within SEQ ID NO: 22. In certain embodiments, the target region is a region within DNM2 H2D(-1-30).

[0427] In certain embodiments, the target region of the human DNM2 gene pre-mRNA is within the 1stnucleotide to the 29thnucleotide of intron 2 (SEQ ID NO: 11) measured from the 3′ end of exon 2 (SEQ ID NO: 2). In certain embodiments, the target region is a region within SEQ ID NO: 23. In certain embodiments, the target region is a region within DNM2 H2D(-1-29).

[0428] In certain embodiments, the target region of the human DNM2 gene pre-mRNA is DNM2 H2A (-10+15), DNM2 H2A(-7+17), DNM2 H2A(+3+27), DNM2 H2A(+15+37), DNM2 H2A(+21+45), DNM2 H2A(+23+47), DNM2 H2A(+27+51), DNM2 H2A(+37+61), DNM2 H2A(+46+70), DNM2 H2A (+48+72), DNM2 H2D(+20-5), DNM2 H2D (+13-12), DNM2 H2D(+12- 13), DNM2 H2D(+11-14), DNM2 H2D(+10-15), DNM2 H2D(+9-16), DNM2 H2D(+8-17), DNM2 H2D(+7-18), DNM2 H2D(+6-19), DNM2 H2D(+5-20), DNM2 H2D(+4-21), DNM2 H2D(+3-22), DNM2 H2D(+2-23), DNM2 H2D(+1-24), DNM2 H2D(-1-25), DNM2 H2D(-2-26), DNM2 H2D(-3- 27), DNM2 H2D(-4-28), DNM2 H2D(-5-29), or DNM2 H2D(-6-30).

[0429] In certain embodiments, the target region of the human DNM2 gene pre-mRNA is DNM2 H2D (+13-12), DNM2 H2D(+12-13), DNM2 H2D(+11-14), DNM2 H2D(+10-15), DNM2 H2D(+9- 16), DNM2 H2D(+8-17), DNM2 H2D(+7-18), DNM2 H2D(+6-19), DNM2 H2D(+5-20), DNM2 H2D(+4-21), DNM2 H2D(+3-22), DNM2 H2D(+2-23) , DNM2 H2D(+1-24), DNM2 H2D(-1-25), DNM2 H2D(-2-26), DNM2 H2D(-3-27), DNM2 H2D(-4-28), DNM2 H2D(-5-29), or DNM2 H2D(-6- 30).

[0430] In certain embodiments, the target region is DNM2 H2A(+21+45) or DNM2 H2A(+23+47). In certain embodiments, the target region is DNM2 H2A(+23+47) or DNM2 H2A(+27+51). In certain embodiments, the target region is DNM2 H2A(+46+70) or DNM2 H2A(+48+72).

[0431] In certain embodiments, the target region is DNM2 H2D(+13-12), DNM2 H2D(+12-13), DNM2 H2D(+11-14), DNM2 H2D(+10-15), DNM2 H2D(+9-16), DNM2 H2D(+8-17), DNM2 H2D(+7-18), DNM2 H2D(+6-19), DNM2 H2D(+5-20), DNM2 H2D(+4-21), DNM2 H2D(+3-22), DNM2 H2D(+2-23), or DNM2 H2D(+1-24). In certain embodiments, the target region is DNM2 H2D (+13-12), DNM2 H2D(+12-13), or DNM2 H2D(+11-14).

[0432] In certain embodiments, the target region is DNM2 H2D(+10-15), DNM2 H2D(+9-16), DNM2 H2D(+8-17), DNM2 H2D(+7-18), or DNM2 H2D(+6-19). In certain embodiments, the target region is DNM2 H2D(+9-16), DNM2 H2D(+8-17), or DNM2 H2D(+7-18). In certain embodiments, the target region is DNM2 H2D(+8-17).

[0433] In certain embodiments, the target region is DNM2 H2D(+6-19), DNM2 H2D(+5-20), DNM2 H2D(+4-21), DNM2 H2D(+3-22), DNM2 H2D(+2-23). In certain embodiments, the target region is DNM2 H2D(+4-21), DNM2 H2D(+3-22), or DNM2 H2D(+2-23). In certain embodiments, the target region is DNM2 H2D(+3-22).

[0434] In certain embodiments, the target region is DNM2 H2D(-1-25), DNM2 H2D(-2-26), DNM2 H2D(-3-27), DNM2 H2D(-4-28), DNM2 H2D(-5-29), or DNM2 H2D(-6-30). In certain embodiments, the target region is DNM2 H2D(-1-25), DNM2 H2D(-2-26), DNM2 H2D(-3-27), DNM2 H2D(-4-28), or DNM2 H2D(-5-29).

[0435] In certain embodiments, the target region of the human DNM2 gene pre-mRNA is DNM2 H2A (-10+15). In certain embodiments, the target region of the human DNM2 gene pre-mRNA is DNM2 H2A(-7+17). In certain embodiments, the target region of the human DNM2 gene pre- mRNA is DNM2 H2A(+3+27). In certain embodiments, the target region of the human DNM2 gene pre-mRNA is DNM2 H2A(+15+37). In certain embodiments, the target region of the human DNM2 gene pre-mRNA is DNM2 H2A(+37+61). In certain embodiments, the target region of the human DNM2 gene pre-mRNA is DNM2 H2D(+20-5).

[0436] In certain embodiments, the targeting sequence is selected from: SEQ ID NO: 67 (CGGGGAAGGAAGTCCCTGTGAGGGG); SEQ ID NO: 68 (CGCGGBGAAGGAAGTCCCTGTGAG); SEQ ID NO: 69 (ATTCCTGAACCGCGBGGAAGGAAGT); SEQ ID NO: 70 (CCGGGTGACGATTCCTGAACCGC); SEQ ID NO: 71 (AGAGGCCGCCGGGTGACGATTCCTG); SEQ ID NO: 72 (TGAGAGGCCGCCGGGTGACGATTCC); SEQ ID NO: 73 (AGAATGAGAGGCCGCCGGGTGACGA); SEQ ID NO: 74 (GATGAGCTGCAGAATGAGAGGCCGC); SEQ ID NO: 75 (TTTTGAGAAGATGAGCTGCAGAATG); SEQ ID NO: 76 (GTTTTTGAGAAGATGAGCTGCAGAA); SEQ ID NO: 77 (TTTACCTGTTTTTGAGAAGATGAGC); SEQ ID NO: 78 (GCCCCATTTTACCTGTTTTTGAGAA); SEQ ID NO: 79 (CGCCCCATTTTACCTGTTTTTGAGA); SEQ ID NO: 80 (CCGCCCCATTTTACCTGTTTTTGAG); SEQ ID NO: 81 (GCCGCCCCATTTTACCTGTTTTTGA); SEQ ID NO: 82 (GGCCGCCCCATTTTACCTGTTTTTG); SEQ ID NO: 83 (AGGCCGCCCCATTTTACCTGTTTTT); SEQ ID NO: 84 (CAGGCCGCCCCATTTTACCTGTTTT); SEQ ID NO: 85 (TCAGGCCGCCCCATTTTACCTGTTT); SEQ ID NO: 86 (CTCAGGCCGCCCCATTTTACCTGTT); SEQ ID NO: 87 (CCTCAGGCCGCCCCATTTTACCTGT); SEQ ID NO: 88 (ACCTCAGGCCGCCCCATTTTACCTG); SEQ ID NO: 89 (AACCTCAGGCCGCCCCATTTTACCT); SEQ ID NO: 90 (GAACCTCAGGCCGCCCCATTTTACC); SEQ ID NO: 91 (TGAACCTCAGGCCGCCCCATTTTAC); SEQ ID NO: 92 (CTGAACCTCAGGCCGCCCCATTTTA); SEQ ID NO: 93 (GCTGAACCTCAGGCCGCCCCATTTT);SEQ ID NO: 94 (TGCTGAACCTCAGGCCGCCCCATTT); SEQ ID NO: 95 (CTGCTGAACCTCAGGCCGCCCCATT); and SEQ ID NO: 96 (CCTGCTGAACCTCAGGCCGCCCCAT), wherein B is an abasic subunit or guanine.

[0437] In certain embodiments, the targeting sequence is selected from: SEQ ID NO: 78 (GCCCCATTTTACCTGTTTTTGAGAA); SEQ ID NO: 79 (CGCCCCATTTTACCTGTTTTTGAGA); SEQ ID NO: 80 (CCGCCCCATTTTACCTGTTTTTGAG); SEQ ID NO: 81 (GCCGCCCCATTTTACCTGTTTTTGA); SEQ ID NO: 82 (GGCCGCCCCATTTTACCTGTTTTTG); SEQ ID NO: 83 (AGGCCGCCCCATTTTACCTGTTTTT); SEQ ID NO: 84 (CAGGCCGCCCCATTTTACCTGTTTT); SEQ ID NO: 85 (TCAGGCCGCCCCATTTTACCTGTTT); SEQ ID NO: 86 (CTCAGGCCGCCCCATTTTACCTGTT); SEQ ID NO: 87 (CCTCAGGCCGCCCCATTTTACCTGT); SEQ ID NO: 88 (ACCTCAGGCCGCCCCATTTTACCTG); SEQ ID NO: 89 (AACCTCAGGCCGCCCCATTTTACCT); SEQ ID NO: 90 (GAACCTCAGGCCGCCCCATTTTACC); SEQ ID NO: 91 (TGAACCTCAGGCCGCCCCATTTTAC); SEQ ID NO: 92 (CTGAACCTCAGGCCGCCCCATTTTA); SEQ ID NO: 93 (GCTGAACCTCAGGCCGCCCCATTTT); SEQ ID NO: 94 (TGCTGAACCTCAGGCCGCCCCATTT); SEQ ID NO: 95 (CTGCTGAACCTCAGGCCGCCCCATT); and SEQ ID NO: 96 (CCTGCTGAACCTCAGGCCGCCCCAT).

[0438] In certain embodiments, the targeting sequence is selected from: SEQ ID NO: 71 (AGAGGCCGCCGGGTGACGATTCCTG); and SEQ ID NO: 72 (TGAGAGGCCGCCGGGTGACGATTCC).

[0439] In certain embodiments, the targeting sequence is selected from: SEQ ID NO: 72 (TGAGAGGCCGCCGGGTGACGATTCC); and SEQ ID NO: 73 (AGAATGAGAGGCCGCCGGGTGACGA).

[0440] In certain embodiments, the targeting sequence is selected from: SEQ ID NO: 75 (TTTTGAGAAGATGAGCTGCAGAATG); and SEQ ID NO: 76 (GTTTTTGAGAAGATGAGCTGCAGAA).

[0441] In certain embodiments, the targeting sequence is selected from: SEQ ID NO: 78 (GCCCCATTTTACCTGTTTTTGAGAA);SEQ ID NO: 79 (CGCCCCATTTTACCTGTTTTTGAGA); SEQ ID NO: 80 (CCGCCCCATTTTACCTGTTTTTGAG); SEQ ID NO: 81 (GCCGCCCCATTTTACCTGTTTTTGA); SEQ ID NO: 82 (GGCCGCCCCATTTTACCTGTTTTTG); SEQ ID NO: 83 (AGGCCGCCCCATTTTACCTGTTTTT); SEQ ID NO: 84 (CAGGCCGCCCCATTTTACCTGTTTT); SEQ ID NO: 85 (TCAGGCCGCCCCATTTTACCTGTTT); SEQ ID NO: 86 (CTCAGGCCGCCCCATTTTACCTGTT); SEQ ID NO: 87 (CCTCAGGCCGCCCCATTTTACCTGT); SEQ ID NO: 88 (ACCTCAGGCCGCCCCATTTTACCTG); SEQ ID NO: 89 (AACCTCAGGCCGCCCCATTTTACCT); and SEQ ID NO: 90 (GAACCTCAGGCCGCCCCATTTTACC).

[0442] In certain embodiments, the targeting sequence is selected from: SEQ ID NO: 78 (GCCCCATTTTACCTGTTTTTGAGAA); SEQ ID NO: 79 (CGCCCCATTTTACCTGTTTTTGAGA); and SEQ ID NO: 80 (CCGCCCCATTTTACCTGTTTTTGAG).

[0443] In certain embodiments, the targeting sequence is selected from: SEQ ID NO: 81 (GCCGCCCCATTTTACCTGTTTTTGA); SEQ ID NO: 82 (GGCCGCCCCATTTTACCTGTTTTTG); SEQ ID NO: 83 (AGGCCGCCCCATTTTACCTGTTTTT); SEQ ID NO: 84 (CAGGCCGCCCCATTTTACCTGTTTT); and SEQ ID NO: 85 (TCAGGCCGCCCCATTTTACCTGTTT).

[0444] In certain embodiments, the targeting sequence is selected from: SEQ ID NO: 82 (GGCCGCCCCATTTTACCTGTTTTTG); SEQ ID NO: 83 (AGGCCGCCCCATTTTACCTGTTTTT); and SEQ ID NO: 84 (CAGGCCGCCCCATTTTACCTGTTTT).

[0445] In certain embodiments, the targeting sequence is SEQ ID NO: 83.

[0446] In certain embodiments, the targeting sequence is selected from: SEQ ID NO: 85 (TCAGGCCGCCCCATTTTACCTGTTT); SEQ ID NO: 86 (CTCAGGCCGCCCCATTTTACCTGTT); SEQ ID NO: 87 (CCTCAGGCCGCCCCATTTTACCTGT); SEQ ID NO: 88 (ACCTCAGGCCGCCCCATTTTACCTG); and SEQ ID NO: 89 (AACCTCAGGCCGCCCCATTTTACCT).

[0447] In certain embodiments, the targeting sequence is selected from: SEQ ID NO: 87 (CCTCAGGCCGCCCCATTTTACCTGT);SEQ ID NO: 88 (ACCTCAGGCCGCCCCATTTTACCTG); and SEQ ID NO: 89 (AACCTCAGGCCGCCCCATTTTACCT).

[0448] In certain embodiments, the targeting sequence is SEQ ID NO: 88.

[0449] In certain embodiments, the targeting sequence is selected from: SEQ ID NO: 91 (TGAACCTCAGGCCGCCCCATTTTAC); SEQ ID NO: 92 (CTGAACCTCAGGCCGCCCCATTTTA); SEQ ID NO: 93 (GCTGAACCTCAGGCCGCCCCATTTT); SEQ ID NO: 94 (TGCTGAACCTCAGGCCGCCCCATTT); SEQ ID NO: 95 (CTGCTGAACCTCAGGCCGCCCCATT); and SEQ ID NO: 96 (CCTGCTGAACCTCAGGCCGCCCCAT).

[0450] In certain embodiments, the targeting sequence is selected from: SEQ ID NO: 91 (TGAACCTCAGGCCGCCCCATTTTAC); SEQ ID NO: 92 (CTGAACCTCAGGCCGCCCCATTTTA); SEQ ID NO: 93 (GCTGAACCTCAGGCCGCCCCATTTT); SEQ ID NO: 94 (TGCTGAACCTCAGGCCGCCCCATTT); and SEQ ID NO: 95 (CTGCTGAACCTCAGGCCGCCCCATT).

[0451] In certain embodiments, the targeting sequence is selected from: SEQ ID NO: 67 (CGGGGAAGGAAGTCCCTGTGAGGGG); SEQ ID NO: 68 (CGCGGBGAAGGAAGTCCCTGTGAG); SEQ ID NO: 69 (ATTCCTGAACCGCGBGGAAGGAAGT); SEQ ID NO: 70 (CCGGGTGACGATTCCTGAACCGC); SEQ ID NO: 74 (GATGAGCTGCAGAATGAGAGGCCGC); and SEQ ID NO: 77 (TTTACCTGTTTTTGAGAAGATGAGC).

[0452] In certain embodiments, the target region is within the exon internal region of exon 9 (SEQ ID NO: 6), the intron 8 / exon 9 junction, or the exon 9 / intron 9 junction of the human DNM2 gene pre-mRNA.

[0453] In certain embodiments, the target region of the human DNM2 gene pre-mRNA is within the 36thnucleotide to the 61stnucleotide of exon 9 measured from the 5′ end of exon 9 (SEQ ID NO: 6). In certain embodiments, the target region is a region within SEQ ID NO: 24. In certain embodiments, the target region is a region within DNM2 H9A(+36+61).

[0454] In certain embodiments, the target region of the human DNM2 gene pre-mRNA i...

Claims

CLAIMS WHAT IS CLAIMED IS:

1. An antisense oligomer comprising a non-natural chemical backbone and a targeting sequence 13 to 30 bases in length that is complementary to a target region within a pre- mRNA of human dynamin 2 (DNM2) gene represented by SEQ ID NO: 1, wherein the target region is within an exon internal region, an intron internal region, an intron-exon junction, or an exon-intron junction of the human DNM2 gene pre-mRNA.

2. The antisense oligomer of claim 1, wherein the target region is within an exon internal region of the human DNM2 gene pre-mRNA selected from exon 2 (SEQ ID NO: 2), exon 6 (SEQ ID NO: 3), exon 7 (SEQ ID NO: 4), exon 8 (SEQ ID NO: 5), exon 9 (SEQ ID NO: 6), exon 12 (SEQ ID NO: 7), exon 13 (SEQ ID NO: 8), exon 16 (SEQ ID NO: 9), and exon 19 (SEQ ID NO: 10).

3. The antisense oligomer of claim 1 or 2, wherein the target region is within an exon internal region of the human DNM2 gene pre-mRNA selected from exon 2 (SEQ ID NO: 2), exon 9 (SEQ ID NO: 6), exon 12 (SEQ ID NO: 7), and exon 13 (SEQ ID NO: 8).

4. The antisense oligomer of claim 1, wherein the target region is within an intron-exon junction or an exon-intron junction region of the human DNM2 gene pre-mRNA selected from intron 1 / exon 2 junction, exon 2 / intron 2 junction, intron 5 / exon 6 junction, exon 6 / intron 6 junction, intron 6 / exon 7 junction, exon 7 / intron 7 junction, intron 7 / exon 8 junction, exon 8 / intron 8 junction, intron 8 / exon 9 junction, exon 9 / intron 9 junction, intron 11 / exon 12 junction, exon 12 / intron 12 junction, intron 12 / exon 13 junction, exon 13 / intron 13 junction, intron 15 / exon 16 junction, exon 16 / intron 16 junction, intron 18 / exon 19 junction, and exon 19 / intron 19 junction.

5. The antisense oligomer of claim 1 or 4, wherein the target region is within an intron-exon junction or an exon-intron junction of the human DNM2 gene pre-mRNA selected from intron 1 / exon 2 junction, exon 2 / intron 2 junction, intron 8 / exon 9 junction, exon 9 / intron 9 junction, intron 11 / exon 12 junction, exon 12 / intron 12 junction, intron 12 / exon 13 junction, and exon 13 / intron 13 junction.

6. The antisense oligomer of claim 1, wherein the target region is within an intron internal region of the human DNM2 gene pre-mRNA selected from intron 2 (SEQ ID NO: 11) and intron 12 (SEQ ID NO: 12).

7. The antisense oligomer of any one of claims 1-6, wherein the target region of the human DNM2 gene pre-mRNA is DNM2 H2A (-10+15), DNM2 H2A(-7+17), DNM2 H2A(+3+27), DNM2 H2A(+15+37), DNM2 H2A(+21+45), DNM2 H2A(+23+47), DNM2 H2A(+27+51), DNM2 H2A(+37+61), DNM2 H2A(+46+70), DNM2 H2A (+48+72), DNM2 H2D(+20-5),DNM2 H2D (+13-12), DNM2 H2D(+12-13), DNM2 H2D(+11-14), DNM2 H2D(+10-15), DNM2 H2D(+9-16), DNM2 H2D(+8-17), DNM2 H2D(+7-18), DNM2 H2D(+6-19), DNM2 H2D(+5-20), DNM2 H2D(+4-21), DNM2 H2D(+3-22), DNM2 H2D(+2-23), DNM2 H2D(+1-24), DNM2 H2D(-1-25), DNM2 H2D(-2-26), DNM2 H2D(-3-27), DNM2 H2D(-4- 28), DNM2 H2D(-5-29), DNM2 H2D(-6-30), DNM2 H9A(-12+13), DNM2 H9A(-5+20), DNM2 H9A(+1+25),DNM2 H9A(+6+30), DNM2 H9A(+16+40), DNM2 H9A(+25+49), DNM2 H9A(+36+60), DNM2 H9A(+37+61), DNM2 H9A(+42+66), DNM2 H9A(+43+62), DNM2 H9A(+43+63), DNM2 H9A(+43+64), DNM2 H9A(+43+65), DNM2 H9A(+43+66), DNM2 H9A(+43+67), DNM2 H9A(+44+67), DNM2 H9A(+44+68), DNM2 H9A(+45+67), DNM2 H9A (+46+67), DNM2 H9A(+47+67), DNM2 H9A(+48+67), DNM2 H9D(+24-1), DNM2 H9D(+23-2), DNM2 H9D(+22-3), DNM2 H9D(+21-4), DNM2 H9D(+20-5), DNM2 H9D(+19-6), DNM2 H9D (+18-7), DNM2 H9D(+17-8), DNM2 H9D(+16-9), DNM2 H9D(+15-10), DNM2 H9D(+14-11), DNM2 H9D(+13-12), DNM2 H9D(+12-13), DNM2 H9D(+11-14), DNM2 H9D(+10-15), DNM2 H9D(+9-16), DNM2 H9D(+8-12), DNM2 H9D(+8-13), DNM2 H9D(+8-14), DNM2 H9D(+8-15), DNM2 H9D(+8-17), DNM2 H9D(+7-18), DNM2 H9D(+7-17), DNM2 H9D(+6-19), DNM2 H9D(+6-17), DNM2 H9D(+5-17), DNM2 H9D(+5-20), DNM2 H9D(+4-17), DNM2 H9D(+4-21), DNM2 H9D(+3-17), DNM2 H9D(+3-22), DNM2 H12A(-13+12), DNM2 H12A(-3+22), DNM2 H12A(+4+28), DNM2 H12A(+7+31), DNM2 H12A(+10+34), DNM2 H12A(+11+35), DNM2 H12A(+12+36), DNM2 H12A(+13+37), DNM2 H12A(+14+38), DNM2 H12A(+15+39), DNM2 H12A(+16+40), DNM2 H12A(+17+41), DNM2 H12A(+18+42), DNM2 H12A(+19+43), DNM2 H12A(+20+44), DNM2 H12A(+25+44), DNM2 H12A(+25+45), DNM2 H12A(+25+46), DNM2 H12A(+25+47), DNM2 H12A(+25+48), DNM2 H12A(+25+49), DNM2 H12A(+26+49), DNM2 H12A(+27+49), DNM2 H12A(+28+49), DNM2 H12A(+29+49), DNM2 H12A(+29+53), DNM2 H12A(+30+49), DNM2 H12A(+30+54), DNM2 H12A(+36+60), DNM2 H12A(+37+61), DNM2 H12A(+43+67), DNM2 H12D(+22-3), DNM2 H12D(+20-5), DNM2 H12D(+15-10), DNM2 H12A(+4+28), DNM2 H12A(+7+31), DNM2 H12A(+10+34), DNM2 H12A(+11+35), DNM2 H12A(+12+36), DNM2 H12A(+13+37), DNM2 H12A(+14+38), DNM2 H12A(+15+39), DNM2 H12A(+16+40), DNM2 H12A(+17+41), DNM2 H12A(+18+42), DNM2 H12A(+19+43), DNM2 H12A(+20+44), DNM2 H12A(+25+44), DNM2 H12A(+25+45), DNM2 H12A(+25+46), DNM2 H12A(+25+47), DNM2 H12A(+25+48), DNM2 H12A(+25+49), DNM2 H12A(+26+49), DNM2 H12A(+27+49), DNM2 H12A(+28+49), DNM2 H12A(+29+49), DNM2 H12A(+29+53), DNM2 H12A(+30+49), DNM2 H12A(+30+54), DNM2 H12A(+36+60), DNM2 H12A(+37+61), DNM2H12A(+43+67), DNM2 H13A(-27-3), DNM2 H13A(-26-2), DNM2 H13A(-25-1), DNM2 H13A(-24+1), DNM2 H13A(-23+2), DNM2 H13A(-22+3), DNM2 H13A(-21+4), DNM2 H13A(-20+5), DNM2 H13A(-19+6), DNM2 H13A(-18+7), DNM2 H13A(-17+8), DNM2 H13A(-16+9), DNM2 H13A(-15+10), DNM2 H13A(-14+11), DNM2 H13A(-13+12), DNM2 H13A(-11+14), DNM2 H13A(-10+15), DNM2 H13A(-9+16), DNM2 H13A(-8+17), DNM2 H13A(-7+18), DNM2 H13A(-6+19), DNM2 H13A(-5+20), DNM2 H13A(-4+21), DNM2 H13A(-3+22), DNM2 H13A(-2+23), DNM2 H13A(-1+24), DNM2 H13A(+1+25), DNM2 H13A(+2+25), DNM2 H13A(+3+27), DNM2 H13A(+4+23), DNM2 H13A(+4+24), DNM2 H13A(+4+25), DNM2 H13A(+4+26), DNM2 H13A(+4+27), DNM2 H13A(+4+28), DNM2 H13A(+5+28), DNM2 H13A(+6+28), DNM2 H13A(+6+30), DNM2 H13A(+7+28), DNM2 H13A(+8+28), DNM2 H13A(+9+28), DNM2 H13A(+16+40), DNM2 H13D(+22-3), or DNM2 H13D(+7-18).

8. The antisense oligomer of claim 7, wherein the targeting sequence is selected from SEQ ID NOs: 67-326.

9. The antisense oligomer of any one of claims 1-6, wherein the target region is within the exon internal region of exon 2 (SEQ ID NO: 2), the intron 1 / exon 2 junction, the exon 2 / intron 2 junction, or the intron internal region of intron 2 (SEQ ID NO: 11) of the human DNM2 gene pre-mRNA.

10. The antisense oligomer of any one of claims 1-3 or 9, wherein the target region of the human DNM2 gene pre-mRNA is within the 21stnucleotide to the 47thnucleotide of exon 2 measured from the 5′ end of exon 2 (SEQ ID NO: 2).

11. The antisense oligomer of claim 10, wherein the target region is a region within SEQ ID NO:

13.

12. The antisense oligomer of any one of claims 1-3 or 9, wherein the target region of the human DNM2 gene pre-mRNA is within the 23rdnucleotide to the 51stnucleotide of exon 2 measured from the 5′ end of exon 2 (SEQ ID NO: 2).

13. The antisense oligomer of claim 12, wherein the target region is a region within SEQ ID NO:

14.

14. The antisense oligomer of any one of claims 1-3 or 9, wherein the target region of the human DNM2 gene pre-mRNA is within the 46thnucleotide to the 72ndnucleotide of exon 2 measured from the 5′ end of exon 2 (SEQ ID NO: 2).

15. The antisense oligomer of claim 14, wherein the target region is a region within SEQ ID NO:

15.

16. The antisense oligomer of any one of claims 1, 4-5, or 9, wherein the target region of the human DNM2 gene pre-mRNA is within the 13thnucleotide of exon 2 measured from theend of exon 2.

17. The antisense oligomer of claim 16, wherein the target region is a region within SEQ ID NO:

16.

18. The antisense oligomer of any one of claims 1, 4-5, 9, or 16-17, wherein the target region of the human DNM2 gene pre-mRNA is within the 13thnucleotide of exon 2 measured from the 3′ end of exon 2 (SEQ ID NO: 2) to the 14thnucleotide of intron 2 measured from the 3′ end of exon 2.

19. The antisense oligomer of claim 18, wherein the target region is a region within SEQ ID NO:

17.

20. The antisense oligomer of any one of claims 1, 4-5, 9, or 16-17, wherein the target region of the human DNM2 gene pre-mRNA is within the 10thnucleotide of exon 2 measured from the 3′ end of exon 2 (SEQ ID NO: 2) to the 19thnucleotide of intron 2 measured from the 3′ end of exon 2.

21. The antisense oligomer of claim 20, wherein the target region is a region within SEQ ID NO:

18.

22. The antisense oligomer of any one of claims 1, 4-5, 9, 16-17, or 20-21, wherein the target region of the human DNM2 gene pre-mRNA is within the 9thnucleotide of exon 2 measured from the 3′ end of exon 2 (SEQ ID NO: 2) to the 18thnucleotide of intron 2 measured from the 3′ end of exon 2.

23. The antisense oligomer of claim 22, wherein the target region is a region within SEQ ID NO:

19.

24. The antisense oligomer of any one of claims 1, 4-5, 9, or 16-17, wherein the target region of the human DNM2 gene pre-mRNA is within the 6thnucleotide of exon 2 measured from the 3′ end of exon 2 (SEQ ID NO: 2) to the 23rdnucleotide of intron 2 measured from the 3′ end of exon 2.

25. The antisense oligomer of claim 24, wherein the target region is a region within SEQ ID NO:

20.

26. The antisense oligomer of any one of claims 1, 4-5, 9, 16-17, or 24-25, wherein the target region of the human DNM2 gene pre-mRNA is within the 4thnucleotide of exon 2 measured from the 3′ end of exon 2 (SEQ ID NO: 2) to the 23rdnucleotide of intron 2 measured from the 3′ end of exon 2.

27. The antisense oligomer of claim 26, wherein the target region is a region within SEQ ID NO: 21.

28. The antisense oligomer of any one of claims 1, 6, or 9, wherein the target region of the human DNM2 gene pre-mRNA is within the 1stnucleotide to the 30thnucleotide of intron 2 (SEQ ID NO: 11) measured from the 3′ end of exon 2 (SEQ ID NO: 2).

29. The antisense oligomer of claim 28, wherein the target region is a region within SEQ ID NO:

22.

30. The antisense oligomer of any one of claims 1, 6, 9, or 28-29, wherein the target region of the human DNM2 gene pre-mRNA is within the 1stnucleotide to the 29thnucleotide of intron 2 (SEQ ID NO: 11) measured from the 3′ end of exon 2 (SEQ ID NO: 2).

31. The antisense oligomer of claim 30, wherein the target region is a region within SEQ ID NO:

23.

32. The antisense oligomer of any one of claims 1-31, wherein the target region of the human DNM2 gene pre-mRNA is DNM2 H2A (-10+15), DNM2 H2A(-7+17), DNM2 H2A(+3+27), DNM2 H2A(+15+37), DNM2 H2A(+21+45), DNM2 H2A(+23+47), DNM2 H2A(+27+51), DNM2 H2A(+37+61), DNM2 H2A(+46+70), DNM2 H2A (+48+72), DNM2 H2D(+20-5), DNM2 H2D (+13-12), DNM2 H2D(+12-13), DNM2 H2D(+11-14), DNM2 H2D(+10-15), DNM2 H2D(+9-16), DNM2 H2D(+8-17), DNM2 H2D(+7-18), DNM2 H2D(+6-19), DNM2 H2D(+5-20), DNM2 H2D(+4-21), DNM2 H2D(+3-22), DNM2 H2D(+2-23), DNM2 H2D(+1-24), DNM2 H2D(-1-25), DNM2 H2D(-2-26), DNM2 H2D(-3- 27), DNM2 H2D(-4-28), DNM2 H2D(-5-29), or DNM2 H2D(-6-30).

33. The antisense oligomer of claim 32, wherein the target region of the human DNM2 gene pre-mRNA is DNM2 H2D (+13-12), DNM2 H2D(+12-13), DNM2 H2D(+11-14), DNM2 H2D(+10-15), DNM2 H2D(+9-16), DNM2 H2D(+8-17), DNM2 H2D(+7-18), DNM2 H2D(+6-19), DNM2 H2D(+5-20), DNM2 H2D(+4-21), DNM2 H2D(+3-22), DNM2 H2D(+2-23) , DNM2 H2D(+1-24), DNM2 H2D(-1-25), DNM2 H2D(-2-26), DNM2 H2D(-3- 27), DNM2 H2D(-4-28), DNM2 H2D(-5-29), or DNM2 H2D(-6-30).

34. The antisense oligomer of any one of claims 1-3, 7, 9-11, or 32, wherein the target region is DNM2 H2A(+21+45) or DNM2 H2A(+23+47).

35. The antisense oligomer of any one of claims 1-3, 7, 9, 12-13, or 32, wherein the target region is DNM2 H2A(+23+47) or DNM2 H2A(+27+51).

36. The antisense oligomer of any one of claims 1-3, 7, 9, 14-15, or 32, wherein the target region is DNM2 H2A(+46+70) or DNM2 H2A(+48+72).

37. The antisense oligomer of any one of claims 1, 4-5, 7, 9, 16-17, or 32, wherein the target region is DNM2 H2D(+13-12), DNM2 H2D(+12-13), DNM2 H2D(+11-14), DNM2 H2D(+10-15), DNM2 H2D(+9-16), DNM2 H2D(+8-17), DNM2 H2D(+7-18), DNM2H2D(+6-19), DNM2 H2D(+5-20), DNM2 H2D(+4-21), DNM2 H2D(+3-22), DNM2 H2D(+2-23), or DNM2 H2D(+1-24).

38. The antisense oligomer of any one of claims 1, 4-5, 7, 9, 16-19, 32, or 37, wherein the target region is DNM2 H2D (+13-12), DNM2 H2D(+12-13), or DNM2 H2D(+11-14).

39. The antisense oligomer of any one of claims 1, 4-5, 7, 9, 16-17, 20-21, 32, or 37, wherein the target region is DNM2 H2D(+10-15), DNM2 H2D(+9-16), DNM2 H2D(+8-17), DNM2 H2D(+7-18), or DNM2 H2D(+6-19).

40. The antisense oligomer of any one of claims 1, 4-5, 7, 9, 16-17, 20-23, 32, 37, or 39, wherein the target region is DNM2 H2D(+9-16), DNM2 H2D(+8-17), or DNM2 H2D(+7- 18).

41. The antisense oligomer of any one of claims 1, 4-5, 7, 9, 16-17, 20-23, 32, 35, 37, or 39- 40, wherein the target region is DNM2 H2D(+8-17).

42. The antisense oligomer of any one of claims 1, 4-5, 7, 9, 16-17, 24-25, 32, or 37, wherein the target region is DNM2 H2D(+6-19), DNM2 H2D(+5-20), DNM2 H2D(+4-21), DNM2 H2D(+3-22), DNM2 H2D(+2-23).

43. The antisense oligomer of any one of claims 1, 4-5, 7, 9, 16-17, 24-27, 32, 37, or 42, wherein the target region is DNM2 H2D(+4-21), DNM2 H2D(+3-22), or DNM2 H2D(+2- 23).

44. The antisense oligomer of any one of claims 1, 4-5, 7, 9, 16-17, 24-27, 32, 37, or 42-43, wherein the target region is DNM2 H2D(+3-22).

45. The antisense oligomer of any one of claims 1, 6-7, 9, 28-29, or 32, wherein the target region is DNM2 H2D(-1-25), DNM2 H2D(-2-26), DNM2 H2D(-3-27), DNM2 H2D(-4-28), DNM2 H2D(-5-29), or DNM2 H2D(-6-30).

46. The antisense oligomer of any one of claims 1, 6-7, 9, 28-32, or 45, wherein the target region is DNM2 H2D(-1-25), DNM2 H2D(-2-26), DNM2 H2D(-3-27), DNM2 H2D(-4-28), or DNM2 H2D(-5-29).

47. The antisense oligomer of any one of claims 1, 4-5, 7, 9, or 32, wherein the target region of the human DNM2 gene pre-mRNA is DNM2 H2A (-10+15).

48. The antisense oligomer of any one of claims 1, 4-5, or 7, 9, or 32, wherein the target region of the human DNM2 gene pre-mRNA is DNM2 H2A(-7+17).

49. The antisense oligomer of any one of claims 1-3, 7, 9, or 32, wherein the target region of the human DNM2 gene pre-mRNA is DNM2 H2A(+3+27).

50. The antisense oligomer of any one of claims 1-3, 7, 9, or 32, wherein the target region of the human DNM2 gene pre-mRNA is DNM2 H2A(+15+37).

51. The antisense oligomer of any one of claims 1-3, 7, 9, or 32, wherein the target region of the human DNM2 gene pre-mRNA is DNM2 H2A(+37+61).

52. The antisense oligomer of any one of claims 1, 4-5, 7, 9, or 32, wherein the target region of the human DNM2 gene pre-mRNA is DNM2 H2D(+20-5).

53. The antisense oligomer of any one of claims 1-32, wherein the targeting sequence is selected from SEQ ID NOs: 67-96.

54. The antisense oligomer of any one of claims 1, 7, or 32-33, wherein the targeting sequence is selected from SEQ ID NOs: 78-96.

55. The antisense oligomer of any one of claims 1-3, 7, 9-11, 32, or 34, wherein the targeting sequence is selected from SEQ ID NOs: 71-72.

56. The antisense oligomer of any one of claims 1-3, 7, 9, 12-13, 32, or 35, wherein the targeting sequence is selected from SEQ ID NOs: 72-73.

57. The antisense oligomer of any one of claims 1-3, 7, 9, 14-15, 32, or 36, wherein the targeting sequence is selected from SEQ ID NOs: 75-76.

58. The antisense oligomer of any one of claims 1, 4-5, 7, 9, 16-17, 32, or 37, wherein the targeting sequence is selected from SEQ ID NOs: 78-90.

59. The antisense oligomer of any one of claims 1, 4-5, 7, 9, 16-19, 32, or 37-38, wherein the targeting sequence is selected from SEQ ID NOs: 78-80.

60. The antisense oligomer of any one of claims 1, 4-5, 7, 9, 16-17, 20-21, 32, 37, or 39, wherein the targeting sequence is selected from SEQ ID NOs: 81-85.

61. The antisense oligomer of any one of claims 1, 4-5, 7, 9, 16-17, 20-23, 32, 37, or 39-40, wherein the targeting sequence is selected from SEQ ID NOs: 82-84.

62. The antisense oligomer of any one of claims 1, 4-5, 7, 9, 16-17, 20-23, 32, 35, 37, or 39- 41, wherein the targeting sequence is SEQ ID NO:

83.

63. The antisense oligomer of any one of claims 1, 4-5, 7, 9, 16-17, 24-25, 32, 37, or 42, wherein the targeting sequence is selected from SEQ ID NOs: 85-89.

64. The antisense oligomer of any one of claims 1, 4-5, 7, 9, 16-17, 24-27, 32, 37, or 42-43, wherein the targeting sequence is selected from SEQ ID NOs: 87-89.

65. The antisense oligomer of any one of claims 1, 4-5, 7, 9, 16-17, 24-27, 32, 37, or 42-44, wherein the targeting sequence is SEQ ID NO:

88.

66. The antisense oligomer of any one of claims 1, 6-7, 9, 28-29, 32, or 45, wherein the targeting sequence is selected from SEQ ID NOs: 91-96.

67. The antisense oligomer of any one of claims 1, 6-7, 9, 28-32, or 45-46, wherein the targeting sequence is selected from SEQ ID NOs: 91-95.

68. The antisense oligomer of any one of claims 1, 4-5, 7, 9, 32, or 47, wherein the targeting sequence is SEQ ID NO:

67.

69. The antisense oligomer of any one of claims 1, 4-5, or 7, 9, 32, or 48, wherein the targeting sequence is SEQ ID NO:

68.

70. The antisense oligomer of any one of claims 1-3, 7, 9, 32, or 49, wherein the targeting sequence is SEQ ID NO:

69.

71. The antisense oligomer of any one of claims 1-3, 7, 9, 32, or 50, wherein the targeting sequence is SEQ ID NO:

70.

72. The antisense oligomer of any one of claims 1-3, 7, 9, 32, or 51, wherein the targeting sequence is SEQ ID NO:

74.

73. The antisense oligomer of any one of claims 1, 4-5, 7, 9, 32, or 52, wherein the targeting sequence is SEQ ID NO:

77.

74. The antisense oligomer of any one of claims 1-5, wherein the target region is within the exon internal region of exon 9 (SEQ ID NO: 6), the intron 8 / exon 9 junction, or the exon 9 / intron 9 junction of the human DNM2 gene pre-mRNA.

75. The antisense oligomer of any one of claims 1-3 or 74, wherein the target region of the human DNM2 gene pre-mRNA is within the 36thnucleotide to the 61stnucleotide of exon 9 measured from the 5′ end of exon 9 (SEQ ID NO: 6).

76. The antisense oligomer of claim 75, wherein the target region is a region within SEQ ID NO:

24.

77. The antisense oligomer of any one of claims 1-3 or 74, wherein the target region of the human DNM2 gene pre-mRNA is within the 42ndnucleotide to the 68thnucleotide of exon 9 measured from the 5′ end of exon 9 (SEQ ID NO: 6).

78. The antisense oligomer of claim 77, wherein the target region is a region within SEQ ID NO:

25.

79. The antisense oligomer of any one of claims 1-3, 74, or 77-78, wherein the target region of the human DNM2 gene pre-mRNA is within the 43rdnucleotide to the 68thnucleotide of exon 9 measured from the 5′ end of exon 9 (SEQ ID NO: 6).

80. The antisense oligomer of claim 79, wherein the target region is a region within SEQ ID NO:

26.

81. The antisense oligomer of any one of claims 1, 4-5, or 74, wherein the target region of the human DNM2 gene pre-mRNA is within the 24thnucleotide of exon 9 measured from the 3′ end of exon 9 (SEQ ID NO: 6) to the 15thnucleotide of intron 9 measured from the 3′ end of exon 9.

82. The antisense oligomer of claim 81, wherein the target region is a region within SEQ ID NO:

27.

83. The antisense oligomer of any one of claims 1, 4-5, 74, or 81-82, wherein the target region of the human DNM2 gene pre-mRNA is within the 24thnucleotide of exon 9 measured from the 3′ end of exon 9 (SEQ ID NO: 6) to the 5thnucleotide of intron 9 measured from the 3′ end of exon 9.

84. The antisense oligomer of claim 83, wherein the target region is a region within SEQ ID NO:

28.

85. The antisense oligomer of any one of claims 1, 4-5, 74, or 81-82, wherein the target region of the human DNM2 gene pre-mRNA is within the 19thnucleotide of exon 9 measured from the 3′ end of exon 9 (SEQ ID NO: 6) to the 10thnucleotide of intron 9 measured from the 3′ end of exon 9.

86. The antisense oligomer of claim 85, wherein the target region is a region within SEQ ID NO:

29.

87. The antisense oligomer of any one of claims 1, 4-5, 74, or 81-82, wherein the target region of the human DNM2 gene pre-mRNA is within the 14thnucleotide of exon 9 measured from the 3′ end of exon 9 (SEQ ID NO: 6) to the 15thnucleotide of intron 9 measured from the 3′ end of exon 9.

88. The antisense oligomer of claim 87, wherein the target region is a region within SEQ ID NO:

30.

89. The antisense oligomer of any one of claims 1, 4-5, or 74, wherein the target region of the human DNM2 gene pre-mRNA is within the 9thnucleotide of exon 9 measured from the 3′ end of exon 9 (SEQ ID NO: 6) to the 22ndnucleotide of intron 9 measured from the 3′ end of exon 9.

90. The antisense oligomer of claim 89, wherein the target region is a region within SEQ ID NO:

31.

91. The antisense oligomer of any one of claims 1, 4-5, 74, or 89-90, wherein the target region of the human DNM2 gene pre-mRNA is within the 9thnucleotide of exon 9 measured from the 3′ end of exon 9 (SEQ ID NO: 6) to the 20thnucleotide of intron 9 measured from the 3′ end of exon 9.

92. The antisense oligomer of claim 91, wherein the target region is a region within SEQ ID NO:

32.

93. The antisense oligomer of any one of claims 1, 4-5, 74, or 89-92, wherein the target region of the human DNM2 gene pre-mRNA is within the 9thnucleotide of exon 9measured from the 3′ end of exon 9 (SEQ ID NO: 6) to the 18thnucleotide of intron 9 measured from the 3′ end of exon 9.

94. The antisense oligomer of claim 93, wherein the target region is a region within SEQ ID NO:

33.

95. The antisense oligomer of any one of claims 1, 4-5, 74, or 89-90, wherein the target region of the human DNM2 gene pre-mRNA is within the 8thnucleotide of exon 9 measured from the 3′ end of exon 9 (SEQ ID NO: 6) to the 21stnucleotide of intron 9 measured from the 3′ end of exon 9.

96. The antisense oligomer of claim 95, wherein the target region is a region within SEQ ID NO:

34.

97. The antisense oligomer of any one of claims 1, 4-5, 74, or 89-90, wherein the target region of the human DNM2 gene pre-mRNA is within the 6thnucleotide of exon 9 measured from the 3′ end of exon 9 (SEQ ID NO: 6) to the 22ndnucleotide of intron 9 measured from the 3′ end of exon 9.

98. The antisense oligomer of claim 97, wherein the target region is a region within SEQ ID NO:

35.

99. The antisense oligomer of any one of claims 1-5, 7, or 74-98, wherein the target region of the human DNM2 gene pre-mRNA is DNM2 H9A(-12+13), DNM2 H9A(-5+20), DNM2 H9A(+1+25),DNM2 H9A(+6+30), DNM2 H9A(+16+40), DNM2 H9A(+25+49), DNM2 H9A(+36+60), DNM2 H9A(+37+61), DNM2 H9A(+42+66), DNM2 H9A(+43+62), DNM2 H9A(+43+63), DNM2 H9A(+43+64), DNM2 H9A(+43+65), DNM2 H9A(+43+66), DNM2 H9A(+43+67), DNM2 H9A(+44+67), DNM2 H9A(+44+68), DNM2 H9A(+45+67), DNM2 H9A (+46+67), DNM2 H9A(+47+67), DNM2 H9A(+48+67), DNM2 H9D(+24-1), DNM2 H9D(+23-2), DNM2 H9D(+22-3), DNM2 H9D(+21-4), DNM2 H9D(+20-5), DNM2 H9D(+19-6), DNM2 H9D (+18-7), DNM2 H9D(+17-8), DNM2 H9D(+16-9), DNM2 H9D(+15-10), DNM2 H9D(+14-11), DNM2 H9D(+13-12), DNM2 H9D(+12-13), DNM2 H9D(+11-14), DNM2 H9D(+10-15), DNM2 H9D(+9-16), DNM2 H9D(+8-12), DNM2 H9D(+8-13), DNM2 H9D(+8-14), DNM2 H9D(+8-15), DNM2 H9D(+8-17), DNM2 H9D(+7-18), DNM2 H9D(+7-17), DNM2 H9D(+6-19), DNM2 H9D(+6-17), DNM2 H9D(+5-17), DNM2 H9D(+5-20), DNM2 H9D(+4-17), DNM2 H9D(+4-21), DNM2 H9D(+3-17), or DNM2 H9D(+3-22).

100. The antisense oligomer of claim 99, wherein the target region of the human DNM2 gene pre-mRNA is DNM2 H9A(+16+40), DNM2 H9A(+25+49), DNM2 H9A(+36+60), DNM2 H9A(+37+61), DNM2 H9A(+43+67), DNM2 H9A(+42+66), DNM2 H9A(+44+68), DNM2 H9D(+24-1), DNM2 H9D(+23-2), DNM2 H9D(+22-3), DNM2 H9D(+21-4), DNM2H9D(+20-5), DNM2 H9D(+19-6), DNM2 H9D (+18-7), DNM2 H9D(+17-8), DNM2 H9D(+16-9), DNM2 H9D(+15-10), DNM2 H9D(+14-11), DNM2 H9D(+13-12), DNM2 H9D(+12-13), DNM2 H9D(+11-14), DNM2 H9D(+10-15), DNM2 H9D(+9-16), DNM2 H9D(+8-17), DNM2 H9D(+7-18), DNM2 H9D(+6-19), DNM2 H9D(+5-20), DNM2 H9D(+4-21), or DNM2 H9D(+3-22).

101. The antisense oligomer of any one of claims 1-5, 7, 74-76, or 99, wherein the target region of the human DNM2 gene pre-mRNA is DNM2 H9A(+36+60) or DNM2 H9A(+37+61).

102. The antisense oligomer of any one of claims 1-3, 7, 74, 77-78, or 99, wherein the target region of the human DNM2 gene pre-mRNA is DNM2 H9A(+42+66), DNM2 H9A(+43+62), DNM2 H9A(+43+63), DNM2 H9A(+43+64), DNM2 H9A(+43+65), DNM2 H9A(+43+66), DNM2 H9A(+43+67), DNM2 H9A(+44+67), DNM2 H9A(+44+68), DNM2 H9A(+45+67), DNM2 H9A (+46+67), DNM2 H9A(+47+67), or DNM2 H9A(+48+67).

103. The antisense oligomer of any one of claims 1-3, 7, 74, 77-80, 99, or 102, wherein the target region of the human DNM2 gene pre-mRNA is DNM2 H9A(+43+62), DNM2 H9A(+43+63), DNM2 H9A(+43+64), DNM2 H9A(+43+65), DNM2 H9A(+43+66), DNM2 H9A(+43+67), DNM2 H9A(+44+67), or DNM2 H9A(+44+68).

104. The antisense oligomer of any one of claims 1-3, 7, 74, 77-80, 99, or 102-103, wherein the target region of the human DNM2 gene pre-mRNA is DNM2 H9A(+43+67).

105. The antisense oligomer of any one of claims 1, 4-5, 7, 74, 81-82, or 99, wherein the target region of the human DNM2 gene pre-mRNA is DNM2 H9D(+24-1), DNM2 H9D(+23-2), DNM2 H9D(+22-3), DNM2 H9D(+21-4), DNM2 H9D(+20-5), DNM2 H9D(+19-6), DNM2 H9D (+18-7), DNM2 H9D(+17-8), DNM2 H9D(+16-9), DNM2 H9D(+15-10), DNM2 H9D(+14-11), DNM2 H9D(+13-12), DNM2 H9D(+12-13), DNM2 H9D(+11-14), or DNM2 H9D(+10-15).

106. The antisense oligomer of any one of claims 1, 4-5, 7, 74, 81-84, 99, or 105, wherein the target region of the human DNM2 gene pre-mRNA is DNM2 H9D(+24-1), DNM2 H9D(+23-2), DNM2 H9D(+22-3), DNM2 H9D(+21-4), or DNM2 H9D(+20-5).

107. The antisense oligomer of any one of claims 1, 4-5, 7, 74, 81-82, 85-86, or 99, wherein the target region of the human DNM2 gene pre-mRNA is DNM2 H9D(+19-6), DNM2 H9D (+18-7), DNM2 H9D(+17-8), DNM2 H9D(+16-9), or DNM2 H9D(+15-10).

108. The antisense oligomer of any one of claims 1, 4-5, 7, 74, 81-82, 87-88, or 99, wherein the target region of the human DNM2 gene pre-mRNA is DNM2 H9D(+14-11), DNM2 H9D(+13-12), DNM2 H9D(+12-13), DNM2 H9D(+11-14), or DNM2 H9D(+10-15).

109. The antisense oligomer of any one of claims 1, 4-5, 7, 74, 89-90, or 99, wherein the target region of the human DNM2 gene pre-mRNA is DNM2 H9D(+9-16), DNM2 H9D(+8-12), DNM2 H9D(+8-13), DNM2 H9D(+8-14), DNM2 H9D(+8-15), DNM2 H9D(+8-17), DNM2 H9D(+7-18), DNM2 H9D(+7-17), DNM2 H9D(+6-19), DNM2 H9D(+6-17), DNM2 H9D(+5-17), DNM2 H9D(+5-20), DNM2 H9D(+4-17), DNM2 H9D(+4-21), DNM2 H9D(+3-17), or DNM2 H9D(+3-22).

110. The antisense oligomer of any one of claims 1, 4-5, 7, 74, 89-92, 99, or 109, wherein the target region of the human DNM2 gene pre-mRNA is DNM2 H9D(+9-16), DNM2 H9D(+8-12), DNM2 H9D(+8-13), DNM2 H9D(+8-14), DNM2 H9D(+8-15), DNM2 H9D(+8-17), DNM2 H9D(+7-18), DNM2 H9D(+7-17), DNM2 H9D(+6-19), DNM2 H9D(+6-17), DNM2 H9D(+5-17), or DNM2 H9D(+5-20).

111. The antisense oligomer of any one of claims 1, 4-5, 7, 74, 89-94, 99, or 109-110, wherein the target region of the human DNM2 gene pre-mRNA is DNM2 H9D(+9-16), DNM2 H9D(+8-12), DNM2 H9D(+8-13), DNM2 H9D(+8-14), DNM2 H9D(+8-15), DNM2 H9D(+8-17), or DNM2 H9D(+7-18).

112. The antisense oligomer of any one of claims 1, 4-5, 7, 74, 89-90, 95-96, or 99, wherein the target region of the human DNM2 gene pre-mRNA is DNM2 H9D(+8-17), DNM2 H9D(+7-18), DNM2 H9D(+7-17), DNM2 H9D(+6-19), DNM2 H9D(+6-17), DNM2 H9D(+5-17), DNM2 H9D(+5-20), DNM2 H9D(+4-17), or DNM2 H9D(+4-21).

113. The antisense oligomer of any one of claims 1, 4-5, 7, 74, 89-96, 99, or 109-112, wherein the target region of the human DNM2 gene pre-mRNA is DNM2 H9D(+8-17).

114. The antisense oligomer of any one of claims 1, 4-5, 7, 74, 89-90, 97-99, or 109, wherein the target region of the human DNM2 gene pre-mRNA is DNM2 H9D(+6-19), DNM2 H9D(+6-17), DNM2 H9D(+5-17), DNM2 H9D(+5-20), DNM2 H9D(+4-17), DNM2 H9D(+4-21), DNM2 H9D(+3-17), or DNM2 H9D(+3-22).

115. The antisense oligomer of any one of claims 1, 4-5, 7, 74, or 99, wherein the target region of the human DNM2 gene pre-mRNA is DNM2 H9A(-12+13).

116. The antisense oligomer of any one of claims 1, 4-5, 7, 74, or 99, wherein the target region of the human DNM2 gene pre-mRNA is DNM2 H9A(-5+20).

117. The antisense oligomer of any one of claims 1-3, 7, 74, or 99, wherein the target region of the human DNM2 gene pre-mRNA is DNM2 H9A(+1+25).

118. The antisense oligomer of any one of claims 1-3, 7, 74, or 99, wherein the target region of the human DNM2 gene pre-mRNA is DNM2 H9A(+6+30).

119. The antisense oligomer of any one of claims 1-3, 7, 74, or 99, wherein the target region of the human DNM2 gene pre-mRNA is DNM2 H9A(+16+40).

120. The antisense oligomer of any one of claims 1-3, 7, 74, or 99, wherein the target region of the human DNM2 gene pre-mRNA is DNM2 H9A(+25+49).

121. The antisense oligomer of any one of claims 1-5, 7, or 74-99, wherein the targeting sequence is selected from SEQ ID NOs: 158-209.

122. The antisense oligomer of any one of claims 1, 7, or 99-100, wherein the targeting sequence is selected from SEQ ID NOs: 162-166, 172, 174, 179-194, 199-200, 205, 207, and 209.

123. The antisense oligomer of any one of claims 1-5, 7, 74-76, 99, or 101, wherein the targeting sequence is selected from SEQ ID NOs: 164-165.

124. The antisense oligomer of any one of claims 1-3, 7, 74, 77-78, 99, or 102, wherein the targeting sequence is selected from SEQ ID NOs: 166-178.

125. The antisense oligomer of any one of claims 1-3, 7, 74, 77-80, 99, or 102-103, wherein the targeting sequence is selected from SEQ ID NOs: 167-174.

126. The antisense oligomer of any one of claims 1-3, 7, 74, 77-80, 99, or 102-104, wherein the targeting sequence is SEQ ID NO:

172.

127. The antisense oligomer of any one of claims 1, 4-5, 7, 74, 81-82, 99, or 105, wherein the targeting sequence is selected from SEQ ID NOs: 179-193.

128. The antisense oligomer of any one of claims 1, 4-5, 7, 74, 81-84, 99, or 105-106, wherein the targeting sequence is selected from SEQ ID NOs: 179-183.

129. The antisense oligomer of any one of claims 1, 4-5, 7, 74, 81-82, 85-86, 99, or 107, wherein the targeting sequence is selected from SEQ ID NOs: 184-188.

130. The antisense oligomer of any one of claims 1, 4-5, 7, 74, 81-82, 87-88, 99, or 108, wherein the targeting sequence is selected from SEQ ID NOs: 189-193.

131. The antisense oligomer of any one of claims 1, 4-5, 7, 74, 89-90, 99, or 109, wherein the targeting sequence is selected from SEQ ID NOs: 194-209.

132. The antisense oligomer of any one of claims 1, 4-5, 7, 74, 89-92, 99, or 109-110, wherein the targeting sequence is selected from SEQ ID NOs: 194-205.

133. The antisense oligomer of any one of claims 1, 4-5, 7, 74, 89-94, 99, or 109-111, wherein the targeting sequence is selected from SEQ ID NOs: 194-200.

134. The antisense oligomer of any one of claims 1, 4-5, 7, 74, 89-90, 95-96, 99, or 112, wherein the targeting sequence is selected from SEQ ID NOs: 199-207.

135. The antisense oligomer of any one of claims 1, 4-5, 7, 74, 89-96, 99, or 109-113, wherein the targeting sequence is SEQ ID NO:

199.

136. The antisense oligomer of any one of claims 1, 4-5, 7, 74, 89-90, 97-99, 109, or 114, wherein the targeting sequence is selected from SEQ ID NOs: 202-209.

137. The antisense oligomer of any one of claims 1, 4-5, 7, 74, 99, or 115, wherein the targeting sequence is SEQ ID NO:

158.

138. The antisense oligomer of any one of claims 1, 4-5, 7, 74, 99, or 116, wherein the targeting sequence is SEQ ID NO:

159.

139. The antisense oligomer of any one of claims 1-3, 7, 74, 99, or 117, wherein the targeting sequence is SEQ ID NO:

160.

140. The antisense oligomer of any one of claims 1-3, 7, 74, 99, or 118, wherein the targeting sequence is SEQ ID NO:

161.

141. The antisense oligomer of any one of claims 1-3, 7, 74, 99, or 119, wherein the targeting sequence is SEQ ID NO:

162.

142. The antisense oligomer of any one of claims 1-3, 7, 74, 99, or 120, wherein the targeting sequence is SEQ ID NO:

163.

143. The antisense oligomer of any one of claims 1-5, wherein the target region is within the exon internal region of exon 12 (SEQ ID NO: 7), the intron 11 / exon 12 junction, or the exon 12 / intron 12 junction of the human DNM2 gene pre-mRNA.

144. The antisense oligomer of any one of claims 1-3 or 143, wherein the target region of the human DNM2 gene pre-mRNA is within the 4thnucleotide to the 31stnucleotide measured of exon 12 from the 5′ end of exon 12 (SEQ ID NO: 7).

145. The antisense oligomer of claim 144, wherein the target region is a region within SEQ ID NO:

36.

146. The antisense oligomer of any one of claims 1-3 or 143, wherein the target region of the human DNM2 gene pre-mRNA is within the 10thnucleotide to the 44thnucleotide of exon 12 measured from the 5′ end of exon 12 (SEQ ID NO: 7).

147. The antisense oligomer of claim 146, wherein the target region is a region within SEQ ID NO:

37.

148. The antisense oligomer of any one of claims 1-3, 143, or 146-147, wherein the target region of the human DNM2 gene pre-mRNA is within the 10thnucleotide to the 38thnucleotide of exon 12 measured from the 5′ end of exon 12 (SEQ ID NO: 7).

149. The antisense oligomer of claim 148, wherein the target region is a region within SEQ ID NO:

38.

150. The antisense oligomer of any one of claims 1-3, 143, or 146-147, wherein the target region of the human DNM2 gene pre-mRNA is within the 16thnucleotide to the 44thnucleotide of exon 12 measured from the 5′ end of exon 12 (SEQ ID NO: 7).

151. The antisense oligomer of claim 150, wherein the target region is a region within SEQ ID NO: 39.

152. The antisense oligomer of any one of claims 1-3, 143, or 146-151, wherein the target region of the human DNM2 gene pre-mRNA is within the 14thnucleotide to the 42ndnucleotide of exon 12 measured from the 5′ end of exon 12 (SEQ ID NO: 7).

153. The antisense oligomer of claim 152, wherein the target region is a region within SEQ ID NO:

40.

154. The antisense oligomer of any one of claims 1-3 or 143, wherein the target region of the human DNM2 gene pre-mRNA is within the 25thnucleotide to the 54thnucleotide of exon 12 measured from the 5′ end of exon 12 (SEQ ID NO: 7).

155. The antisense oligomer of claim 154, wherein the target region is a region within SEQ ID NO:

41.

156. The antisense oligomer of any one of claims 1-3, 143, or 154-155, wherein the target region of the human DNM2 gene pre-mRNA is within the 25thnucleotide to the 53rdnucleotide of exon 12 measured from the 5′ end of exon 12 (SEQ ID NO: 7).

157. The antisense oligomer of claim 156, wherein the target region is a region within SEQ ID NO:

42.

158. The antisense oligomer of any one of claims 1-3, 143, or 154-155, wherein the target region of the human DNM2 gene pre-mRNA is within the 26thnucleotide to the 54thnucleotide of exon 12 measured from the 5′ end of exon 12 (SEQ ID NO: 7).

159. The antisense oligomer of claim 158, wherein the target region is a region within SEQ ID NO:

43.

160. The antisense oligomer of any one of claims 1-3 or 143, wherein the target region of the human DNM2 gene pre-mRNA is within the 36thnucleotide to the 61stnucleotide of exon 12 measured from the 5′ end of exon 12 (SEQ ID NO: 7).

161. The antisense oligomer of claim 160, wherein the target region is a region within SEQ ID NO:

44.

162. The antisense oligomer of any one of claims 1, 4-5, or 143, wherein the target region of the human DNM2 gene pre-mRNA is within the 22ndnucleotide of exon 12 measured from the 3′ end of exon 12 (SEQ ID NO: 7) to the 5thnucleotide of intron 12 measured from the 3′ end of exon 12.

163. The antisense oligomer of claim 162, wherein the target region is a region within SEQ ID NO:

45.

164. The antisense oligomer of any one of claims 1-5, 7, or 143-163, wherein the target region of the human DNM2 gene pre-mRNA is DNM2 H12A(-13+12), DNM2 H12A(- 3+22), DNM2 H12A(+4+28), DNM2 H12A(+7+31), DNM2 H12A(+10+34), DNM2 H12A(+11+35), DNM2 H12A(+12+36), DNM2 H12A(+13+37), DNM2 H12A(+14+38),DNM2 H12A(+15+39), DNM2 H12A(+16+40), DNM2 H12A(+17+41), DNM2 H12A(+18+42), DNM2 H12A(+19+43), DNM2 H12A(+20+44), DNM2 H12A(+25+44), DNM2 H12A(+25+45), DNM2 H12A(+25+46), DNM2 H12A(+25+47), DNM2 H12A(+25+48), DNM2 H12A(+25+49), DNM2 H12A(+26+49), DNM2 H12A(+27+49), DNM2 H12A(+28+49), DNM2 H12A(+29+49), DNM2 H12A(+29+53), DNM2 H12A(+30+49), DNM2 H12A(+30+54), DNM2 H12A(+36+60), DNM2 H12A(+37+61), DNM2 H12A(+43+67), DNM2 H12D(+22-3), DNM2 H12D(+20-5), or DNM2 H12D(+15- 10).

165. The antisense oligomer of any one of claim 164, wherein the target region of the human DNM2 gene pre-mRNA is DNM2 H12A(-3+22), DNM2 H12A(+4+28), DNM2 H12A(+7+31), DNM2 H12A(+10+34), DNM2 H12A(+11+35), DNM2 H12A(+12+36), DNM2 H12A(+13+37), DNM2 H12A(+14+38), DNM2 H12A(+15+39), DNM2 H12A(+16+40), DNM2 H12A(+17+41), DNM2 H12A(+18+42), DNM2 H12A(+19+43), DNM2 H12A(+20+44), DNM2 H12A(+25+49), DNM2 H12A(+29+53), DNM2 H12A(+30+54), DNM2 H12A(+36+60), DNM2 H12A(+37+61), DNM2 H12A(+43+67), DNM2 H12D(+22-3), DNM2 H12D(+20-5), or DNM2 H12D(+15-10).

166. The antisense oligomer of any one of claims 1-3, 7, 143-145, or 164, wherein the target region is DNM2 H12A(+4+28) or DNM2 H12A(+7+31).

167. The antisense oligomer of any one of claims 1-3, 7, 143, 146-147, or 164, wherein the target region is DNM2 H12A(+10+34), DNM2 H12A(+11+35), DNM2 H12A(+12+36), DNM2 H12A(+13+37), DNM2 H12A(+14+38), DNM2 H12A(+15+39), DNM2 H12A(+16+40), DNM2 H12A(+17+41), DNM2 H12A(+18+42), DNM2 H12A(+19+43), DNM2 H12A(+20+44).

168. The antisense oligomer of any one of claims 1-3, 7, 143, 146-149, 164, or 167, wherein the target region is DNM2 H12A(+10+34), DNM2 H12A(+11+35), DNM2 H12A(+12+36), DNM2 H12A(+13+37), or DNM2 H12A(+14+38).

169. The antisense oligomer of any one of claims 1-3, 7, 143, 146-147, 150-151, 164, or 167, wherein the target region is DNM2 H12A(+16+40), DNM2 H12A(+17+41), DNM2 H12A(+18+42), DNM2 H12A(+19+43), or DNM2 H12A(+20+44).

170. The antisense oligomer of any one of claims 1-3, 7, 143, 146-153, 164, or 167-169, wherein the target region is DNM2 H12A(+14+38), DNM2 H12A(+15+39), DNM2 H12A(+16+40), DNM2 H12A(+17+41), or DNM2 H12A(+18+42).

171. The antisense oligomer of any one of claims 1-3, 7, 143, 154-155, or 164, wherein the target region is DNM2 H12A(+25+44), DNM2 H12A(+25+45), DNM2 H12A(+25+46), DNM2 H12A(+25+47), DNM2 H12A(+25+48), DNM2 H12A(+25+49), DNM2H12A(+26+49), DNM2 H12A(+27+49), DNM2 H12A(+28+49), DNM2 H12A(+29+49), DNM2 H12A(+29+53), DNM2 H12A(+30+49), or DNM2 H12A(+30+54).

172. The antisense oligomer of any one of claims 1-3, 7, 143, 154-157, 164, or 171, wherein the target region is DNM2 H12A(+25+44), DNM2 H12A(+25+45), DNM2 H12A(+25+46), DNM2 H12A(+25+47), DNM2 H12A(+25+48), DNM2 H12A(+25+49), DNM2 H12A(+26+49), DNM2 H12A(+27+49), DNM2 H12A(+28+49), DNM2 H12A(+29+49), or DNM2 H12A(+29+53).

173. The antisense oligomer of any one of claims 1-3, 7, 143, 154-155, 158-159, 164, or 171, wherein the target region is DNM2 H12A(+26+49), DNM2 H12A(+27+49), DNM2 H12A(+28+49), DNM2 H12A(+29+49), DNM2 H12A(+29+53), DNM2 H12A(+30+49), or DNM2 H12A(+30+54).

174. The antisense oligomer of any one of claims 1-3, 7, 143, 154-155, 158-159, 164, 171, or 173, wherein the target region is DNM2 H12A(+25+49).

175. The antisense oligomer of any one of claims 1-3, 7, 143, 160-161, or 164, wherein the target region is DNM2 H12A(+36+60) or DNM2 H12A(+37+61).

176. The antisense oligomer of any one of claims 1, 4-5, 7, 143, or 162-164, wherein the target region is DNM2 H12D(+22-3) or DNM2 H12D(+20-5).

177. The antisense oligomer of any one of claims 1, 4-5, 7, 143, or 164, wherein the target region is DNM2 H12A(-13+12).

178. The antisense oligomer of any one of claims 1, 4-5, 7, 143, or 164, wherein the target region is DNM2 H12A(-3+22).

179. The antisense oligomer of any one of claims 1-3, 7, 143, or 164, wherein the target region is DNM2 H12A(+43+67).

180. The antisense oligomer of any one of claims 1, 4-5, 7, 143, or 164, wherein the target region is DNM2 H12D(+15-10).

181. The antisense oligomer of any one of claims 1-5, 7, or 143-164, wherein the targeting sequence is selected from SEQ ID NOs: 210-243.

182. The antisense oligomer of any one of claims 1, 7, or 164-165, wherein the targeting sequence is selected from SEQ ID NOs: 211-224, 230, 235, 237-238, and 240-243.

183. The antisense oligomer of any one of claims 1-3, 7, 143-145, 164, or 166, wherein the targeting sequence is selected from SEQ ID NOs: 212-213.

184. The antisense oligomer of any one of claims 1-3, 7, 143, 146-147, 164, or 167, wherein the targeting sequence is selected from SEQ ID NOs: 214-224.

185. The antisense oligomer of any one of claims 1-3, 7, 143, 146-149, 164, or 167-168, wherein the targeting sequence is selected from SEQ ID NOs: 214-218.

186. The antisense oligomer of any one of claims 1-3, 7, 143, 146-147, 150-151, 164, or 169, wherein the targeting sequence is selected from SEQ ID NOs: 220-224.

187. The antisense oligomer of any one of claims 1-3, 7, 143, 146-153, 164, 167-170, wherein the targeting sequence is selected from SEQ ID NOs: 218-222.

188. The antisense oligomer of any one of claims 1-3, 7, 143, 154-155, 164, or 171, wherein the targeting sequence is selected from SEQ ID NOs: 225-237.

189. The antisense oligomer of any one of claims 1-3, 7, 143, 154-157, 164, or 171-172, wherein the targeting sequence is selected from SEQ ID NOs: 225-235.

190. The antisense oligomer of any one of claims 1-3, 7, 143, 154-155, 158-159, 164, or 173, wherein the targeting sequence is selected from SEQ ID NOs: 231-237.

191. The antisense oligomer of any one of claims 1-3, 7, 143, 154-155, 158-159, 164, or 174, wherein the targeting sequence is SEQ ID NO:

230.

192. The antisense oligomer of any one of claims 1-3, 7, 143, 160-161, 164, or 175, wherein the targeting sequence is selected from SEQ ID NOs: 238-239.

193. The antisense oligomer of any one of claims 1, 4-5, 7, 143, 162-164, or 176, wherein the targeting sequence is selected from SEQ ID NOs: 241-242.

194. The antisense oligomer of any one of claims 1, 4-5, 7, 143, 164, or 177, wherein the targeting sequence is SEQ ID NO:

210.

195. The antisense oligomer of any one of claims 1, 4-5, 7, 143, 164, or 178, wherein the targeting sequence is SEQ ID NO:

211.

196. The antisense oligomer of any one of claims 1-3, 7, 143, 164, or 179, wherein the targeting sequence is SEQ ID NO:

240.

197. The antisense oligomer of any one of claims 1, 4-5, 7, 143, 164, or 180, wherein the targeting sequence is SEQ ID NO:

243.

198. The antisense oligomer of any one of claims 1-6, wherein the target region is within the exon internal region of exon 13 (SEQ ID NO: 8), the intron 12 / exon 13 junction, the exon 13 / intron 13 junction, or the intron internal region of intron 12 (SEQ ID NO: 12).

199. The antisense oligomer of any one of claims 1, 4-6, or 198, wherein the target region of the human DNM2 gene pre-mRNA is within the 27thnucleotide of intron 12 measured from the 5′ end of exon 13 (SEQ ID NO: 8) to the 12thnucleotide of exon 13 measured from the 5′ end of exon 13.

200. The antisense oligomer of claim 199, wherein the target region is a region within SEQ ID NO:

46.

201. The antisense oligomer of any one of claims 1, 4-6, or 198-200, wherein the target region of the human DNM2 gene pre-mRNA is within the 27thnucleotide of intron 12measured from the 5′ end of exon 13 (SEQ ID NO: 8) to the 2ndnucleotide of exon 13 measured from the 5′ end of exon 13.

202. The antisense oligomer of claim 201, wherein the target region is a region within SEQ ID NO:

47.

203. The antisense oligomer of any one of claims 1, 4-6, or 198-200, wherein the target region of the human DNM2 gene pre-mRNA is within the 22ndnucleotide of intron 12 measured from the 5′ end of exon 13 (SEQ ID NO: 8) to the 7thnucleotide of exon 13 measured from the 5′ end of exon 13.

204. The antisense oligomer of claim 203, wherein the target region is a region within SEQ ID NO:

48.

205. The antisense oligomer of any one of claims 1, 4-6, or 198-200, wherein the target region of the human DNM2 gene pre-mRNA is within the 17thnucleotide of intron 12 measured from the 5′ end of exon 13 (SEQ ID NO: 8) to the 12thnucleotide of exon 13 measured from the 5′ end of exon 13.

206. The antisense oligomer of claim 205, wherein the target region is a region within SEQ ID NO:

49.

207. The antisense oligomer of any one of claims 1, 4-5, or 198, wherein the target region of the human DNM2 gene pre-mRNA is within the 11thnucleotide of intron 12 (SEQ ID NO: 12) measured from the 5′ end of exon 13 (SEQ ID NO: 8) to the 24thnucleotide of exon 13 measured from the 5′ end of exon 13.

208. The antisense oligomer of claim 207, wherein the target region is a region within SEQ ID NO:

50.

209. The antisense oligomer of any one of claims 1, 4-5, 198, or 207-208, wherein the target region of the human DNM2 gene pre-mRNA is within the 11thnucleotide of intron 12 measured from the 5′ end of exon 13 (SEQ ID NO: 8) to the 18thnucleotide of exon 13 measured from the 5′ end of exon 13.

210. The antisense oligomer of claim 209, wherein the target region is a region within SEQ ID NO:

51.

211. The antisense oligomer of any one of claims 1, 4-5, 198, or 207-208, wherein the target region of the human DNM2 gene pre-mRNA is within the 5thnucleotide of intron 12 measured from the 5′ end of exon 13 (SEQ ID NO: 8) to the 24thnucleotide exon 13 measured from the 5′ end of exon 13.

212. The antisense oligomer of claim 211, wherein the target region is a region within SEQ ID NO: 52.

213. The antisense oligomer of any one of claims 1, 4-5, 191, or 207-212, wherein the target region of the human DNM2 gene pre-mRNA is within the 8thnucleotide of intron 12 measured from the 5′ end of exon 13 (SEQ ID NO: 8) to the 21stnucleotide exon 13 measured from the 5′ end of exon 13.

214. The antisense oligomer of claim 213, wherein the target region is a region within SEQ ID NO:

53.

215. The antisense oligomer of any one of claims 1-3 or 198, wherein the target region of the human DNM2 gene pre-mRNA is within the 1stnucleotide to the 30thnucleotide of exon 13 measured from the 5′ end of exon 13 (SEQ ID NO: 8).

216. The antisense oligomer of claim 215, wherein the target region is a region within SEQ ID NO:

54.

217. The antisense oligomer of any one of claims 1-3, 198, or 215-216, wherein the target region of the human DNM2 gene pre-mRNA is within the 1stnucleotide to the 28thnucleotide of exon 13 measured from the 5′ end of exon 13 (SEQ ID NO: 8).

218. The antisense oligomer of claim 217, wherein the target region is a region within SEQ ID NO:

55.

219. The antisense oligomer of any one of claims 1-3, 198, or 215-216, wherein the target region of the human DNM2 gene pre-mRNA is within the 6thnucleotide to the 30thnucleotide of exon 13 measured from the 5′ end of exon 13 (SEQ ID NO: 8).

220. The antisense oligomer of claim 219, wherein the target region is a region within SEQ ID NO:

56.

221. The antisense oligomer of any one of claims 1-3, 198, or 215-220, wherein the target region of the human DNM2 gene pre-mRNA is within the 3rdnucleotide to the 30thnucleotide of exon 13 measured from the 5′ end of exon 13 (SEQ ID NO: 8).

222. The antisense oligomer of claim 221, wherein the target region is a region within SEQ ID NO:

57.

223. The antisense oligomer of any one of claims 1-7 or 198-221, wherein the target region of the human DNM2 gene pre-mRNA is DNM2 H13A(-27-3), DNM2 H13A(-26-2), DNM2 H13A(-25-1), DNM2 H13A(-24+1), DNM2 H13A(-23+2), DNM2 H13A(-22+3), DNM2 H13A(-21+4), DNM2 H13A(-20+5), DNM2 H13A(-19+6), DNM2 H13A(-18+7), DNM2 H13A(-17+8), DNM2 H13A(-16+9), DNM2 H13A(-15+10), DNM2 H13A(-14+11), DNM2 H13A(-13+12), DNM2 H13A(-11+14), DNM2 H13A(-10+15), DNM2 H13A(-9+16), DNM2 H13A(-8+17), DNM2 H13A(-7+18), DNM2 H13A(-6+19), DNM2 H13A(-5+20), DNM2 H13A(-4+21), DNM2 H13A(-3+22), DNM2 H13A(-2+23), DNM2 H13A(-1+24), DNM2 H13A(+1+25), DNM2 H13A(+2+25), DNM2 H13A(+3+27), DNM2 H13A(+4+23), DNM2H13A(+4+24), DNM2 H13A(+4+25), DNM2 H13A(+4+26), DNM2 H13A(+4+27), DNM2 H13A(+4+28), DNM2 H13A(+5+28), DNM2 H13A(+6+28), DNM2 H13A(+6+30), DNM2 H13A(+7+28), DNM2 H13A(+8+28), DNM2 H13A(+9+28), DNM2 H13A(+16+40), DNM2 H13D(+22-3), or DNM2 H13D(+7-18).

224. The antisense oligomer of claim 223, wherein the target region of the human DNM2 gene pre-mRNA is DNM2 H13A(-27-3), DNM2 H13A(-26-2), DNM2 H13A(-25-1), DNM2 H13A(-24+1), DNM2 H13A(-23+2), DNM2 H13A(-22+3), DNM2 H13A(-21+4), DNM2 H13A(-20+5), DNM2 H13A(-19+6), DNM2 H13A(-18+7), DNM2 H13A(-17+8), DNM2 H13A(-16+9), DNM2 H13A(-15+10), DNM2 H13A(-14+11), DNM2 H13A(-13+12), DNM2 H13A(-11+14), DNM2 H13A(-10+15), DNM2 H13A(-9+16), DNM2 H13A(-8+17), DNM2 H13A(-7+18), DNM2 H13A(-6+19), DNM2 H13A(-5+20), DNM2 H13A(-4+21), DNM2 H13A(-3+22), DNM2 H13A(-2+23), DNM2 H13A(-1+24), DNM2 H13A(+1+25), DNM2 H13A(+2+25), DNM2 H13A(+3+27), or DNM2 H13A(+4+28).

225. The antisense oligomer of any one of claims 1, 4-7, 198-200, or 223, wherein the target region of the human DNM2 gene pre-mRNA is DNM2 H13A(-27-3), DNM2 H13A(-26-2), DNM2 H13A(-25-1), DNM2 H13A(-24+1), DNM2 H13A(-23+2), DNM2 H13A(-22+3), DNM2 H13A(-21+4), DNM2 H13A(-20+5), DNM2 H13A(-19+6), DNM2 H13A(-18+7), DNM2 H13A(-17+8), DNM2 H13A(-16+9), DNM2 H13A(-15+10), DNM2 H13A(-14+11), or DNM2 H13A(-13+12).

226. The antisense oligomer of any one of claims 1, 4-7, 198-202, 223, or 225, wherein the target region of the human DNM2 gene pre-mRNA is DNM2 H13A(-27-3), DNM2 H13A(- 26-2), DNM2 H13A(-25-1), DNM2 H13A(-24+1), or DNM2 H13A(-23+2).

227. The antisense oligomer of any one of claims 1, 4-7, 198-200, 203-204, 223, or 225, wherein the target region of the human DNM2 gene pre-mRNA is DNM2 H13A(-22+3), DNM2 H13A(-21+4), DNM2 H13A(-20+5), DNM2 H13A(-19+6), or DNM2 H13A(-18+7).

228. The antisense oligomer of any one of claims 1, 4-7, 198-200, 205-206, 223, or 225, wherein the target region of the human DNM2 gene pre-mRNA is DNM2 H13A(-17+8), DNM2 H13A(-16+9), DNM2 H13A(-15+10), DNM2 H13A(-14+11), or DNM2 H13A(- 13+12).

229. The antisense oligomer of any one of claims 1, 4-7, 198, 207-208, or 223, wherein the target region of the human DNM2 gene pre-mRNA is DNM2 H13A(-11+14), DNM2 H13A(-10+15), DNM2 H13A(-9+16), DNM2 H13A(-8+17), DNM2 H13A(-7+18), DNM2 H13A(-6+19), DNM2 H13A(-5+20), DNM2 H13A(-4+21), DNM2 H13A(-3+22), DNM2 H13A(-2+23), or DNM2 H13A(-1+24).

230. The antisense oligomer of any one of claims 1, 4-5, 7, 198, 207-210, 223, or 229, wherein the target region of the human DNM2 gene pre-mRNA is DNM2 H13A(-11+14), DNM2 H13A(-10+15), DNM2 H13A(-9+16), DNM2 H13A(-8+17), or DNM2 H13A(-7+18).

231. The antisense oligomer of any one of claims 1, 4-5, 7, 198, 207-208, 211-212, 223, or 229, wherein the target region of the human DNM2 gene pre-mRNA is DNM2 H13A(- 5+20), DNM2 H13A(-4+21), DNM2 H13A(-3+22), DNM2 H13A(-2+23), or DNM2 H13A(- 1+24).

232. The antisense oligomer of any one of claims 1, 4-5, 7, 198, 207-214, 223, or 229-231, wherein the target region of the human DNM2 gene pre-mRNA is DNM2 H13A(-8+17), DNM2 H13A(-7+18), DNM2 H13A(-6+19), DNM2 H13A(-5+20), or DNM2 H13A(-4+21).

233. The antisense oligomer of any one of claims 1-3, 7, 198, 215-216, or 223, wherein the target region of the human DNM2 gene pre-mRNA is DNM2 H13A(+1+25), DNM2 H13A(+2+25), DNM2 H13A(+3+27), DNM2 H13A(+4+23), DNM2 H13A(+4+24), DNM2 H13A(+4+25), DNM2 H13A(+4+26), DNM2 H13A(+4+27), DNM2 H13A(+4+28), DNM2 H13A(+5+28), DNM2 H13A(+6+28), DNM2 H13A(+6+30), DNM2 H13A(+7+28), DNM2 H13A(+8+28), or DNM2 H13A(+9+28).

234. The antisense oligomer of any one of claims 1-3, 7, 198, 215-218, 223, or 233, wherein the target region of the human DNM2 gene pre-mRNA is DNM2 H13A(+1+25), DNM2 H13A(+2+25), DNM2 H13A(+3+27), DNM2 H13A(+4+23), DNM2 H13A(+4+24), DNM2 H13A(+4+25), DNM2 H13A(+4+26), DNM2 H13A(+4+27), DNM2 H13A(+4+28), or DNM2 H13A(+5+28).

235. The antisense oligomer of any one of claims 1-3, 7, 198, 215-216, 219-220, 223, or 233, wherein the target region of the human DNM2 gene pre-mRNA is DNM2 H13A(+6+28), DNM2 H13A(+6+30), DNM2 H13A(+7+28), DNM2 H13A(+8+28), or DNM2 H13A(+9+28).

236. The antisense oligomer of any one of claims 1-3, 7, 198, 215-223, or 228-235, wherein the target region of the human DNM2 gene pre-mRNA is DNM2 H13A(+3+27), DNM2 H13A(+4+23), DNM2 H13A(+4+24), DNM2 H13A(+4+25), DNM2 H13A(+4+26), DNM2 H13A(+4+27), DNM2 H13A(+4+28), DNM2 H13A(+5+28), DNM2 H13A(+6+28), or DNM2 H13A(+6+30).

237. The antisense oligomer of any one of claims 1-3, 7, 198, 215-223, or 228-236, wherein the target region of the human DNM2 gene pre-mRNA DNM2 H13A(+4+28).

238. The antisense oligomer of any one of claims 1-3, 7, 198, or 223, wherein the target region of the human DNM2 gene pre-mRNA is DNM2 H13A(+16+40).

239. The antisense oligomer of any one of claims 1, 4-5, 7, 198, or 223, wherein the target region of the human DNM2 gene pre-mRNA is DNM2 H13D(+22-3).

240. The antisense oligomer of any one of claims 1, 4-5, 7, 198, or 223, wherein the target region of the human DNM2 gene pre-mRNA is DNM2 H13D(+7-18).

241. The antisense oligomer of any one of claims 1-7, 198-221, or 223, wherein the targeting sequence is selected from SEQ ID NOs: 244-287.

242. The antisense oligomer of any one of claims 1, 7, or 223-224, wherein the targeting sequence is selected from SEQ ID NOs: 244-278.

243. The antisense oligomer of any one of claims 1, 4-7, 198-200, 223, or 225, wherein the targeting sequence is selected from SEQ ID NOs: 244-258.

244. The antisense oligomer of any one of claims 1, 4-7, 198-202, 223, or 225-226, wherein the targeting sequence is selected from SEQ ID NOs: 244-248.

245. The antisense oligomer of any one of claims 1, 4-7, 198-200, 203-204, 223, 225, or 227, wherein the targeting sequence is selected from SEQ ID NOs: 249-253.

246. The antisense oligomer of any one of claims 1, 4-7, 198-200, 205-206, 223, 225, or 228, wherein the targeting sequence is selected from SEQ ID NOs: 254-258.

247. The antisense oligomer of any one of claims 1, 4-7, 198, 207-208, 223, or 229, wherein the targeting sequence is selected from SEQ ID NOs: 259-269.

248. The antisense oligomer of any one of claims 1, 4-5, 7, 198, 207-210, 223, or 229-230, wherein the targeting sequence is selected from SEQ ID NOs: 259-263.

249. The antisense oligomer of any one of claims 1, 4-5, 7, 198, 207-208, 211-212, or 231, wherein the targeting sequence is selected from SEQ ID NOs: 265-269.

250. The antisense oligomer of any one of claims 1, 4-5, 7, 198, 207-214, 223, or 229-232, wherein the targeting sequence is selected from SEQ ID NOs: 262-265.

251. The antisense oligomer of any one of claims 1-3, 7, 198, 215-216, 223, or 233, wherein the targeting sequence is selected from SEQ ID NOs: 270-284.

252. The antisense oligomer of any one of claims 1-3, 7, 198, 215-218, 223, or 233-234, wherein the targeting sequence is selected from SEQ ID NOs: 270-279.

253. The antisense oligomer of any one of claims 1-3, 7, 198, 215-216, 219-220, 223, 233, or 235, wherein the targeting sequence is selected from SEQ ID NOs: 280-284.

254. The antisense oligomer of any one of claims 1-3, 7, 198, 215-223, or 228-236, wherein the targeting sequence is selected from SEQ ID NOs: 272-281.

255. The antisense oligomer of any one of claims 1-3, 7, 198, 215-223, or 228-237, wherein the targeting sequence is SEQ ID NO: 278.

256. The antisense oligomer of any one of claims 1-3, 7, 198, 223, or 238, wherein the targeting sequence is SEQ ID NO:

285.

257. The antisense oligomer of any one of claims 1, 4-5, 7, 198, 223, or 239, wherein the targeting sequence is SEQ ID NO:

286.

258. The antisense oligomer of any one of claims 1, 4-5, 7, 198, 223, or 240, wherein the targeting sequence is SEQ ID NO:

287.

259. The antisense oligomer of any one of claims 1-258, wherein the antisense oligomer is selected from a peptide nucleic acid, a locked nucleic acid, a phosphorodiamidate morpholino oligomer, a 2′-OMe phosphorothioate oligomer, or a combination thereof.

260. The antisense oligomer of any one of claims 1-259, wherein the antisense oligomer is a phosphorodiamidate morpholino oligomer.

261. The antisense oligomer of any one of claims 1-260, wherein the antisense oligomer is covalently linked to a delivery moiety selected from a cell-penetrating peptide, an antibody, a fragment of an antibody, and an antigen binding agent.

262. The antisense oligomer of any one of claims 1-261, wherein the antisense oligomer is covalently linked to a cell-penetrating peptide.

263. The antisense oligomer of claim 262, wherein the antisense oligomer is covalently linked to the cell-penetrating peptide by a linker selected from a direct bond, a glycine amino acid, a proline amino acid, glutamic acid amino acid, or an isoglutamine amino acid.

264. The antisense oligomer of claim 262 or 263, wherein the cell-penetrating peptide is selected from rTAT, Tat, R9F2, R5F2R4, R4, R5, R6, R7, R8, R9, (RXR)4, (RXR)5, (RXRRBR)2, (RAR)4F2, (RGR)4F2, and RBRBYLIQFRBRRBR, wherein A represents alanine, B represents β-alanine, F represents phenylalanine, G represents glycine, I represents isoleucine, L represents leucine, Q represents glutamine, R represents arginine, X represent 6-aminohexanoic acid, and Y represents tyrosine.

265. The antisense oligomer, or a pharmaceutically acceptable salt thereof, of any one of claims 1-258 having a structure of Formula (I):(I), wherein: A′ is selected from -OH,R5is -C(O)(O-alkyl)x-OH, wherein x is 3-10 and each alkyl group is, independently at each occurrence, C2-6-alkyl, or R5is selected from H, -C(O)C1-6-alkyl, trityl, monomethoxytrityl, -(C1-6-alkyl)-R6, -(C1-6- heteroalkyl)-R6, -C6-10-aryl-R6, 5-10 membered heteroaryl-R6, -C(O)O-(C1-6-alkyl)-R6, - C(O)O-aryl-R6, -C(O)O-(5-10 membered heteroaryl)-R6, and;R6is selected from -OH, -SH, and -NH2, or R6is O, S, or NH, each of which is covalently linked to a solid support; R9is C1-6alkyl; each R1is independently selected from -OH and -N(R3)(R4), wherein each R3and R4is, independently at each occurrence, -H or -C1-6-alkyl; each R2is independently selected from a naturally or non-naturally occurring nucleobase, which, when taken together, forms the targeting sequence; t is 11-28; E′ is selected from -H, -C1-6-alkyl, -C(O)C1-6-alkyl, benzoyl, stearoyl, trityl, monomethoxytrityl, dimethoxytrityl, trimethoxytrityl,; Q is -C(O)(CH2)6C(O)- or -C(O)(CH2)2S2(CH2)2C(O)-; R7is -(CH2)2OC(O)N(R8)2, wherein R8is -(CH2)6NHC(=NH)NH2; L is a linking amino acid, wherein L is covalently-linked by an amide bond to the C-terminus of J; J is a cell-penetrating peptide; and G is selected from -H, -C(O)C1-6-alkyl, benzoyl, and stearoyl, wherein G is covalently-linked to J.

266. The antisense oligomer of claim 265, wherein E′ is selected from -H, -C1-6-alkyl, -C(O)C1-6-alkyl, benzoyl, stearoyl, trityl, monomethoxytrityl, dimethoxytrityl, trimethoxytrityl, and.

267. The antisense oligomer of claim 265 or 266, wherein E′ is selected from -H, -C(O)CH3, benzoyl, stearoyl, trityl, 4-methoxytrityl, and.

268. The antisense oligomer of any one of claims 265-267, wherein A′ is selected from:.

269. The antisense oligomer of any one of claims 265-268, wherein at least one of the following is true:

270. The antisense oligomer of any one of claims 265-269, wherein A′ is selected from:E′ is.

271. The antisense oligomer of any one of claims 265-270, wherein A′ isE′ is selected from H, -C(O)CH3, trityl, 4-methoxytrityl, benzoyl, and stearoyl.

272. The antisense oligomer of any one of claims 265-271, wherein each R1is -N(CH3)2.

273. The antisense oligomer of any one of claims 265-272, wherein L is glycine, proline, or β- alanine.

274. The antisense oligomer of any one of claims 265-273, wherein L is glycine.

275. The antisense oligomer of any one of claims 265-273, wherein L is proline.

276. The antisense oligomer of any one of claims 265-273, wherein L is β-alanine.

277. The antisense oligomer of any one of claims 265-276, wherein J is selected from rTAT, Tat, R9F2, R5F2R4, R4, R5, R6, R7, R8, R9, (RXR)4, (RXR)5, (RXRRBR)2, (RAR)4F2, and (RGR)4F2, wherein A represents alanine, B represents β-alanine, F represents phenylalanine, G represents glycine, R represents arginine, and X represents 6- aminohexanoic acid.

278. The antisense oligomer of any one of claims 265-277, wherein G is selected from -H, - C(O)CH3, benzoyl, and stearoyl.

279. The antisense oligomer of any one of claims 265-278, wherein G is -H or -C(O)CH3.

280. The antisense oligomer of any one of claims 265-278, wherein G is -H.

281. The antisense oligomer of any one of claims 265-278, wherein G is -C(O)CH3.

282. The antisense oligomer of any one of claims 265-273, 276-279, or 281, wherein the antisense oligomer is of Formula (IA):,or a pharmaceutically acceptable salt thereof, wherein: A′ is a moiety selected from:

283. The antisense oligomer of any one of claims 265-270 or 272-282, wherein the antisense oligomer is of Formula (II):(II), or a pharmaceutically acceptable salt thereof.

284. The antisense oligomer of any one of claims 265-273, 276-279, or 281-283, wherein the antisense oligomer is of Formula (III):(III), or a pharmaceutically acceptable salt thereof, wherein n is 11-28.

285. The antisense oligomer of any one of claims 265-273, 276-279, or 281-284, or a pharmaceutically acceptable salt thereof, wherein the antisense oligomer is of Formula (IV):(IV), wherein n is 11-28.

286. The antisense oligomer of claim 284 or 285, or a pharmaceutically acceptable salt thereof, wherein each R2, taken together, forms a targeting sequence having SEQ ID NO:

83.

287. The antisense oligomer of claim 284 or 285, or a pharmaceutically acceptable salt thereof, wherein each R2, taken together, forms a targeting sequence having SEQ ID NO:

88.

288. The antisense oligomer of claim 284 or 285, or a pharmaceutically acceptable salt thereof, wherein each R2, taken together, forms a targeting sequence having SEQ ID NO:

172.

289. The antisense oligomer of claim 284 or 285, or a pharmaceutically acceptable salt thereof, wherein each R2, taken together, forms a targeting sequence having SEQ ID NO:

199.

290. The antisense oligomer of claim 284 or 285, or a pharmaceutically acceptable salt thereof, wherein each R2, taken together, forms a targeting sequence having SEQ ID NO:

230.

291. The antisense oligomer of claim 284 or 285, or a pharmaceutically acceptable salt thereof, wherein each R2, taken together, forms a targeting sequence having SEQ ID NO: 278.

292. An antisense oligomer selected from:,Ĭ šnd293. The antisense oligomer of claim 292 that is:.

294. The antisense oligomer of claim 292 that is:.

295. The antisense oligomer of claim 292 that is:.

296. The antisense oligomer of claim 292 that is:.

297. The antisense oligomer of claim 292 that is:.

298. The antisense oligomer of claim 292 that is:.

299. A pharmaceutical composition comprising the antisense oligomer of any one of claims 1- 298 and a pharmaceutically acceptable carrier.

300. A method of treating a disease or disorder, or sequelae thereof, associated with aberrant expression of dynamin 2 (DNM2) protein, comprising administering to a subject in need thereof a therapeutically effective amount of the oligomer of any one of claims 1-298 or the pharmaceutical composition of claim 299.

301. The method of claim 300, wherein the disease or disorder is a genetic neuromuscular disorder.

302. The method of claim 300 or 301, wherein the disease or disorder is caused by at least one mutation in a gene selected from DNM2 gene, MTM1 gene, BIN1 gene, RYR1 gene, TTN gene, SPEG gene, CACNA1S gene, MTMR14 gene, ZAK gene, and CCDC78 gene.

303. The method of any one of claims 300-302, wherein the disease or disorder is autosomal dominant, autosomal recessive, or X-linked.

304. The method of any one of claims 300-303, wherein the disease or disorder is a centronuclear myopathy (CNM).

305. The method of any one of claims 300-304, wherein the disease or disorder is myotubular myopathy (XLMTM or XLCNM), autosomal dominant congenital myopathy (ADCNM), autosomal recessive centronuclear myopathy (ARCNM), or Charcot-Marie-Tooth disease.