Methods and compositions for treatment of duchenne muscular dystrophy

Abstract

The technology described herein is directed to methods and compositions relating to chimeric polypeptides, e.g., for treatment of Duchenne muscular dystrophy.

Description

METHODS AND COMPOSITIONS FOR TREATMENT OF DUCHENNE MUSCULAR DYSTROPHYCROSS-REFERENCE TO RELATED APPLICATIONS

[0001] This application claims benefit under 35 U.S.C. § 119 of U.S. Provisional Application No. 63 / 658,100 filed June 10, 2024, the contents of which are incorporated herein by reference in their entirety.SEQUENCE LISTING

[0002] The instant application contains a Sequence Listing which has been submitted electronically in XML format and is hereby incorporated by reference in its entirety. Said XML copy, created on June 5, 2025, is named 046192-000119WOPT SL. xml and is 589.637 bytes in size.TECHNICAL FIELD

[0003] The technology described herein relates to methods and compositions for the treatment of Duchenne muscular dystrophy.BACKGROUND

[0004] Duchenne muscular dystrophy (DMD) is a genetic disease caused by mutation(s) of the dystrophin gene. The mutation(s) in the dystrophin gene result in lowered amounts of dystrophin protein. Dystrophin is necessary for muscle cell structure and function. In patients with DMD. the muscle tissue degrades and is replaced by connective tissue and fat over time.

[0005] DMD is one of the most common and severe of congenital myopathies. Current treatments such as glucocorticoid therapies may slow the progression of DMD, but do not address the underlying lack of dystrophin or muscle in jury and degradation.

[0006] In a normal, healthy patient, the utrophin protein is also expressed in muscles. The relatedness of utrophin and dystrophin led to an early hypothesis that utrophin itself, or reduced-sized versions of utrophin, could be used to treat DMD. This approach has not provided the therapeutic effects necessary' to provide clinical treatment of DMD.SUMMARY

[0007] As described herein, the invenotrs have found that combining portion of dystrophin and portions of utrophin to provide a novel chimeric protein provides significantly unproved therapeutic effects. Accordingly, the use of the chimeric proteins described herein (and nucleic acids and vectors, including AAV vectors encoding these proteins) are contemplated for use in the treatment of DMD.

[0008] In one aspect of any of the embodiments, described herein is a polypeptide comprising: a) a utrophin NT domain; b) a utrophin hinge 1 domain; c) a utrophin spectrin-like repeat (SLR) 1 domain; d) a utrophin spectrin-like repeat (SLR) 2 domain;c) a utrophin hinge 2 domain; f) a dystrophin SLR 20 domain; g) a dystrophin SLR 21 domain; h) a dystrophin SLR 22 domain; i) a dystrophin SLR 24 domain; j) a dystrophin hinge 4 domain; and k) a dystrophin cysteine rich (CR) domain.In some embodiments of any of the aspects, the polypeptide further comprises a utrophin spectrin-like repeat (SLR) 3 domain.

[0009] In one aspect of any of the embodiments, described herein is a polypeptide comprising: a utrophin NT domain; a utrophin hinge 1 domain; a utrophin spectrin-like repeat (SLR) 1 domain; a utrophin spectrin-like repeat (SLR) 2 domain; a utrophin hinge 2 domain; a dystrophin SLR 20 domain; a dystrophin SLR 21 domain; a dystrophin SLR 22 domain; a dystrophin SLR 24 domain; a dystrophin hinge 4 domain; and a dystrophin cysteine rich (CR) domain, a utrophin spectrin-like repeat (SLR) 3 domain.

[0010] In some embodiments of any of the aspects, the polypeptide further comprises a dystrophin SLR 23 domain. In some embodiments of any of the aspects, the polypeptide further comprises a utrophin spectrin-like repeat (SLR) 3 domain and a dystrophin SLR 23 domain. In some embodiments of any of the aspects, the polypeptide further comprises a dystroglycan binding domain. In some embodiments of any of the aspects, the polypeptide further comprises a domain selected from the group consisting of: a utrophin SLR 4 domain, a utrophin SLR 5 domain, a utrophin SLR 6 domain, a utrophin SLR 7 domain, a utrophin SLR 8 domain, a utrophin SLR 9 domain, a utrophin SLR 10 domain, a utrophin SLR 11 domain, a utrophin SLR 12 domain, a utrophin SLR 13 domain, a utrophin SLR 14 domain, a utrophin SLR 15 domain, a utrophin SLR 16 domain, a utrophin SLR 17 domain, and a utrophin hinge 3 domain.In some embodiments of any of the aspects, the polypeptide further comprises a domain selected from the group consisting of: a dystrophin SLR 4 domain, a dystrophin SLR 5 domain, a dystrophin SLR 6 domain, a dystrophin SLR 7 domain, a dystrophin SLR 8 domain, a dystrophin SLR 9 domain, a dystrophin SLR 10 domain, a dystrophin SLR 11 domain, a dystrophin SLR 12 domain, a dystrophinSLR 13 domain, a dystrophin SLR 14 domain, a dystrophin SLR 15 domain, a dystrophin SLR 16 domain, a dystrophin SLR 17 domain, dystrophin SLR 18 domain, and a dystrophin SLR 19 domain.

[0011] In some embodiments of any of the aspects, the polypeptide comprises, from N-tenninus to C -terminus: a) a utrophin NT domain; b) a utrophin hinge 1 domain; c) a utrophin spectrin-like repeat (SLR) 1 domain; d) a utrophin spectrin-like repeat (SLR) 2 domain; e) a utrophin hinge 2 domain; f) a dystrophin SLR 20 domain; g) a dystrophin SLR 21 domain; h) a dystrophin SLR 22 domain; i) a dystrophin SLR 24 domain; j) a dystrophin hinge 4 domain; k) a dystrophin cysteine rich (CR) domain; and l) a dystroglycan binding domain.In some embodiments of any of the aspects, the polypeptide comprises, comprises, from N-terminus to C-terminus: a) a utrophin NT domain; b) a utrophin hinge 1 domain; c) a utrophin spectrin-like repeat (SLR) 1 domain; d) a utrophin spectrin-like repeat (SLR) 2 domain; e) a utrophin spectrin-like repeat (SLR) 3 domain;1) a utrophin hinge 2 domain; g) a dystrophin SLR 20 domain; h) a dystrophin SLR 21 domain; i) a dystrophin SLR 22 domain; j) a dystrophin SLR 24 domain; k) a dystrophin hinge 4 domain; l) a dystrophin cysteine rich (CR) domain; and m) a dystroglycan binding domain.In some embodiments of any of the aspects, the polypeptide comprises, comprises, from N-terminus to C-tenninus: a) a utrophin NT domain; b) a utrophin hinge 1 domain; c) a utrophin spectrin-like repeat (SLR) 1 domain;d) a utrophin spcctrin-likc repeat (SLR) 2 domain; e) a utrophin hinge 2 domain; f) a dystrophin SLR 20 domain; g) a dystrophin SLR 21 domain; h) a dystrophin SLR 22 domain; i) a dystrophin SLR 23 domain; j) a dystrophin SLR 24 domain; k) a dystrophin hinge 4 domain; l) a dystrophin cysteine rich (CR) domain; and m) a dystrogly can binding domain.

[0012] In some embodiments of any of the aspects, a) the utrophin NT domain comprises the sequence of SEQ ID NO: 4 or 51 ; b) the utrophin hinge 1 domain comprises the sequence of SEQ ID NO: 5; c) the utrophin SLR 1 domain comprises the sequence of SEQ ID NO: 6; d) the utrophin SLR 2 domain comprises the sequence of SEQ ID NO: 7; e) the utrophin SLR 3 domain comprises the sequence of SEQ ID NO: 16;I) the utrophin hinge 2 domain comprises the sequence of SEQ ID NO: 8; g) the dystrophin SLR 20 domain comprises the sequence of SEQ ID NO: 9 or 500; h) the dystrophin SLR 21 domain comprises the sequence of SEQ ID NO: 10 or 501; i) the dystrophin SLR 22 domain comprises the sequence of SEQ ID NO: 11 or 502; j) the dystrophin SLR 23 domain comprises the sequence of SEQ ID NO: 12; k) the dystrophin SLR 24 domain comprises the sequence of SEQ ID NO: 13 or 503; l) the dystrophin hinge 4 domain comprises the sequence of SEQ ID NO: 14 or 504; m) the dystrophin CR domain comprises the sequence of SEQ ID NO: 15 or 505; n) the dystroglycan binding domain comprises the sequence of SEQ ID NO: 17 or 506 and / or o) sequences having at least 85%, at least 90%, at least 95% or greater sequence identity to any of the foregoing sequences.

[0013] In some embodiments of any of the aspects, the polypeptide comprises the sequence of one of SEQ ID NOs: 1-3. In some embodiments of any of the aspects, the polypeptide comprises the sequence of SEQ ID NO: 1. In some embodiments of any of the aspects, the polypeptide comprises the sequence of SEQ ID NO: 2. In some embodiments of any of the aspects, the polypeptide comprises the sequence of SEQ ID NO: 3.

[0014] In some embodiments of any of the aspects, the polypeptide does not comprise any of: a) a dystrophin SLR4 - SLR19 domain; b) a utrophin SLR4-SLR19 domain;c) a dystrophin hinge 3 domain; and d) a utrophin hinge 3 domain.In some embodiments of any of tire aspects, the polypeptide does not comprise any of: a) a dystrophin NT domain; b) a dystrophin hinge 1 domain; c) a dystrophin spectrin-like repeat (SLR) 1 domain; and d) a dystrophin spectrin-like repeat (SLR) 2 domain.In some embodiments of any of the aspects, the polypeptide does not comprise any of: a) a dystrophin NT domain; b) a dystrophin hinge 1 domain; c) a dystrophin spectrin-like repeat (SLR) 1 domain; d) a dystrophin spectrin-like repeat (SLR) 2 domain; and e) a dystrophin hinge 3 domain.In some embodiments of any of tire aspects, the polypeptide does not comprise any of: a) a dystrophin NT domain; b) a dystrophin hinge 1 domain; c) a dystrophin spectrin-like repeat (SLR) 1 domain; d) a dystrophin spectrin-like repeat (SLR) 2 domain; and e) a dystrophin hinge 2 domain.In some embodiments of any of the aspects, the polypeptide does not comprise any of: a) a dystrophin NT domain; and b) a dystrophin hinge 1 domain.In some embodiments of any of the aspects, the polypeptide does not comprise any of: a) a utrophin SLR 18 domain; b) a utrophin SLR 19 domain; c) a utrophin SLR 20 domain; d) a utrophin SLR 21 domain; e) a utrophin SLR 22 domain; f) a utrophin hinge 4 domain; and g) a utrophin CR domain.

[0015] In one aspect of any of the embodiments, described herein is a polypeptide comprising a utrophin N-tenninal portion and a dystrophin C-terminal portion. In one aspect of any of the embodiments, described herein is a polypeptide comprising a dystrophin N-terminal portion and a utrophin C-tenninal portion. In one aspect of any of the embodiments, described herein is a polypeptide, e.g., a microutrophin polypeptide, comprising a utrophin NT domain, a utrophin SLR domain 1. a utrophin SLR domain 2, a utrophin SLR domain 3, wherein the polypeptide is encoded bya codon optimized nucleic acid sequence. In some embodiments of any of the aspects, the polypeptide further comprises utrophin hinge domain 1, utrophin hinge domain 2, and utrophin hinge domain 4. In some embodiments of any of the aspects, the polypeptide further comprises utrophin SLR domain 22 and utrophin CR domain.

[0016] In some embodiments of any of the aspects, the codon optimized nucleic acid sequence is at least 85% identical to the sequence selected from the group consisting of SEQ ID NOs: 100-111.

[0017] In one aspect of any of the embodiments, described herein is a nucleic acid encoding a polypeptide described herein.

[0018] In some embodiments of any of the aspects, the nucleic acid comprises the sequence of one of SEQ ID NOs: 85-87, or a sequence having at least 85%. at least 90%, at least 95% or greater sequence identity to any of the foregoing sequences. In some embodiments of any of the aspects, one or more of the regions or domains is encoded by a codon-optimized sequence of one of SEQ ID NOs: 100-111, or a sequence having at least 80%. at least 85%, at least 90%. at least 95%, or greater sequence identity to any of the foregoing sequences. In some embodiments of any of the aspects, the utrophin NT region, the utrophin SLR domain 1, the utrophin SLR domain 2, and / or the utrophin SLR domain 3 are encoded by a codon-optimized sequence of one of SEQ ID NOs: 400-474, or a sequence having at least 80%, at least 85%. at least 90%, at least 95%, or greater sequence identity to any of the foregoing sequences. In some embodiments of any of the aspects, the utrophin NT region, the utrophin SLR domain 1, the utrophin SLR domain 2. and / or the utrophin SLR domain 3 are encoded by a codon-optimized sequence of one of SEQ ID NOs: 400-432 and 434-474, or a sequence having at least 80%. at least 85%, at least 90%, at least 95%, or greater sequence identity to any of the foregoing sequences. In some embodiments of any of the aspects, the utrophin NT region and the utrophin hinge 2 domain are encoded by a codon-optimized sequence of one of SEQ ID NOs: 400- 412 and 463-474, or a sequence having at least 80%, at least 85%, at least 90%, at least 95%, or greater sequence identity to any of the foregoing sequences.

[0019] In some embodiments of any of the aspects, the nucleic acid and / or sequence encoding a polypeptide is operably connected to a promoter. In some embodiments of any of the aspects, the promoter is a muscle-specific promoter. In some embodiments of any of the aspects, the musclespecific promoter is selected from the group consisting of: SP0524; SPc5-12; SP0525; SP0526; SP0527; SP0528; SCP1; and CRE0053. In some embodiments of any of the aspects, the musclespecific promoter is a SP0524 promoter or a SPc5-12 promoter. In some embodiments of any of the aspects, the muscle -specific promoter is a SP0524 promoter or a SP0527 promoter. In some embodiments of any of the aspects, the muscle-specific promoter is a SP0524 promoter. In some embodiments of any of the aspects, the muscle-specific promoter comprises the sequence of one of SEQ ID NOs: 18, 19, 20. 24, 25, 26, 27, 28. 29, or 83. In some embodiments of any of the aspects.the musclc-spccific promoter comprises the sequence of one of SEQ ID NOs: 18, 20, 24, 25, 26, 27, 28, or 29.

[0020] In some embodiments of any of the aspects, the nucleic acid and / or sequence encoding a polypeptide is flanked by AAV inverted terminal repeats (ITRs). In some embodiments of any of the aspects, the nucleic acid further comprises one or more additional regulatory elements and / or a polyA sequence.

[0021] In some embodiments of any of the aspects, the muscle-specific promoter is a SP0524 promoter and the polyA sequence is the sequence of SEQ ID NO: 52.

[0022] In some embodiments of any of the aspects, the one or more additional regulatory elements is selected from die group consisting of an enhancer, a 5’ untranslated region (5’UTR), an intron, a reverse RNA pol II terminator sequence, and combinations thereof. In some embodiments of any of the aspects, the intron is an I VS intron. In some embodiments of any of the aspects, the I VS intron comprises a nucleic acid sequence of SEQ ID NO: 22, a nucleic acid having at least 90%. 91%, 92%, 93%, 94%, 95%, 96%, 97%, or 98%, or 99% sequence identity thereto.

[0023] In one aspect of any of the embodiments, described herein is a vector comprising a nucleic acid sequence described herein. In one aspect of any of the embodiments, described herein is a vector comprising, from 5’ to 3’: a) a first inverted terminal repeat (ITR); b) a promoter; c) the nucleic acid sequence as described herein (e.g., encoding a polypeptide as described herein), operably linked to the promoter; d) a poly-A sequence 3’ of the nucleic acid sequence as described herein (e.g., encoding a polypeptide as described herein); and e) a second ITR.

[0024] In some embodiments of any of the aspects, the vector is an AAV vector, an adenoviral vector, a retroviral vector, or a lentiviral vector. In some embodiments of any of the aspects, the vector is an AAV vector.

[0025] In one aspect of any of the embodiments, described herein is a recombinant adeno- associated virus (rAAV) vector comprising in its genome a nucleic acid sequence as described herein (e.g., encoding a polypeptide as described herein). In one aspect of any of the embodiments, described herein is a recombinant adeno-associated virus (rAAV) vector comprising in its genome: a) 5‘ and 3’ AAV inverted terminal repeats (ITR) sequences; and b) located between the 5’ and 3’ ITRs, a nucleic acid sequence as described herein (e.g., encoding a polypeptide as described herein).In some embodiments of any of the aspects, the AAV genome further comprises at least one of: a) a 5’ ITR;b) an intron; c) a poly A sequence; and d) a 3’ ITR.In some embodiments of any of the aspects, the AAV genome comprises, in the 5’ to 3’ direction: a) a 5’ ITR; b) a muscle-specific promoter; c) an intron; d) a nucleic acid sequence as described herein (e.g.. encoding a polypeptide as described herein); e) a poly A sequence;1) a 3’ ITR.

[0026] In some embodiments of any of the aspects, the intron is selected from the group consisting of an IVS sequence, a MVM sequence, a HBB2 sequence, an CMVIE intron sequence, a UBC intron sequence, and a SV40 sequence. In some embodiments of any of the aspects, at least one of the 5’ ITR or 3’ITR comprises an insertion, deletion or substitution. In some embodiments of any of the aspects, one or more CpG islands in the ITR are removed.

[0027] In some embodiments of any of the aspects, the poly A sequence is a full length SV40 polyA sequence or HGF poly A sequence. In some embodiments of any of the aspects, poly A sequence is selected from SEQ ID NO: 23 or 52. or a nucleic acid sequence at least 80% sequence identity thereto.

[0028] In some embodiments of any of the aspects, the rAAV vector is a chimeric AAV vector, haploid AAV vector, a hybrid AAV vector or polyploid AAV vector. In some embodiments of any of the aspects, the rAAV vector is a rational haploid capsid, a mosaic AAV capsid, a chemically modified AAV capsid, or a AAV capsid from any AAV seroty pes. In some embodiments of any of the aspects, the rAAV capsid is a capsid from an AAV serotype selected from the group consisting of: AAV1, AAV2, AAV3, AAV4, AAV5, AAV6, AAV7, AAV8, AAV9, AAV10, AAV11, AAV12, AAV13, AAVrh74, AAVrhlO, pol, AAV9-PHP.B, AAV9-ePHP.B, AAV LK03, AAV Anc80L65, AAVDJ, AAVlA6ii, AAVlP5ii, AAV4Alii, AAV7P4i, AAV9AH, AAV9A2i, AAV9A6i, AAV9Pli, AAV9P2i, AAV9P5i, AAVrhlOAli, AAVrhlOA2i. AAVrhlOPli, AAV12P2ii, AAVSIOPli, AAV JEA, AAV2 3xA P2i, AAVDJ P2i, AAV 2i8, AAV2G9, AAV2.5i82g9, AAV2.5, AAVrl0pLDB_L2, AAVrl0pLDB_P31, AAV4E. AAVMyo, and AAV4A. In some embodiments of any of the aspects, the rAAV capsid is a capsid from an AAV serotype selected from the group consisting of: AAV9, AAV8. AAVrh74, and AAVMyo.

[0029] In one aspect of any of the embodiments, described herein is a pharmacal composition comprising the vector or rAAV vector as described herein, in a pharmaceutically acceptable carrier.2. In one aspect of any of the embodiments, described herein is a method of treating Duchenne Muscular Dystrophy (DMD) in a subject in need thereof, the method comprising administering a nucleic acid as described herein, or a vector as described herien, or a composition as described herein to the subject. In one aspect of any of the embodiments, described herein is a nucleic acid as described herein, or a vector as described herien, or a composition as described herein, for use in a method of treating DMD.

[0030] In some embodiments of any of the aspects, the administering is systemic administration. In some embodiments of any of the aspects, the systemic administration is intravenous administration. In some embodiments of any of the aspects, the administering is local administration. In some embodiments of any of the aspects, the local administration is by injection into a muscle. In some embodiments of any of the aspects, the rAAV vector is administered at a dosage range of between 1.0E9 vg / kg to 5.0E14vg / kg.BRIEF DESCRIPTION OF THE DRAWINGS

[0031] Fig. 1 A depicts a schematic of utrophin and dystrophin, reference sequences, and exemplary chimeric sequences described herein. Fig. IB depicts a key for Fig. 1A.

[0032] Fig. 2 depicts a schematic of the plasmid design for chimeric constructs described herein. In exemplary embodiments, the sequences are human, are not codon-optimized, and the cassette design does not comprise added restriction sites.

[0033] Fig. 3 depicts a table of construct identities.

[0034] Figs. 4A-4C depict normalized fatigue and twitch / tetanus responses after prior art DNA2 administration.

[0035] Figs. 5A-5C depict normalized fatigue and twitch / tetanus responses after SI- trophin_07_AE (DNA3) administration.

[0036] Figs. 6A-6C depict normalized fatigue and twitch / tetanus responses after SI-trophin_09 (DNA4) administration.

[0037] Figs. 7A-7C depict normalized fatigue and twitch / tetanus responses after SI- trophin_09_AE (DNA5) administration.

[0038] Figs. 8A-8C depict normalized fatigue and twitch / tetanus responses after prior art DNA6 administration.

[0039] Fig. 9 depicts a schematic of u Utrophin construct domains. The jiUtrophin schematic depicts the domains included in all of the codon-optimized sequences of Example 2.

[0040] Fig. 10 depicts a table of the constructs utilized in Example 2.

[0041] Fig 11 depicts a diagram of the experimental design for Example 2.

[0042] Figs. 12A-12C depicts the expression in the diaphragm.

[0043] Figs. 13A-13C depicts the expression in the heart.

[0044] Figs. 14A-14C depicts the expression in the heart.

[0045] Figs. 15A-15C depicts the expression in the heart.

[0046] Fig. 16 depicts graphs of Twitch and Tetanic force.

[0047] Fig. 17 depicts a graph of the different fatigue blocks used in Example 1.

[0048] Fig. 18 depicts an exemplary waveform for day 20 fatigue. Multiple tetanic stimulation, with 0.5 second rest period were used. The parameters are designed to fatigue the DMD control to at least 70% of initial force.

[0049] Figs. 19A-19B depict graphs of day 20 normalized fatigue (Fig. 19A) and normalized force at contraction #50 (Fig. 19B) for prior art DNA2.

[0050] Figs. 20A-20B depict graphs of day 20 normalized fatigue (Fig. 20 A) and normalized force at contraction #50 (Fig. 20B) for SI-trophin_07_AE (DNA3).

[0051] Figs. 21A-21B depict graphs of day 20 normalized fatigue (Fig. 21A) and normalized force at contraction #50 (Fig. 21B) for SI-trophin_09 (DNA4).

[0052] Figs. 22A-22B depict graphs of day 20 normalized fatigue (Fig. 22A) and normalized force at contraction #50 (Fig. 22B) for SI-trophin_09_AE (DNA5).

[0053] Figs. 23A-23B depict graphs of day 20 normalized fatigue (Fig. 23A) and normalized force at contraction #50 (Fig. 23B) for prior art DNA6.DETAILED DESCRIPTION

[0054] Aspects of the invention described herein arise from the identification of novel chimeric polypeptides that provide therapeutic effects in subjects with Duchenne muscular dystrophy (DMD). Nucleic acids encoding these polypeptides can be used to produce vectors for gene therapy (e.g., AAV based gene therapy) to treat DMD. Recombinant vectors (e.g., AAV) vectors and expression cassettes can be used to deliver the novel chimeric polypeptides, e.g., in expressible nucleic acid form, to the subject.

[0055] Furthermore, recombinant AAV ( rAAV) vector and constructs described herein for delivering the novel chimeric polypeptides to a subject comprise improvements such as, e.g.. incorporation of an intron upstream of the nucleic acid expressing the polypeptide and the promoter, and use of specific terminator sequences 3’ of nucleic acid encoding the polypeptide, such as, e.g., specific poly A sequences and / or terminator sequences.

[0056] In particular, described herein are viral vectors, e.g., using rAAV vectors as a non-limiting example, that comprise a nucleotide sequence containing inverted tenninal repeats (ITRs), a promoter (e.g., muscle specific promoter), a heterologous gene, a poly -A tail and potentially other regulator elements (e.g.. an intron) for use to treat DMD, where the heterologous gene is a nucleic acid encoding a polypeptide described herein. In some embodients. the vector, e.g., rAAV. can be administered to a patient in a therapeutically effective dose that is delivered to the appropriate tissue and / or organ (e.g., msucle tissue) for expression of the heterologous gene and treatment of thedisease, c.g., DMD.Chimeric Polypeptides

[0057] One aspect of the invention relates to a polypeptide comprising: a) a utrophin NT domain; b) a utrophin hinge 1 domain; c) a utrophin spectrin-like repeat (SLR) 1 domain; d) a utrophin spectrin-like repeat (SLR) 2 domain; e) a utrophin hinge 2 domain; f) a dystrophin SLR 20 domain; g) a dystrophin SLR 21 domain; h) a dystrophin SLR 22 domain; i) a dystrophin SLR 24 domain; j) a dystrophin hinge 4 domain; and k) a dystrophin cysteine rich (CR) domain.

[0058] In some embodiments of any of the aspects, the polypeptide further comprises a utrophin spectrin-like repeat (SLR) 3 domain.

[0059] In one aspect of any of the embodiments, described herein is a polypeptide comprising: a utrophin NT domain; a utrophin hinge 1 domain; a utrophin spectrin-like repeat (SLR) 1 domain; a utrophin spectrin-like repeat (SLR) 2 domain; a utrophin hinge 2 domain; a dystrophin SLR 20 domain; a dystrophin SLR 21 domain; a dystrophin SLR 22 domain; a dystrophin SLR 24 domain; a dystrophin hinge 4 domain; a dystrophin cysteine rich (CR) domain; and a utrophin spectrin-like repeat (SLR) 3 domain.

[0060] In some embodiments of any of the aspects, the polypeptide further comprises a dystrophin SLR 23 domain. In some embodiments of any of the aspects, the polypeptide further comprises a utrophin spectrin-like repeat (SLR) 3 domain and a dystrophin SLR 23 domain.

[0061] In some embodiments of any of the aspects, the polypeptide further comprises a domain selected from the group consisting of: a utrophin SLR 4 domain, a utrophin SLR 5 domain, a utrophin SLR 6 domain, a utrophin SLR 7 domain, a utrophin SLR 8 domain, a utrophin SLR 9 domain, autrophin SLR 10 domain, a utrophin SLR 11 domain, a utrophin SLR 12 domain, a utrophin SLR 13 domain, a utrophin SLR 14 domain, a utrophin SLR 15 domain, a utrophin SLR 16 domain, a utrophin SLR 17 domain, and a utrophin hinge 3 domain. In some embodiments of any of the aspects, the polypeptide further comprises at least one further domain selected from the group consisting of: a utrophin SLR 4 domain, a utrophin SLR 5 domain, a utrophin SLR 6 domain, a utrophin SLR 7 domain, a utrophin SLR 8 domain, a utrophin SLR 9 domain, a utrophin SLR 10 domain, a utrophin SLR 11 domain, a utrophin SLR 12 domain, a utrophin SLR 13 domain, a utrophin SLR 14 domain, a utrophin SLR 1 domain, a utrophin SLR 16 domain, a utrophin SLR 17 domain, and a utrophin hinge 3 domain. In some embodiments of any of die aspects, the polypeptide further comprises at least two further domains selected from the group consisting of: a utrophin SLR 4 domain, a utrophin SLR 5 domain, a utrophin SLR 6 domain, a utrophin SLR 7 domain, a utrophin SLR 8 domain, a utrophin SLR 9 domain, a utrophin SLR 10 domain, a utrophin SLR 11 domain, a utrophin SLR 12 domain, a utrophin SLR 13 domain, a utrophin SLR 14 domain, a utrophin SLR 15 domain, a utrophin SLR 16 domain, a utrophin SLR 17 domain, and a utrophin hinge 3 domain. In some embodiments of any of the aspects, the polypeptide further comprises at least three further domains selected from the group consisting of: a utrophin SLR 4 domain, a utrophin SLR 5 domain, a utrophin SLR 6 domain, a utrophin SLR 7 domain, a utrophin SLR 8 domain, a utrophin SLR 9 domain, a utrophin SLR 10 domain, a utrophin SLR 11 domain, a utrophin SLR 12 domain, a utrophin SLR 13 domain, a utrophin SLR 14 domain, a utrophin SLR 15 domain, a utrophin SLR 16 domain, a utrophin SLR 17 domain, and a utrophin hinge 3 domain. In some embodiments of any of the aspects, the polypeptide further comprises at least four further domains selected from the group consisting of: a utrophin SLR 4 domain, a utrophin SLR 5 domain, a utrophin SLR 6 domain, a utrophin SLR 7 domain, a utrophin SLR 8 domain, a utrophin SLR 9 domain, a utrophin SLR 10 domain, a utrophin SLR 11 domain, a utrophin SLR 12 domain, a utrophin SLR 13 domain, a utrophin SLR 14 domain, a utrophin SLR 15 domain, a utrophin SLR 16 domain, a utrophin SLR 17 domain, and a utrophin hinge 3 domain. In some embodiments of any of tire aspects, the poly peptide further comprises at least five further domains selected from the group consisting of: a utrophin SLR 4 domain, a utrophin SLR 5 domain, a utrophin SLR 6 domain, a utrophin SLR 7 domain, a utrophin SLR 8 domain, a utrophin SLR 9 domain, a utrophin SLR 10 domain, a utrophin SLR 11 domain, a utrophin SLR 12 domain, a utrophin SLR 13 domain, a utrophin SLR 14 domain, a utrophin SLR 15 domain, a utrophin SLR 16 domain, a utrophin SLR 17 domain, and a utrophin hinge 3 domain. In some embodiments of any of the aspects, the polypeptide further comprises at least six further domains selected from the group consisting of: a utrophin SLR 4 domain, a utrophin SLR 5 domain, a utrophin SLR 6 domain, a utrophin SLR 7 domain, a utrophin SLR 8 domain, a utrophin SLR 9 domain, a utrophin SLR 10 domain, a utrophin SLR 11 domain, a utrophin SLR 12 domain, a utrophin SLR 13domain, a utrophin SLR 14 domain, a utrophin SLR 15 domain, a utrophin SLR 16 domain, a utrophin SLR 17 domain, and a utrophin hinge 3 domain.

[0062] In some embodiments of any of the aspects, the polypeptide further comprises a domain selected from the group consisting of: a dystrophin SLR 4 domain, a dystrophin SLR 5 domain, a dystrophin SLR 6 domain, a dystrophin SLR 7 domain, a dystrophin SLR 8 domain, a dystrophin SLR 9 domain, a dystrophin SLR 10 domain, a dystrophin SLR 11 domain, a dystrophin SLR 12 domain, a dystrophin SLR 13 domain, a dystrophin SLR 14 domain, a dystrophin SLR 15 domain, a dystrophin SLR 16 domain, a dystrophin SLR 17 domain, dystrophin SLR 18 domain, and a dystrophin SLR 19 domain. In some embodiments of any of the aspects, the polypeptide further comprises at least one further domain selected from the group consisting of: a dystrophin SLR 4 domain, a dystrophin SLR 5 domain, a dystrophin SLR 6 domain, a dystrophin SLR 7 domain, a dystrophin SLR 8 domain, a dystrophin SLR 9 domain, a dystrophin SLR 10 domain, a dystrophin SLR 11 domain, a dystrophin SLR 12 domain, a dystrophin SLR 13 domain, a dystrophin SLR 14 domain, a dystrophin SLR 15 domain, a dystrophin SLR 16 domain, a dystrophin SLR 17 domain, dystrophin SLR 18 domain, and a dystrophin SLR 19 domain. In some embodiments of any of the aspects, the polypeptide further comprises at least two further domains selected from the group consisting of: a dystrophin SLR 4 domain, a dystrophin SLR 5 domain, a dystrophin SLR 6 domain, a dystrophin SLR 7 domain, a dystrophin SLR 8 domain, a dystrophin SLR 9 domain, a dystrophin SLR 10 domain, a dystrophin SLR 11 domain, a dystrophin SLR 12 domain, a dystrophin SLR 13 domain, a dystrophin SLR 14 domain, a dystrophin SLR 15 domain, a dystrophin SLR 16 domain, a dystrophin SLR 17 domain, dystrophin SLR 18 domain, and a dystrophin SLR 19 domain. In some embodiments of any of the aspects, the polypeptide further comprises at least three further domains selected from the group consisting of: a dystrophin SLR 4 domain, a dystrophin SLR 5 domain, a dystrophin SLR 6 domain, a dy strophin SLR 7 domain, a dystrophin SLR 8 domain, a dystrophin SLR 9 domain, a dystrophin SLR 10 domain, a dy strophin SLR 11 domain, a dystrophin SLR 12 domain, a dystrophin SLR 13 domain, a dystrophin SLR 14 domain, a dy strophin SLR 15 domain, a dystrophin SLR 16 domain, a dystrophin SLR 17 domain, dystrophin SLR 18 domain, and a dystrophin SLR 19 domain. In some embodiments of any of the aspects, the polypeptide further comprises at least four further domains selected from the group consisting of: a dystrophin SLR 4 domain, a dystrophin SLR 5 domain, a dystrophin SLR 6 domain, a dystrophin SLR 7 domain, a dystrophin SLR 8 domain, a dystrophin SLR 9 domain, a dystrophin SLR 10 domain, a dystrophin SLR 11 domain, a dystrophin SLR 12 domain, a dystrophin SLR 13 domain, a dystrophin SLR 14 domain, a dystrophin SLR 15 domain, a dystrophin SLR 16 domain, a dystrophin SLR 17 domain, dystrophin SLR 18 domain, and a dystrophin SLR 19 domain. In some embodiments of any of the aspects, the polypeptide further comprises at least five further domains selected from the group consisting of: a dystrophin SLR 4 domain, a dystrophin SLR 5 domain, a dystrophin SLR 6 domain, adystrophin SLR 7 domain, a dystrophin SLR 8 domain, a dystrophin SLR 9 domain, a dystrophin SLR 10 domain, a dystrophin SLR 11 domain, a dystrophin SLR 12 domain, a dystrophin SLR 13 domain, a dystrophin SLR 14 domain, a dystrophin SLR 15 domain, a dystrophin SLR 16 domain, a dystrophin SLR 17 domain, dystrophin SLR 18 domain, and a dystrophin SLR 19 domain. In some embodiments of any of the aspects, the polypeptide further comprises at least six further domains selected from the group consisting of: a dystrophin SLR 4 domain, a dystrophin SLR 5 domain, a dystrophin SLR 6 domain, a dystrophin SLR 7 domain, a dystrophin SLR 8 domain, a dystrophin SLR 9 domain, a dystrophin SLR 10 domain, a dystrophin SLR 11 domain, a dystrophin SLR 12 domain, a dystrophin SLR 13 domain, a dystrophin SLR 14 domain, a dystrophin SLR 15 domain, a dystrophin SLR 16 domain, a dystrophin SLR 17 domain, dystrophin SLR 18 domain, and a dystrophin SLR 19 domain.

[0063] In some embodiments of any of the aspects, the polypeptide comprises, from N-terminus to C-terminus: a) a utrophin NT domain; b) a utrophin hinge 1 domain; c) a utrophin spectrin-like repeat (SLR) 1 domain; d) a utrophin spectrin-like repeat (SLR) 2 domain; e) a utrophin hinge 2 domain; f) a dystrophin SLR 20 domain; g) a dystrophin SLR 21 domain; h) a dystrophin SLR 22 domain; i) a dystrophin SLR 24 domain; j) a dystrophin hinge 4 domain; and k) a dystrophin cysteine rich (CR) domain.In some embodiments of any of the aspects, the polypeptide comprises, from N-terminus to C- tenninus: a) a utrophin NT domain; b) a utrophin hinge 1 domain; c) a utrophin spectrin-like repeat (SLR) 1 domain; d) a utrophin spectrin-like repeat (SLR) 2 domain; e) a utrophin spectrin-like repeat (SLR) 3 domain; l a utrophin hinge 2 domain; g) a dystrophin SLR 20 domain; h) a dystrophin SLR 21 domain; i) a dystrophin SLR 22 domain; j) a dystrophin SLR 24 domain;k) a dystrophin hinge 4 domain; and l) a dystrophin cysteine rich (CR) domain.In some embodiments of any of tire aspects, the polypeptide comprises, from N-terminus to C- terminus: a) a utrophin NT domain; b) a utrophin hinge 1 domain; c) a utrophin spectrin-like repeat (SLR) 1 domain; d) a utrophin spectrin-like repeat (SLR) 2 domain; e) a utrophin hinge 2 domain; f) a dystrophin SLR 20 domain; g) a dystrophin SLR 21 domain; h) a dystrophin SLR 22 domain; i) a dystrophin SLR 23 domain; j) a dystrophin SLR 24 domain; k) a dystrophin hinge 4 domain; and l) a dystrophin cysteine rich (CR) domain.

[0064] In some embodiments of any of the aspects, the polypeptide further comprises a dystroglycan binding domain.

[0065] In some embodiments of any of the aspects, the polypeptide comprises, from N-terminus to C-terminus: a) a utrophin NT domain; b) a utrophin hinge 1 domain; c) a utrophin spectrin-like repeat (SLR) 1 domain; d) a utrophin spectrin-like repeat (SLR) 2 domain; e) a utrophin hinge 2 domain; f) a dy strophin SLR 20 domain; g) a dystrophin SLR 21 domain; h) a dystrophin SLR 22 domain; i) a dystrophin SLR 24 domain; j) a dystrophin hinge 4 domain; k) a dystrophin cysteine rich (CR) domain; and l) a dystroglycan binding domain.In some embodiments of any of the aspects, the polypeptide comprises, from N-terminus to C- terminus: a) a utrophin NT domain; b) a utrophin hinge 1 domain;c) a utrophin spcctrin-likc repeat (SLR) 1 domain; d) a utrophin spectrin-like repeat (SLR) 2 domain; e) a utrophin spectrin-like repeat (SLR) 3 domain; f a utrophin hinge 2 domain; g) a dystrophin SLR 20 domain; h) a dystrophin SLR 21 domain; i) a dystrophin SLR 22 domain; j) a dystrophin SLR 24 domain; k) a dystrophin hinge 4 domain; l) a dystrophin cysteine rich (CR) domain; and m) a dystroglycan binding domain.In some embodiments of any of Hie aspects, the polypeptide comprises, from N-terminus to C- terminus: a) a utrophin NT domain; b) a utrophin hinge 1 domain; c) a utrophin spectrin-like repeat (SLR) 1 domain; d) a utrophin spectrin-like repeat (SLR) 2 domain; e) a utrophin hinge 2 domain; f) a dystrophin SLR 20 domain; g) a dystrophin SLR 21 domain; h) a dystrophin SLR 22 domain; i) a dystrophin SLR 23 domain; j) a dystrophin SLR 24 domain; k) a dystrophin hinge 4 domain; l) a dy strophin cysteine rich (CR) domain; and m) a dy stroglycan binding domain.

[0066] In some embodiments of any of the aspects, the polypeptide consists of, from N-terminus to C-terminus: a) a utrophin NT domain; b) a utrophin hinge 1 domain; c) a utrophin spectrin-like repeat (SLR) 1 domain; d) a utrophin spectrin-like repeat (SLR) 2 domain; e) a utrophin hinge 2 domain; f) a dystrophin SLR 20 domain; g) a dystrophin SLR 21 domain; h) a dystrophin SLR 22 domain;i) a dystrophin SLR 24 domain; j) a dystrophin hinge 4 domain; k) a dystrophin cysteine rich (CR) domain; and l) a dystroglycan binding domain.In some embodiments of any of tire aspects, the polypeptide consists of, from N-terminus to C- terminus: a) a utrophin NT domain; b) a utrophin hinge 1 domain; c) a utrophin spectrin-like repeat (SLR) 1 domain; d) a utrophin spectrin-like repeat (SLR) 2 domain; e) a utrophin spectrin-like repeat (SLR) 3 domain; f) a utrophin hinge 2 domain; g) a dystrophin SLR 20 domain; h) a dystrophin SLR 21 domain; i) a dystrophin SLR 22 domain; j) a dystrophin SLR 24 domain; k) a dystrophin hinge 4 domain; l) a dystrophin cysteine rich (CR) domain; and m) a dystroglycan binding domain.In some embodiments of any of the aspects, the polypeptide consists of. from N-terminus to C- terminus: a) a utrophin NT domain; b) a utrophin hinge 1 domain; c) a utrophin spectrin-like repeat (SLR) 1 domain; d) a utrophin spectrin-like repeat (SLR) 2 domain; e) a utrophin hinge 2 domain; f) a dystrophin SLR 20 domain; g) a dystrophin SLR 21 domain; h) a dystrophin SLR 22 domain; i) a dystrophin SLR 23 domain; j) a dystrophin SLR 24 domain; k) a dystrophin hinge 4 domain; l) a dystrophin cysteine rich (CR) domain; and m) a dystroglycan binding domain.

[0067] The structures and sequences of utrophin and dystrophin are known in the art, including the structures and sequences of the domains of utrophin and dystrophin described herein. Forexample, the structures of utrophin and dystrophin arc described in Blake ct al. Brain Pathology 6:37- 47 (1996) and Muthu et al. PLoS One 7(7):e40066 (2012); each of which is incorporated by reference herein in its entirety .

[0068] In some embodiments of any of the aspects, a utrophin NT domain comprises a sequence which has at least 80% sequence identity to the sequence of SEQ ID NO: 51. In some embodiments of any of the aspects, a utrophin NT domain consists of a sequence which has at least 80% sequence identity to the sequence of SEQ ID NO: 51. In some embodiments of any of the aspects, a utrophin NT domain comprises a sequence which has at least 85% sequence identity to the sequence of SEQ ID NO: 51. In some embodiments of any of the aspects, a utrophin NT domain consists of a sequence which has at least 85% sequence identity to the sequence of SEQ ID NO: 51. In some embodiments of any of the aspects, a utrophin NT domain comprises a sequence which has at least 90% sequence identity to the sequence of SEQ ID NO: 51. In some embodiments of any of the aspects, a utrophin NT domain consists of a sequence which has at least 90% sequence identity to the sequence of SEQ ID NO: 51. In some embodiments of any of the aspects, a utrophin NT domain comprises a sequence which has at least 95% sequence identity to the sequence of SEQ ID NO: 51. In some embodiments of any of the aspects, a utrophin NT domain consists of a sequence which has at least 95% sequence identity to the sequence of SEQ ID NO: 51. In some embodiments of any of the aspects, a utrophin NT domain comprises a sequence which has at least 98% sequence identity to the sequence of SEQ ID NO: 51. In some embodiments of any of the aspects, a utrophin NT domain consists of a sequence which has at least 98% sequence identity to the sequence of SEQ ID NO: 51. In some embodiments of any of the aspects, a utrophin NT domain comprises a sequence which has at least 99% sequence identity to the sequence of SEQ ID NO: 51. In some embodiments of any of the aspects, a utrophin NT domain consists of a sequence which has at least 99% sequence identity to the sequence of SEQ ID NO: 51. In some embodiments of any of the aspects, a utrophin NT domain comprises the sequence of SEQ ID NO: 51. In some embodiments of any of the aspects, a utrophin NT domain consists of the sequence of SEQ ID NO: 51.

[0069] SEQ ID NO: 51 MAKYGEHEASPDNGQNEFSDIIKSRSDEHNDVQKKTFTKWINARFSKSGKPPINDMFTDLKD GRKLLDLLEGLTGTSLPKERGSTRVHALNNVNRVLQVLHQNNVELVNIGGTDIVDGNHKLT LGLLWSIILHWQVKDVMKDVMSDLQQTNSEKILLSWVRQTTRPYSQVNVLNFTTSWTDGLA FNAVLHRHKPDLFSWDKVVKMSPIERLEHAFSKAQTYLGIEKLLDPEDVAVQLPDKKSIIMY

[0070] In some embodiments of any of the aspects, a utrophin NT domain comprises a sequence which has at least 80% sequence identity to the sequence of SEQ ID NO: 4. In some embodiments of any of the aspects, a utrophin NT domain consists of a sequence which has at least 80% sequence identity to the sequence of SEQ ID NO: 4. In some embodiments of any of the aspects, a utrophin NT domain comprises a sequence which has at least 85% sequence identity to the sequence of SEQ IDNO: 4. In some embodiments of any of the aspects, a utrophin NT domain consists of a sequence which has at least 85% sequence identity to the sequence of SEQ ID NO: 4. In some embodiments of any of the aspects, a utrophin NT domain comprises a sequence which has at least 90% sequence identity to the sequence of SEQ ID NO: 4. In some embodiments of any of the aspects, a utrophin NT domain consists of a sequence which has at least 90% sequence identity to tire sequence of SEQ ID NO: 4. In some embodiments of any of the aspects, a utrophin NT domain comprises a sequence which has at least 95% sequence identity to the sequence of SEQ ID NO: 4. In some embodiments of any of the aspects, a utrophin NT domain consists of a sequence which has at least 95% sequence identity to the sequence of SEQ ID NO: 4. In some embodiments of any of the aspects, a utrophin NT domain comprises a sequence which has at least 98% sequence identity to the sequence of SEQ ID NO: 4. In some embodiments of any of the aspects, a utrophin NT domain consists of a sequence which has at least 98% sequence identity to the sequence of SEQ ID NO: 4. In some embodiments of any of the aspects, a utrophin NT domain comprises a sequence which has at least 99% sequence identity to the sequence of SEQ ID NO: 4. In some embodiments of any of the aspects, a utrophin NT domain consists of a sequence which has at least 99% sequence identity to the sequence of SEQ ID NO: 4. In some embodiments of any of the aspects, a utrophin NT domain comprises the sequence of SEQ ID NO: 4. In some embodiments of any of the aspects, a utrophin NT domain consists of the sequence of SEQ ID NO: 4.

[0071] Utrophin NT domain (SEQ ID NO : 4)MAKYGEHEASPDNGQNEFSDIIKSRSDEHNDVQKKTFTKWINARFSKSGKPPINDMFTDLKD GRKLLDLLEGLTGTSLPKERGSTRVHALNNVNRVLQVLHQNNVELVNIGGTDIVDGNHKLT LGLLWSIILHWQVKDVMKDVMSDLQQTNSEKILLSWVRQTTRPYSQVNVLNFTTSWTDGLA FNAVLHRHKPDLFSWDKVVKMSPIERLEHAFSKAQTYLGIEKLLDPEDVAVQLPDKKSIIMY LTSLFEVLPQQVTID AIREVE

[0072] In some embodiments of any of the aspects, a utrophin hinge 1 domain comprises a sequence which has at least 80% sequence identity to the sequence of SEQ ID NO: 5. In some embodiments of any of the aspects, a utrophin hinge 1 domain consists of a sequence which has at least 80% sequence identity to the sequence of SEQ ID NO: 5. In some embodiments of any of the aspects, a utrophin hinge 1 domain comprises a sequence which has at least 85% sequence identity to the sequence of SEQ ID NO: 5. In some embodiments of any of the aspects, a utrophin hinge 1 domain consists of a sequence which has at least 85% sequence identity to the sequence of SEQ ID NO: 5. In some embodiments of any of the aspects, a utrophin hinge 1 domain comprises a sequence which has at least 90% sequence identity to the sequence of SEQ ID NO: 5. In some embodiments of any of the aspects, a utrophin hinge 1 domain consists of a sequence which has at least 90% sequence identity to the sequence of SEQ ID NO: 5. In some embodiments of any of the aspects, a utrophin hinge 1 domain comprises a sequence which has at least 95% sequence identity to the sequence ofSEQ ID NO: 5. In some embodiments of any of the aspects, a utrophin hinge 1 domain consists of a sequence which has at least 95% sequence identity to the sequence of SEQ ID NO: 5. In some embodiments of any of the aspects, a utrophin hinge 1 domain comprises a sequence which has at least 98% sequence identity to the sequence of SEQ ID NO: 5. In some embodiments of any of the aspects, a utrophin hinge 1 domain consists of a sequence which has at least 98% sequence identity to the sequence of SEQ ID NO: 5. In some embodiments of any of the aspects, a utrophin hinge 1 domain comprises a sequence which has at least 99% sequence identity to the sequence of SEQ ID NO: 5. In some embodiments of any of the aspects, a utrophin hinge 1 domain consists of a sequence which has at least 99% sequence identity to the sequence of SEQ ID NO: 5. In some embodiments of any of the aspects, a utrophin hinge 1 domain comprises the sequence of SEQ ID NO: 5. In some embodiments of any of the aspects, a utrophin hinge 1 domain consists of the sequence of SEQ ID NO: 5.

[0073] Utrophin hinge 1 domain (SEQ ID NO: 5) TLPRKYKKECEEEAINIQSTAPEEEHESPRAETPST

[0074] In some embodiments of any of the aspects, a utrophin SLR 1 domain comprises a sequence which has at least 80% sequence identity' to the sequence of SEQ ID NO: 6. In some embodiments of any of the aspects, a utrophin SLR 1 domain consists of a sequence which has at least 80% sequence identity to the sequence of SEQ ID NO: 6. In some embodiments of any of the aspects, a utrophin SLR 1 domain comprises a sequence which has at least 85% sequence identity to the sequence of SEQ ID NO: 6. In some embodiments of any of the aspects, a utrophin SLR 1 domain consists of a sequence which has at least 85% sequence identity to the sequence of SEQ ID NO: 6. In some embodiments of any of the aspects, a utrophin SLR 1 domain comprises a sequence which has at least 90% sequence identity to the sequence of SEQ ID NO: 6. In some embodiments of any of the aspects, a utrophin SLR 1 domain consists of a sequence which has at least 90% sequence identity' to the sequence of SEQ ID NO: 6. In some embodiments of any of the aspects, a utrophin SLR 1 domain comprises a sequence which has at least 95% sequence identity to the sequence of SEQ ID NO: 6. In some embodiments of any of the aspects, a utrophin SLR 1 domain consists of a sequence which has at least 95% sequence identity to the sequence of SEQ ID NO: 6. In some embodiments of any of the aspects, a utrophin SLR 1 domain comprises a sequence which has at least 98% sequence identity to the sequence of SEQ ID NO: 6. In some embodiments of any of the aspects, a utrophin SLR 1 domain consists of a sequence which has at least 98% sequence identity to the sequence of SEQ ID NO: 6. In some embodiments of any of the aspects, a utrophin SLR 1 domain comprises a sequence which has at least 99% sequence identity to the sequence of SEQ ID NO: 6. In some embodiments of any of the aspects, a utrophin SLR 1 domain consists of a sequence which has at least 99% sequence identity to the sequence of SEQ ID NO: 6. In some embodiments of any of the aspects,a utropliin SLR 1 domain comprises the sequence of SEQ ID NO: 6. In some embodiments of any of the aspects, a utrophin SLR 1 domain consists of the sequence of SEQ ID NO: 6.

[0075] Utrophin SLR 1 domain (SEQ ID NO: 6)DSYQIALEEVLTWLLSAEDTFQEQDDISDDVEEVKDQFATHEAFMMELTAHQSSVGS VLQAGNQLITQGTLSDEEEFEIQEQMTLLNARWEALRVESMDRQSRLH

[0076] In some embodiments of any of the aspects, a utrophin SLR 2 domain comprises a sequence which has at least 80% sequence identity to the sequence of SEQ ID NO: 7. In some embodiments of any of the aspects, a utrophin SLR 2 domain consists of a sequence which has at least 80% sequence identity7to the sequence of SEQ ID NO: 7. In some embodiments of any of the aspects, a utrophin SLR 2 domain comprises a sequence which has at least 85% sequence identity to the sequence of SEQ ID NO: 7. In some embodiments of any of the aspects, a utrophin SLR 2 domain consists of a sequence which has at least 85% sequence identity to the sequence of SEQ ID NO: 7. In some embodiments of any of the aspects, a utrophin SLR 2 domain comprises a sequence which has at least 90% sequence identity to the sequence of SEQ ID NO: 7. In some embodiments of any of the aspects, a utrophin SLR 2 domain consists of a sequence which has at least 90% sequence identity7to the sequence of SEQ ID NO: 7. In some embodiments of any of the aspects, a utrophin SLR 2 domain comprises a sequence which has at least 95% sequence identity to the sequence of SEQ ID NO: 7. In some embodiments of any of the aspects, a utrophin SLR 2 domain consists of a sequence which has at least 95% sequence identity to the sequence of SEQ ID NO: 7. In some embodiments of any of the aspects, a utrophin SLR 2 domain comprises a sequence which has at least 98% sequence identity to the sequence of SEQ ID NO: 7. In some embodiments of any of the aspects, a utrophin SLR 2 domain consists of a sequence which has at least 98% sequence identity to the sequence of SEQ ID NO: 7. In some embodiments of any of the aspects, a utrophin SLR 2 domain comprises a sequence which has at least 99% sequence identity to the sequence of SEQ ID NO: 7. In some embodiments of any of the aspects, a utrophin SLR 2 domain consists of a sequence which has at least 99% sequence identity to the sequence of SEQ ID NO: 7. In some embodiments of any of the aspects, a utrophin SLR 2 domain comprises the sequence of SEQ ID NO: 7. In some embodiments of any of the aspects, a utrophin SLR 2 domain consists of the sequence of SEQ ID NO: 7.

[0077] Utrophin SLR 2 domain (SEQ ID NO: 7)ELQKKQLQQLSAWLTLTEERIQKMETCPLDDDVKSLQKLLEEHKSLQSDLEAEQVK VNSLTHMVVIVDENSGESATAILEDQLQKLGERWTAVCRWTEERWNRLQ

[0078] In some embodiments of any of the aspects, a utrophin hinge 2 domain comprises a sequence which has at least 80% sequence identity' to the sequence of SEQ ID NO: 8. In some embodiments of any of the aspects, a utrophin hinge 2 domain consists of a sequence which has at least 80% sequence identity to the sequence of SEQ ID NO: 8. In some embodiments of any of theaspects, a utropliin hinge 2 domain comprises a sequence which has at least 85% sequence identity to the sequence of SEQ ID NO: 8. In some embodiments of any of the aspects, a utrophin hinge 2 domain consists of a sequence which has at least 85% sequence identity to the sequence of SEQ ID NO: 8. In some embodiments of any of the aspects, a utrophin hinge 2 domain comprises a sequence which has at least 90% sequence identity to the sequence of SEQ ID NO: 8. In some embodiments of any of the aspects, a utrophin hinge 2 domain consists of a sequence which has at least 90% sequence identity to the sequence of SEQ ID NO: 8. In some embodiments of any of the aspects, a utrophin hinge 2 domain comprises a sequence which has at least 95% sequence identity to the sequence of SEQ ID NO: 8. In some embodiments of any of the aspects, a utrophin hinge 2 domain consists of a sequence which has at least 95% sequence identity to the sequence of SEQ ID NO: 8. In some embodiments of any of the aspects, a utrophin hinge 2 domain comprises a sequence which has at least 98% sequence identity to the sequence of SEQ ID NO: 8. In some embodiments of any of the aspects, a utrophin hinge 2 domain consists of a sequence which has at least 98% sequence identity to the sequence of SEQ ID NO: 8. In some embodiments of any of the aspects, a utrophin hinge 2 domain comprises a sequence which has at least 99% sequence identity to the sequence of SEQ ID NO: 8. In some embodiments of any of the aspects, a utrophin hinge 2 domain consists of a sequence which has at least 99% sequence identity to the sequence of SEQ ID NO: 8. In some embodiments of any of the aspects, a utrophin hinge 2 domain comprises the sequence of SEQ ID NO: 8. In some embodiments of any of the aspects, a utrophin hinge 2 domain consists of the sequence of SEQ ID NO: 8.

[0079] Utrophin hinge 2 domain (SEQ ID NO: 8)AVAKLGMSQIPQKDLLETVRVREQAITKKSKQELPPPPPPKKRQIHV

[0080] In some embodiments of any of the aspects, a dystrophin SLR 20 domain comprises a sequence which has at least 80% sequence identity to the sequence of SEQ ID NO: 9. In some embodiments of any of the aspects, a dystrophin SLR 20 domain consists of a sequence which has at least 80% sequence identity' to the sequence of SEQ ID NO: 9. In some embodiments of any of the aspects, a dystrophin SLR 20 domain comprises a sequence which has at least 85% sequence identity to the sequence of SEQ ID NO: 9. In some embodiments of any of the aspects, a dystrophin SLR 20 domain consists of a sequence which has at least 85% sequence identity to the sequence of SEQ ID NO: 9. In some embodiments of any of the aspects, a dystrophin SLR 20 domain comprises a sequence which has at least 90% sequence identity to the sequence of SEQ ID NO: 9. In some embodiments of any of the aspects, a dystrophin SLR 20 domain consists of a sequence which has at least 90% sequence identity to the sequence of SEQ ID NO: 9. In some embodiments of any of the aspects, a dystrophin SLR 20 domain comprises a sequence which has at least 95% sequence identity to the sequence of SEQ ID NO: 9. In some embodiments of any of the aspects, a dystrophin SLR 20 domain consists of a sequence which has at least 95% sequence identity to the sequence of SEQ IDNO: 9. In some embodiments of any of the aspects, a dystrophin SLR 20 domain comprises a sequence which has at least 98% sequence identity to the sequence of SEQ ID NO: 9. In some embodiments of any of the aspects, a dystrophin SLR 20 domain consists of a sequence which has at least 98% sequence identity to the sequence of SEQ ID NO: 9. In some embodiments of any of the aspects, a dystrophin SLR 20 domain comprises a sequence which has at least 99% sequence identity to the sequence of SEQ ID NO: 9. In some embodiments of any of the aspects, a dystrophin SLR 20 domain consists of a sequence which has at least 99% sequence identity to the sequence of SEQ ID NO: 9. In some embodiments of any of the aspects, a dystrophin SLR 20 domain comprises the sequence of SEQ ID NO: 9. In some embodiments of any of the aspects, a dystrophin SLR 20 domain consists of the sequence of SEQ ID NO: 9.

[0081] Dystrophin SLR 20 domain (SEQ ID NO: 9)ALADFNRAWTELTDWLSLLDQVIKSQRVMVGDLEDINEMIIKQKATMQDLEQRRPQ LEELITAAQNLKNKTSNQEARTIITDRIERIQNQWDEVQEHLQNRRQQLNE

[0082] In some embodiments of any of the aspects, a dystrophin SLR 20 domain comprises a sequence which has at least 80% sequence identity’ to the sequence of SEQ ID NO: 500. In some embodiments of any of the aspects, a dystrophin SLR 20 domain consists of a sequence which has at least 80% sequence identity to the sequence of SEQ ID NO: 500. In some embodiments of any of the aspects, a dystrophin SLR 20 domain comprises a sequence which has at least 85% sequence identity’ to the sequence of SEQ ID NO: 500. In some embodiments of any of the aspects, a dystrophin SLR 20 domain consists of a sequence which has at least 85% sequence identity to the sequence of SEQ ID NO: 500. In some embodiments of any of the aspects, a dystrophin SLR 20 domain comprises a sequence which has at least 90% sequence identity' to the sequence of SEQ ID NO: 500. In some embodiments of any of the aspects, a dystrophin SLR 20 domain consists of a sequence which has at least 90% sequence identity to the sequence of SEQ ID NO: 500. In some embodiments of any of the aspects, a dystrophin SLR 20 domain comprises a sequence which has at least 95% sequence identity to the sequence of SEQ ID NO: 500. In some embodiments of any of the aspects, a dystrophin SLR 20 domain consists of a sequence which has at least 95% sequence identity’ to the sequence of SEQ ID NO: 500. In some embodiments of any of the aspects, a dystrophin SLR 20 domain comprises a sequence which has at least 98% sequence identity to the sequence of SEQ ID NO: 500. In some embodiments of any of the aspects, a dystrophin SLR 20 domain consists of a sequence which has at least 98% sequence identity to the sequence of SEQ ID NO: 500. In some embodiments of any of the aspects, a dystrophin SLR 20 domain comprises a sequence which has at least 99% sequence identity to the sequence of SEQ ID NO: 500. In some embodiments of any of the aspects, a dystrophin SLR 20 domain consists of a sequence which has at least 99% sequence identity to the sequence of SEQ ID NO: 500. In some embodiments of any of the aspects, a dystrophin SLR 20 domain comprises thesequence of SEQ ID NO: 500. In some embodiments of any of the aspects, a dystrophin SLR 20 domain consists of the sequence of SEQ ID NO: 500.

[0083] Dystrophin SLR 20 domain (SEQ ID NO: 500)FNRAWTELTDWLSLLDQVIKSQRVMVGDLEDINEMIIKQKATMQDLEQRRPQLEELITAAQNLKNKTSNQEARTIITDRIERIQNQWDEVQEHLQNRRQQLNE

[0084] In some embodiments of any of the aspects, a dystrophin SLR 21 domain comprises a sequence which has at least 80% sequence identity to tire sequence of SEQ ID NO: 10. In some embodiments of any of the aspects, a dystrophin SLR 21 domain consists of a sequence which has at least 80% sequence identity to the sequence of SEQ ID NO: 10. In some embodiments of any of the aspects, a dystrophin SLR 21 domain comprises a sequence which has at least 85% sequence identity to the sequence of SEQ ID NO: 10. In some embodiments of any of the aspects, a dystrophin SLR 21 domain consists of a sequence which has at least 85% sequence identity to the sequence of SEQ ID NO: 10. In some embodiments of any of the aspects, a dystrophin SLR 21 domain comprises a sequence which has at least 90% sequence identity to the sequence of SEQ ID NO: 10. In some embodiments of any of the aspects, a dystrophin SLR 21 domain consists of a sequence which has at least 90% sequence identity to the sequence of SEQ ID NO: 10. In some embodiments of any of the aspects, a dystrophin SLR 21 domain comprises a sequence which has at least 95% sequence identity to the sequence of SEQ ID NO: 10. In some embodiments of any of the aspects, a dystrophin SLR 21 domain consists of a sequence which has at least 95% sequence identity to the sequence of SEQ ID NO: 10. In some embodiments of any of the aspects, a dystrophin SLR 21 domain comprises a sequence which has at least 98% sequence identity to the sequence of SEQ ID NO: 10. In some embodiments of any of the aspects, a dystrophin SLR 21 domain consists of a sequence which has at least 98% sequence identity to the sequence of SEQ ID NO: 10. In some embodiments of any of the aspects, a dystrophin SLR 21 domain comprises a sequence which has at least 99% sequence identity to the sequence of SEQ ID NO: 10. In some embodiments of any of the aspects, a dystrophin SLR 21 domain consists of a sequence which has at least 99% sequence identity to the sequence of SEQ ID NO: 10. In some embodiments of any of the aspects, a dystrophin SLR 21 domain comprises the sequence of SEQ ID NO: 10. In some embodiments of any of the aspects, a dystrophin SLR 21 domain consists of the sequence of SEQ ID NO: 10.

[0085] Dystrophin SLR 21 domain (SEQ ID NO: 10)MLKDSTQWLEAKEEAEQVLGQARAKLESWKEGPYTVDAIQKKJTETKQLAKDLRQ WQTNVDVANDLALKLLRDYSADDTRKVHMITENINASWRSIHKRVSEREAALEE

[0086] In some embodiments of any of the aspects, a dystrophin SLR 21 domain comprises a sequence which has at least 80% sequence identity to tire sequence of SEQ ID NO: 501. In some embodiments of any of the aspects, a dystrophin SLR 21 domain consists of a sequence which has atleast 80% sequence identity to the sequence of SEQ ID NO: 501. In some embodiments of any of the aspects, a dystrophin SLR 21 domain comprises a sequence which has at least 85% sequence identity to the sequence of SEQ ID NO: 501. In some embodiments of any of the aspects, a dystrophin SLR 21 domain consists of a sequence which has at least 85% sequence identity to the sequence of SEQ ID NO: 501. In some embodiments of any of the aspects, a dystrophin SLR 21 domain comprises a sequence which has at least 90% sequence identity to the sequence of SEQ ID NO: 501. In some embodiments of any of the aspects, a dystrophin SLR 21 domain consists of a sequence which has at least 90% sequence identity to the sequence of SEQ ID NO: 501. In some embodiments of any of the aspects, a dystrophin SLR 21 domain comprises a sequence which has at least 95% sequence identity to the sequence of SEQ ID NO: 501. In some embodiments of any of the aspects, a dystrophin SLR 21 domain consists of a sequence which has at least 95% sequence identity to the sequence of SEQ ID NO: 501. In some embodiments of any of the aspects, a dystrophin SLR 21 domain comprises a sequence which has at least 98% sequence identity’ to the sequence of SEQ ID NO: 501. In some embodiments of any of the aspects, a dystrophin SLR 21 domain consists of a sequence which has at least 98% sequence identity to the sequence of SEQ ID NO: 501. In some embodiments of any of the aspects, a dystrophin SLR 21 domain comprises a sequence which has at least 99% sequence identity to the sequence of SEQ ID NO: 501. In some embodiments of any of the aspects, a dystrophin SLR 21 domain consists of a sequence which has at least 99% sequence identity to the sequence of SEQ ID NO: 501. In some embodiments of any of the aspects, a dystrophin SLR 21 domain comprises the sequence of SEQ ID NO: 501. In some embodiments of any of the aspects, a dystrophin SLR 21 domain consists of the sequence of SEQ ID NO: 501.

[0087] Dystrophin SLR 21 domain (SEQ ID NO: 501)KDSTQWLEAKEEAEQVLGQARAKLESWKEGPYTVDAIQKKITETKQLAKDLRQWQ TNVDVANDLALKLLRDYSADDTRKVHMITENINASWRSIH

[0088] In some embodiments of any of the aspects, a dystrophin SLR 22 domain comprises a sequence which has at least 80% sequence identity to the sequence of SEQ ID NO: 11. In some embodiments of any of the aspects, a dystrophin SLR 22 domain consists of a sequence which has at least 80% sequence identity to the sequence of SEQ ID NO: 11. In some embodiments of any of the aspects, a dystrophin SLR 22 domain comprises a sequence which has at least 85% sequence identity to the sequence of SEQ ID NO: 11. In some embodiments of any of the aspects, a dystrophin SLR 22 domain consists of a sequence which has at least 85% sequence identity' to the sequence of SEQ ID NO: 11. In some embodiments of any of the aspects, a dystrophin SLR 22 domain comprises a sequence which has at least 90% sequence identity' to the sequence of SEQ ID NO: 11 . In some embodiments of any of the aspects, a dystrophin SLR 22 domain consists of a sequence which has at least 90% sequence identity to the sequence of SEQ ID NO: 11. In some embodiments of any of the aspects, a dystrophin SLR 22 domain comprises a sequence which has at least 95% sequence identity'to the sequence of SEQ ID NO: 11. In some embodiments of any of the aspects, a dystrophin SLR 22 domain consists of a sequence which has at least 95% sequence identity to the sequence of SEQ ID NO: 11. In some embodiments of any of the aspects, a dystrophin SLR 22 domain comprises a sequence which has at least 98% sequence identity to tire sequence of SEQ ID NO: 11. In some embodiments of any of the aspects, a dystrophin SLR 22 domain consists of a sequence which has at least 98% sequence identity to the sequence of SEQ ID NO: 11. In some embodiments of any of the aspects, a dystrophin SLR 22 domain comprises a sequence which has at least 99% sequence identity to the sequence of SEQ ID NO: 11. In some embodiments of any of the aspects, a dystrophin SLR 22 domain consists of a sequence which has at least 99% sequence identity to the sequence of SEQ ID NO: 11. In some embodiments of any of the aspects, a dystrophin SLR 22 domain comprises the sequence of SEQ ID NO: 11. In some embodiments of any of the aspects, a dystrophin SLR 22 domain consists of the sequence of SEQ ID NO: 11.

[0089] Dystrophin SLR 22 domain (SEQ ID NO: 11)THRLLQQFPLDLEKFLAWLTEAETTANVLQDATRKERLLEDSKGVKELMKQWQDL QGEIEAHTDVYHNLDENSQKILRSLEGSDDAVLLQRRLDNMNFKWSELRKKSLNIRS HLEA

[0090] In some embodiments of any of the aspects, a dystrophin SLR 22 domain comprises a sequence which has at least 80% sequence identity to the sequence of SEQ ID NO: 502. In some embodiments of any of the aspects, a dystrophin SLR 22 domain consists of a sequence which has at least 80% sequence identity to the sequence of SEQ ID NO: 502. In some embodiments of any of the aspects, a dystrophin SLR 22 domain comprises a sequence which has at least 85% sequence identity to the sequence of SEQ ID NO: 502. In some embodiments of any of the aspects, a dystrophin SLR 22 domain consists of a sequence which has at least 85% sequence identity to the sequence of SEQ ID NO: 502. In some embodiments of any of the aspects, a dystrophin SLR 22 domain comprises a sequence which has at least 90% sequence identity to the sequence of SEQ ID NO: 502. In some embodiments of any of the aspects, a dystrophin SLR 22 domain consists of a sequence which has at least 90% sequence identity to the sequence of SEQ ID NO: 502. In some embodiments of any of the aspects, a dystrophin SLR 22 domain comprises a sequence which has at least 95% sequence identity to the sequence of SEQ ID NO: 502. In some embodiments of any of the aspects, a dystrophin SLR 22 domain consists of a sequence which has at least 95% sequence identity to the sequence of SEQ ID NO: 502. In some embodiments of any? of the aspects, a dystrophin SLR 22 domain comprises a sequence which has at least 98% sequence identity to the sequence of SEQ ID NO: 502. In some embodiments of any of the aspects, a dystrophin SLR 22 domain consists of a sequence which has at least 98% sequence identity to the sequence of SEQ ID NO: 502. In some embodiments of any of the aspects, a dystrophin SLR 22 domain comprises a sequence which has at least 99% sequence identity to the sequence of SEQ ID NO: 502. In some embodiments of any of the aspects, a dystrophin SLR22 domain consists of a sequence which has at least 99% sequence identity to the sequence of SEQ ID NO: 502. In some embodiments of any of the aspects, a dystrophin SLR 22 domain comprises the sequence of SEQ ID NO: 502. In some embodiments of any of the aspects, a dystrophin SLR 22 domain consists of the sequence of SEQ ID NO: 502.

[0091] Dystrophin SLR 22 domain (SEQ ID NO: 502)RLLQQFPLDLEKFLAWLTEAETTANVLQDATRKERLLEDSKGVKELMKQWQDLQG EIEAHTDVYHNLDENSQKILRSLEGSDDAVLLQRRLDNMNFKWSELRKKSLNIRSHL EA

[0092] In some embodiments of any of the aspects, a dystrophin SLR 23 domain comprises a sequence which has at least 80% sequence identity to the sequence of SEQ ID NO: 12. In some embodiments of any of the aspects, a dystrophin SLR 23 domain consists of a sequence which has at least 80% sequence identity to the sequence of SEQ ID NO: 12. In some embodiments of any of the aspects, a dystrophin SLR 23 domain comprises a sequence which has at least 85% sequence identity to the sequence of SEQ ID NO: 12. In some embodiments of any of the aspects, a dystrophin SLR 23 domain consists of a sequence which has at least 85% sequence identity to the sequence of SEQ ID NO: 12. hi some embodiments of any of the aspects, a dystrophin SLR 23 domain comprises a sequence which has at least 90% sequence identity to the sequence of SEQ ID NO: 12. In some embodiments of any of the aspects, a dystrophin SLR 23 domain consists of a sequence which has at least 90% sequence identity to the sequence of SEQ ID NO: 12. In some embodiments of any of the aspects, a dystrophin SLR 23 domain comprises a sequence which has at least 95% sequence identity to the sequence of SEQ ID NO: 12. In some embodiments of any of the aspects, a dystrophin SLR 23 domain consists of a sequence which has at least 95% sequence identity to the sequence of SEQ ID NO: 12. In some embodiments of any of the aspects, a dystrophin SLR 23 domain comprises a sequence which has at least 98% sequence identity’ to the sequence of SEQ ID NO: 12. In some embodiments of any of the aspects, a dystrophin SLR 23 domain consists of a sequence which has at least 98% sequence identity to the sequence of SEQ ID NO: 12. In some embodiments of any of the aspects, a dystrophin SLR 23 domain comprises a sequence which has at least 99% sequence identity to the sequence of SEQ ID NO: 12. In some embodiments of any of the aspects, a dystrophin SLR 23 domain consists of a sequence which has at least 99% sequence identity' to the sequence of SEQ ID NO: 12. In some embodiments of any of the aspects, a dystrophin SLR 23 domain comprises the sequence of SEQ ID NO: 12. In some embodiments of any of the aspects, a dystrophin SLR 23 domain consists of the sequence of SEQ ID NO: 12.

[0093] Dystrophin SLR 23 domain (SEQ ID NO: 12)KRLHLSLQELLVWLQLKDDELSRQAPIGGDFPAVQKQNDVHRAFKRELKTKEPVIM STLETVRIFLTEQPLEGLEKLYQEPRELPPEERAQNVTRLLRKQAEEVNTEWEKLNLH SADWQRKID

[0094] In some embodiments of any of the aspects, a dystrophin SLR 24 domain comprises a sequence which has at least 80% sequence identity to the sequence of SEQ ID NO: 13. In some embodiments of any of the aspects, a dystrophin SLR 24 domain consists of a sequence which has at least 80% sequence identity to die sequence of SEQ ID NO: 13. In some embodiments of any of the aspects, a dystrophin SLR 24 domain comprises a sequence which has at least 85% sequence identity to the sequence of SEQ ID NO: 13. In some embodiments of any of the aspects, a dystrophin SLR 24 domain consists of a sequence which has at least 85% sequence identity to the sequence of SEQ ID NO: 13. In some embodiments of any of the aspects, a dystrophin SLR 24 domain comprises a sequence which has at least 90% sequence identity to the sequence of SEQ ID NO: 13. In some embodiments of any of the aspects, a dystrophin SLR 24 domain consists of a sequence which has at least 90% sequence identity to the sequence of SEQ ID NO: 13. In some embodiments of any of the aspects, a dystrophin SLR 24 domain comprises a sequence which has at least 95% sequence identity to the sequence of SEQ ID NO: 13. In some embodiments of any of the aspects, a dystrophin SLR 24 domain consists of a sequence which has at least 95% sequence identity’ to the sequence of SEQ ID NO: 13. In some embodiments of any of the aspects, a dystrophin SLR 24 domain comprises a sequence which has at least 98% sequence identity' to the sequence of SEQ ID NO: 13. In some embodiments of any of the aspects, a dystrophin SLR 24 domain consists of a sequence which has at least 98% sequence identity to the sequence of SEQ ID NO: 13. In some embodiments of any of the aspects, a dystrophin SLR 24 domain comprises a sequence which has at least 99% sequence identity’ to the sequence of SEQ ID NO: 13. In some embodiments of any of the aspects, a dystrophin SLR 24 domain consists of a sequence which has at least 99% sequence identity' to the sequence of SEQ ID NO: 13. In some embodiments of any of the aspects, a dystrophin SLR 24 domain comprises the sequence of SEQ ID NO: 13. In some embodiments of any of the aspects, a dystrophin SLR 24 domain consists of the sequence of SEQ ID NO: 13.

[0095] Dystrophin SLR 24 domain (SEQ ID NO: 13) rlqelqeatd eldlklrqae vikgswqpvg dllidslqdh lekvkalrge iaplkenvsh vndlarqlt Igiqlspynl stledlntrw kllqvavedr vrqlhe

[0096] In some embodiments of any of the aspects, a dystrophin SLR 24 domain comprises a sequence which has at least 80% sequence identity to the sequence of SEQ ID NO: 503. In some embodiments of any of the aspects, a dystrophin SLR 24 domain consists of a sequence which has at least 80% sequence identity to the sequence of SEQ ID NO: 503. In some embodiments of any of the aspects, a dystrophin SLR 24 domain comprises a sequence which has at least 85% sequence identity to the sequence of SEQ ID NO: 503. In some embodiments of any of the aspects, a dystrophin SLR 24 domain consists of a sequence which has at least 85% sequence identity to the sequence of SEQ ID NO: 503. In some embodiments of any of the aspects, a dystrophin SLR 24 domain comprises a sequence which has at least 90% sequence identity' to the sequence of SEQ ID NO: 503. In someembodiments of any of the aspects, a dystrophin SLR 24 domain consists of a sequence which has at least 90% sequence identity to the sequence of SEQ ID NO: 503. In some embodiments of any of the aspects, a dystrophin SLR 24 domain comprises a sequence which has at least 95% sequence identity to the sequence of SEQ ID NO: 503. In some embodiments of any of the aspects, a dystrophin SLR 24 domain consists of a sequence which has at least 95% sequence identity to the sequence of SEQ ID NO: 503. In some embodiments of any of the aspects, a dystrophin SLR 24 domain comprises a sequence which has at least 98% sequence identity to the sequence of SEQ ID NO: 503. In some embodiments of any of the aspects, a dystrophin SLR 24 domain consists of a sequence which has at least 98% sequence identity to the sequence of SEQ ID NO: 503. In some embodiments of any of the aspects, a dystrophin SLR 24 domain comprises a sequence which has at least 99% sequence identity to the sequence of SEQ ID NO: 503. In some embodiments of any of the aspects, a dystrophin SLR 24 domain consists of a sequence which has at least 99% sequence identity to the sequence of SEQ ID NO: 503. In some embodiments of any of the aspects, a dystrophin SLR 24 domain comprises the sequence of SEQ ID NO: 503. In some embodiments of any of the aspects, a dystrophin SLR 24 domain consists of the sequence of SEQ ID NO: 503.

[0097] Dystrophin SLR 24 domain (SEQ ID NO: 503)RLQELQEATDELDLKLRQAEVIKGSWQPVGDLLIDSLQDHLEKVKALRGEIAPLKENVSHVN DLARQLTTLGIQLSPYNLSTLEDLNTRWKLLQVAVEDRVRQLHE

[0098] In some embodiments of any of the aspects, a dystrophin hinge 4 domain comprises a sequence which has at least 80% sequence identity' to the sequence of SEQ ID NO: 14. In some embodiments of any of the aspects, a dystrophin hinge 4 domain consists of a sequence which has at least 80% sequence identity to the sequence of SEQ ID NO: 14. In some embodiments of any of the aspects, a dystrophin hinge 4 domain comprises a sequence which has at least 85% sequence identity to the sequence of SEQ ID NO: 14. In some embodiments of any of the aspects, a dystrophin hinge 4 domain consists of a sequence which has at least 85% sequence identity to the sequence of SEQ ID NO: 14. In some embodiments of any of the aspects, a dystrophin hinge 4 domain comprises a sequence which has at least 90% sequence identity to the sequence of SEQ ID NO: 14. In some embodiments of any of the aspects, a dystrophin hinge 4 domain consists of a sequence which has at least 90% sequence identity to the sequence of SEQ ID NO: 14. In some embodiments of any of the aspects, a dystrophin hinge 4 domain comprises a sequence which has at least 95% sequence identity to the sequence of SEQ ID NO: 14. In some embodiments of any of the aspects, a dystrophin hinge 4 domain consists of a sequence which has at least 95% sequence identity to the sequence of SEQ ID NO: 14. In some embodiments of any of the aspects, a dystrophin hinge 4 domain comprises a sequence which has at least 98% sequence identity to the sequence of SEQ ID NO: 14. In some embodiments of any of the aspects, a dystrophin hinge 4 domain consists of a sequence which has at least 98% sequence identity to the sequence of SEQ ID NO: 14. In some embodiments of any of theaspects, a dystrophin hinge 4 domain comprises a sequence which has at least 99% sequence identity to the sequence of SEQ ID NO: 14. In some embodiments of any of the aspects, a dystrophin hinge 4 domain consists of a sequence which has at least 99% sequence identity to the sequence of SEQ ID NO: 14. In some embodiments of any of the aspects, a dystrophin hinge 4 domain comprises the sequence of SEQ ID NO: 14. In some embodiments of any of the aspects, a dystrophin hinge 4 domain consists of the sequence of SEQ ID NO: 14.

[0099] Dystrophin hinge 4 domain (SEQ ID NO: 14)LSTLEDLNTRWKLLQVAVEDRVRQLHEAHRDFGPASQHFLSTSVQGPWERAISPNK VPYYINHETQTTCWDHPKMTELYQSLADLNNVRFSAYRTAMKL

[0100] In some embodiments of any of the aspects, a dystrophin hinge 4 domain comprises a sequence which has at least 80% sequence identity to the sequence of SEQ ID NO: 504. In some embodiments of any of the aspects, a dystrophin hinge 4 domain consists of a sequence which has at least 80% sequence identity to the sequence of SEQ ID NO: 504. In some embodiments of any of the aspects, a dystrophin hinge 4 domain comprises a sequence which has at least 85% sequence identity to the sequence of SEQ ID NO: 504. In some embodiments of any of the aspects, a dystrophin hinge 4 domain consists of a sequence which has at least 85% sequence identity to the sequence of SEQ ID NO: 504. In some embodiments of any? of the aspects, a dystrophin hinge 4 domain comprises a sequence which has at least 90% sequence identity to the sequence of SEQ ID NO: 504. In some embodiments of any of the aspects, a dystrophin hinge 4 domain consists of a sequence which has at least 90% sequence identity to the sequence of SEQ ID NO: 504. In some embodiments of any of the aspects, a dystrophin hinge 4 domain comprises a sequence which has at least 95% sequence identity to the sequence of SEQ ID NO: 504. In some embodiments of any of the aspects, a dystrophin hinge 4 domain consists of a sequence which has at least 95% sequence identity to the sequence of SEQ ID NO: 504. In some embodiments of any of the aspects, a dystrophin hinge 4 domain comprises a sequence which has at least 98% sequence identity to the sequence of SEQ ID NO: 504. In some embodiments of any of the aspects, a dy strophin hinge 4 domain consists of a sequence which has at least 98% sequence identity to the sequence of SEQ ID NO: 504. In some embodiments of any of the aspects, a dystrophin hinge 4 domain comprises a sequence which has at least 99% sequence identity to the sequence of SEQ ID NO: 504. In some embodiments of any of the aspects, a dystrophin hinge 4 domain consists of a sequence which has at least 99% sequence identity to the sequence of SEQ ID NO: 504. In some embodiments of any of the aspects, a dystrophin hinge 4 domain comprises the sequence of SEQ ID NO: 504. In some embodiments of any of the aspects, a dystrophin hinge 4 domain consists of the sequence of SEQ ID NO: 504.

[0101] Dystrophin hinge 4 domain (SEQ ID NO: 504)AHRDFGPASQHFLSTSVQGPWERAISPNKVPYYINHETQTTCWDHPKMTELYQSLA DLNNVRFSAYRTAMKL

[0102] In some embodiments of any of the aspects, a dystrophin CR domain comprises a sequence which has at least 80% sequence identity to the sequence of SEQ ID NO: 505. In some embodiments of any of the aspects, a dystrophin CR domain consists of a sequence which has at least 80% sequence identity to the sequence of SEQ ID NO: 505. In some embodiments of any of the aspects, a dystrophin CR domain comprises a sequence which has at least 85% sequence identity to the sequence of SEQ ID NO: 505. In some embodiments of any of the aspects, a dystrophin CR domain consists of a sequence which has at least 85% sequence identity to the sequence of SEQ ID NO: 505. In some embodiments of any of the aspects, a dystrophin CR domain comprises a sequence which has at least 90% sequence identity to the sequence of SEQ ID NO: 505. In some embodiments of any of the aspects, a dystrophin CR domain consists of a sequence which has at least 90% sequence identity to the sequence of SEQ ID NO: 505. In some embodiments of any of the aspects, a dystrophin CR domain comprises a sequence which has at least 95% sequence identity to the sequence of SEQ ID NO: 505. In some embodiments of any of the aspects, a dystrophin CR domain consists of a sequence which has at least 95% sequence identity to the sequence of SEQ ID NO: 505. In some embodiments of any of the aspects, a dystrophin CR domain comprises a sequence which has at least 98% sequence identity to the sequence of SEQ ID NO: 505. In some embodiments of any of the aspects, a dystrophin CR domain consists of a sequence which has at least 98% sequence identity to the sequence of SEQ ID NO: 505. In some embodiments of any of the aspects, a dystrophin CR domain comprises a sequence which has at least 99% sequence identity to the sequence of SEQ ID NO: 505. In some embodiments of any of the aspects, a dystrophin CR domain consists of a sequence which has at least 99% sequence identity to the sequence of SEQ ID NO: 505. In some embodiments of any of the aspects, a dystrophin CR domain comprises the sequence of SEQ ID NO: 505. In some embodiments of any of the aspects, a dy strophin CR domain consists of the sequence of SEQ ID NO: 505.|00103] Dystrophin CR domain (SEQ ID NO: 505)TSVQGPWERAISPNKVPYYINHETQTTCWDHPKMQGPWERAISPNKVPYYINHETQT TCWDHPKMTELYQSLADLNNVRFSAYRTAMKLRRLQKALCLDLLSLSAACDALDQ HNLKQNDQPMDILQIINCLTTIYDRLEQEHNNLVNVPLCVDMCLNWLLNVYDTGRT GRIRVLSFKTGIISLCKAHLEDKYRYLFKQVASSTGFCDQRRLGLLLHDSIQIPRQLGE VASFGGSNIEPSVRSCFQFANNKPE1EAALFLDWMRLEPQSMVWLPVLHRVAAAETA KHQAKCNICKECPIIGFRYRSLKHFNYDICQSCFFSGRVAKGHKMHYPMVEYCTPTT SGEDVRDFAKVLKNKFRTKRYFAKHPRMGYLPVQTVLEGDNMETKHQAKCNICKE CPIIGFRYRSLKHFNYDICQSCFFSGRVAKGHKMHYPMVEYCTPTT

[0104] In some embodiments of any of the aspects, a dystrophin CR domain comprises a sequence which has at least 80% sequence identity to the sequence of SEQ ID NO: 15. In someembodiments of any of the aspects, a dystrophin CR domain consists of a sequence which has at least 80% sequence identity to the sequence of SEQ ID NO: 15. In some embodiments of any of the aspects, a dystrophin CR domain comprises a sequence which has at least 85% sequence identity to the sequence of SEQ ID NO: 15. In some embodiments of any of the aspects, a dystrophin CR domain consists of a sequence which has at least 85% sequence identity to tire sequence of SEQ ID NO: 15. In some embodiments of any of the aspects, a dystrophin CR domain comprises a sequence which has at least 90% sequence identity to the sequence of SEQ ID NO: 15. In some embodiments of any of the aspects, a dystrophin CR domain consists of a sequence which has at least 90% sequence identity to the sequence of SEQ ID NO: 15. In some embodiments of any of the aspects, a dystrophin CR domain comprises a sequence which has at least 95% sequence identity to the sequence of SEQ ID NO: 15. In some embodiments of any of the aspects, a dystrophin CR domain consists of a sequence which has at least 95% sequence identity to the sequence of SEQ ID NO: 15. In some embodiments of any of the aspects, a dystrophin CR domain comprises a sequence which has at least 98% sequence identity to the sequence of SEQ ID NO: 15. In some embodiments of any of the aspects, a dystrophin CR domain consists of a sequence which has at least 98% sequence identity to the sequence of SEQ ID NO: 15. In some embodiments of any of the aspects, a dystrophin CR domain comprises a sequence which has at least 99% sequence identity to the sequence of SEQ ID NO: 15. In some embodiments of any of the aspects, a dystrophin CR domain consists of a sequence which has at least 99% sequence identity to the sequence of SEQ ID NO: 15. In some embodiments of any of the aspects, a dystrophin CR domain comprises the sequence of SEQ ID NO: 15. In some embodiments of any of the aspects, a dystrophin CR domain consists of the sequence of SEQ ID NO: 15.

[0105] Dystrophin CR domain (SEQ ID NO: 15) nvrfs ayrtamklrr Iqkalcldll slsaacdald qhnlkqndqp mdilqiincl ttiydrleqe hnnlvnvplc vdmclnwlln vydtgrtgri rvlsfktgii slckahledk yrylfkqvas stgfcdqrrl glllhdsiqi prqlgevasf ggsniepsvr scfqfannkp eieaalfldw mrlepqsmvw Ipvlhr

[0106] In some embodiments of any of the aspects, a utrophin SLR 3 domain comprises a sequence which has at least 80% sequence identity to the sequence of SEQ ID NO: 16. In some embodiments of any of the aspects, a utrophin SLR 3 domain consists of a sequence which has at least 80% sequence identity to the sequence of SEQ ID NO: 16. In some embodiments of any of the aspects, a utrophin SLR 3 domain comprises a sequence which has at least 85% sequence identity to the sequence of SEQ ID NO: 16. In some embodiments of any of the aspects, a utrophin SLR 3 domain consists of a sequence which has at least 85% sequence identity to the sequence of SEQ ID NO: 16. In some embodiments of any of the aspects, a utrophin SLR 3 domain comprises a sequence which has at least 90% sequence identity to the sequence of SEQ ID NO: 16. In some embodimentsof any of the aspects, a utrophin SLR 3 domain consists of a sequence which has at least 90% sequence identity to the sequence of SEQ ID NO: 16. In some embodiments of any of the aspects, a utrophin SLR 3 domain comprises a sequence which has at least 95% sequence identity to the sequence of SEQ ID NO: 16. In some embodiments of any of the aspects, a utrophin SLR 3 domain consists of a sequence which has at least 95% sequence identity to tire sequence of SEQ ID NO: 16. In some embodiments of any of the aspects, a utrophin SLR 3 domain comprises a sequence which has at least 98% sequence identity to the sequence of SEQ ID NO: 16. In some embodiments of any of the aspects, a utrophin SLR 3 domain consists of a sequence which has at least 98% sequence identity to the sequence of SEQ ID NO: 16. In some embodiments of any of the aspects, a utrophin SLR 3 domain comprises a sequence which has at least 99% sequence identity to the sequence of SEQ ID NO: 16. In some embodiments of any of the aspects, a utrophin SLR 3 domain consists of a sequence which has at least 99% sequence identity’ to the sequence of SEQ ID NO: 16. In some embodiments of any of the aspects, a utrophin SLR 3 domain comprises the sequence of SEQ ID NO: 16. In some embodiments of any of the aspects, a utrophin SLR 3 domain consists of the sequence of SEQ ID NO: 16.

[0107] Utrophin SLR 3 domain (SEQ ID NO: 16)QELLEEQCLLKAWLTEKEEALNKVQTSNFKDQKELSVSVRRLAILKEDMEMKRQTL DQLSEIGQDVGQLLDNSKASKKINSDSEELTQRWDSLVQRLEDSSNQVT

[0108] In some embodiments of any of the aspects, a dystroglycan binding domain comprises a sequence which has at least 80% sequence identity to the sequence of SEQ ID NO: 17. In some embodiments of any of the aspects, a dystroglycan binding domain consists of a sequence which has at least 80% sequence identity to the sequence of SEQ ID NO: 17. In some embodiments of any of the aspects, a dystroglycan binding domain comprises a sequence which has at least 85% sequence identity to the sequence of SEQ ID NO: 17. In some embodiments of any of the aspects, a dystroglycan binding domain consists of a sequence which has at least 85% sequence identity to the sequence of SEQ ID NO: 17. In some embodiments of any of the aspects, a dystroglycan binding domain comprises a sequence which has at least 90% sequence identity to the sequence of SEQ ID NO: 17. In some embodiments of any of the aspects, a dystrogly can binding domain consists of a sequence which has at least 90% sequence identity to the sequence of SEQ ID NO: 17. In some embodiments of any of the aspects, a dy stroglycan binding domain comprises a sequence which has at least 95% sequence identity to the sequence of SEQ ID NO: 17. In some embodiments of any of the aspects, a dystroglycan binding domain consists of a sequence which has at least 95% sequence identity to the sequence of SEQ ID NO: 17. In some embodiments of any of the aspects, a dystroglycan binding domain comprises a sequence which has at least 98% sequence identity to the sequence of SEQ ID NO: 17. In some embodiments of any of the aspects, a dystroglycan binding domain consists of a sequence which has at least 98% sequence identity to the sequence of SEQ IDNO: 17. In some embodiments of any of the aspects, a dystroglycan binding domain comprises a sequence which has at least 99% sequence identity to the sequence of SEQ ID NO: 17. In some embodiments of any of the aspects, a dystroglycan binding domain consists of a sequence which has at least 99% sequence identity to the sequence of SEQ ID NO: 17. In some embodiments of any of the aspects, a dystroglycan binding domain comprises the sequence of SEQ ID NO: 17. In some embodiments of any of the aspects, a dystroglycan binding domain consists of the sequence of SEQ ID NO: 17.

[0109] Dystroglycan binding domain (SEQ ID NO: 17) rvaaa etakhqakcn ickecpiigf ryrslkhfhy dicqscffsg rvakghkmhy pmveyctptt sgedvrdfak vlknkfrtkr y fakhprmgy Ipvqtvlegd nmet

[0110] In some embodiments of any of the aspects, a dystroglycan binding domain comprises a sequence which has at least 80% sequence identity to the sequence of SEQ ID NO: 506. In some embodiments of any of the aspects, a dystroglycan binding domain consists of a sequence which has at least 80% sequence identity to the sequence of SEQ ID NO: 506. In some embodiments of any of the aspects, a dystroglycan binding domain comprises a sequence which has at least 85% sequence identity to the sequence of SEQ ID NO: 506. In some embodiments of any of the aspects, a dystroglycan binding domain consists of a sequence which has at least 85% sequence identity to the sequence of SEQ ID NO: 506. In some embodiments of any of the aspects, a dystroglycan binding domain comprises a sequence which has at least 90% sequence identity to the sequence of SEQ ID NO: 506. In some embodiments of any of the aspects, a dystroglycan binding domain consists of a sequence which has at least 90% sequence identity to the sequence of SEQ ID NO: 506. In some embodiments of any of the aspects, a dystroglycan binding domain comprises a sequence which has at least 95% sequence identity to the sequence of SEQ ID NO: 506. In some embodiments of any of the aspects, a dystroglycan binding domain consists of a sequence which has at least 95% sequence identity to the sequence of SEQ ID NO: 506. In some embodiments of any of the aspects, a dystroglycan binding domain comprises a sequence which has at least 98% sequence identity to the sequence of SEQ ID NO: 506. In some embodiments of any of the aspects, a dystroglycan binding domain consists of a sequence which has at least 98% sequence identity to the sequence of SEQ ID NO: 506. In some embodiments of any of the aspects, a dystroglycan binding domain comprises a sequence which has at least 99% sequence identity to the sequence of SEQ ID NO: 506. In some embodiments of any of the aspects, a dystroglycan binding domain consists of a sequence which has at least 99% sequence identity to the sequence of SEQ ID NO: 506. In some embodiments of any of the aspects, a dystroglycan binding domain comprises the sequence of SEQ ID NO: 506. In some embodiments of any of the aspects, a dystroglycan binding domain consists of the sequence of SEQ ID NO: 506.

[0111] Dystroglycan binding domain (SEQ ID NO: 506) TTCWDHPKMTELYQSLADLNNVRFSAYRTAMKLRRLQKALCLDLLSLSAACDALDQHNLK QNDQPMDILQIINCLTTIYDRLEQEHNNLVNVPLCVDMCLNWLLNVYDTGRTGRIRVLSFKT GIISLCKAHLEDKYRYLFKQVASSTGFCDQRRLGLLLHDSIQIPRQLGEVASFGGSNIEPSVRS CFQFANNKPEIEAALFLDWMRLEPQSMVWLPVLHRVAAAETAKHQAKCNICKECPIIGFRYR SLKHFNYDICQSCFFSGRVAKGHKMHYPMVEYCTPTTSGEDVRDFAKVLKNKFRTKRYFAK HPRMGYLPVQTVLEGDNMET

[0112] In some embodiments, the polypeptide has the polypeptide sequence set forth in one of SEQ ID NOs: 1-3. or a polypeptide having at least 90%, 91%, 92%, 93%. 94%, 95%, 96%, 97%. or 98%, or 99% sequence identity thereto.

[0113] In some embodiments of any of the aspects, the polypeptide comprises a sequence which has at least 80% sequence identity to the sequence of SEQ ID NO: 1. In some embodiments of any of the aspects, the polypeptide consists of a sequence which has at least 80% sequence identity to the sequence of SEQ ID NO: 1. In some embodiments of any of the aspects, the polypeptide comprises a sequence which has at least 85% sequence identity to the sequence of SEQ ID NO: 1. In some embodiments of any of the aspects, the polypeptide consists of a sequence which has at least 85% sequence identity to the sequence of SEQ ID NO: 1. In some embodiments of any of the aspects, the polypeptide comprises a sequence which has at least 90% sequence identity to the sequence of SEQ ID NO: 1. In some embodiments of any of the aspects, the polypeptide consists of a sequence which has at least 90% sequence identity to the sequence of SEQ ID NO: 1. In some embodiments of any of the aspects, the polypeptide comprises a sequence which has at least 95% sequence identity to the sequence of SEQ ID NO: 1. In some embodiments of any of the aspects, the polypeptide consists of a sequence which has at least 95% sequence identity to the sequence of SEQ ID NO: 1. In some embodiments of any of the aspects, the poly peptide comprises a sequence which has at least 98% sequence identity to the sequence of SEQ ID NO: 1. In some embodiments of any of the aspects, the polypeptide consists of a sequence which has at least 98% sequence identity to the sequence of SEQ ID NO: 1. In some embodiments of any of the aspects, the polypeptide comprises a sequence which has at least 99% sequence identity to the sequence of SEQ ID NO: 1. In some embodiments of any of the aspects, the polypeptide consists of a sequence which has at least 99% sequence identity to the sequence of SEQ ID NO: 1. In some embodiments of any of the aspects, the polypeptide comprises the sequence of SEQ ID NO: 1. In some embodiments of any of the aspects, the polypeptide consists of the sequence of SEQ ID NO: 1. In some embodiments, the polypeptide has the polypeptide sequence set forth in SEQ ID NO: 1, or a polypeptide having at least 90%, 91%, 92%. 93%, 94%, 95%, 96%, 97%, or 98%, or 99% sequence identity thereto.

[0114] In some embodiments of any of the aspects, the polypeptide comprises a sequence which has at least 80% sequence identity to the sequence of SEQ ID NO: 2. In some embodiments of any of the aspects, the polypeptide consists of a sequence which has at least 80% sequence identity to the sequence of SEQ ID NO: 2. In some embodiments of any of the aspects, the polypeptide comprises a sequence which has at least 85% sequence identity to tire sequence of SEQ ID NO: 2. In some embodiments of any of the aspects, the polypeptide consists of a sequence which has at least 85% sequence identity to the sequence of SEQ ID NO: 2. In some embodiments of any of the aspects, the polypeptide comprises a sequence which has at least 90% sequence identity to the sequence of SEQ ID NO: 2. In some embodiments of any of the aspects, the polypeptide consists of a sequence which has at least 90% sequence identity to the sequence of SEQ ID NO: 2. In some embodiments of any of the aspects, the polypeptide comprises a sequence which has at least 95% sequence identity to the sequence of SEQ ID NO: 2. In some embodiments of any of the aspects, the polypeptide consists of a sequence which has at least 95% sequence identity to the sequence of SEQ ID NO: 2. In some embodiments of any of the aspects, the polypeptide comprises a sequence which has at least 98% sequence identity to the sequence of SEQ ID NO: 2. In some embodiments of any of the aspects, the polypeptide consists of a sequence which has at least 98% sequence identity’ to the sequence of SEQ ID NO: 2. In some embodiments of any of the aspects, the polypeptide comprises a sequence which has at least 99% sequence identity to the sequence of SEQ ID NO: 2. In some embodiments of any of the aspects, the polypeptide consists of a sequence which has at least 99% sequence identity to the sequence of SEQ ID NO: 2. In some embodiments of any of the aspects, the polypeptide comprises the sequence of SEQ ID NO: 2. In some embodiments of any of the aspects, the polypeptide consists of the sequence of SEQ ID NO: 2. In some embodiments, the polypeptide has the polypeptide sequence set forth in SEQ ID NO: 2, or a polypeptide having at least 90%, 91%. 92%, 93%, 94%, 95%, 96%, 97%. or 98%, or 99% sequence identity thereto.

[0115] In some embodiments of any of the aspects, the poly peptide comprises a sequence which has at least 80% sequence identity to the sequence of SEQ ID NO: 3. In some embodiments of any of the aspects, the polypeptide consists of a sequence which has at least 80% sequence identity to the sequence of SEQ ID NO: 3. In some embodiments of any of the aspects, the polypeptide comprises a sequence which has at least 85% sequence identity to the sequence of SEQ ID NO: 3. In some embodiments of any of the aspects, the polypeptide consists of a sequence which has at least 85% sequence identity to the sequence of SEQ ID NO: 3. In some embodiments of any of the aspects, the polypeptide comprises a sequence which has at least 90% sequence identity to the sequence of SEQ ID NO: 3. In some embodiments of any of the aspects, the polypeptide consists of a sequence which has at least 90% sequence identity to the sequence of SEQ ID NO: 3. In some embodiments of any of the aspects, the polypeptide comprises a sequence which has at least 95% sequence identity to the sequence of SEQ ID NO: 3. In some embodiments of any of the aspects, the polypeptide consists of asequence which has at least 95% sequence identity to the sequence of SEQ ID NO: 3. In some embodiments of any of the aspects, the polypeptide comprises a sequence which has at least 98% sequence identity to die sequence of SEQ ID NO: 3. In some embodiments of any of the aspects, the polypeptide consists of a sequence which has at least 98% sequence identity to the sequence of SEQ ID NO: 3. In some embodiments of any of the aspects, the polypeptide comprises a sequence which has at least 99% sequence identity to the sequence of SEQ ID NO: 3. In some embodiments of any of the aspects, the polypeptide consists of a sequence which has at least 99% sequence identity to the sequence of SEQ ID NO: 3. In some embodiments of any of the aspects, the polypeptide comprises the sequence of SEQ ID NO: 3. In some embodiments of any of the aspects, the polypeptide consists of the sequence of SEQ ID NO: 3. In some embodiments, the polypeptide has the polypeptide sequence set forth in SEQ ID NO: 3, or a polypeptide having at least 90%, 91%, 92%. 93%, 94%, 95%, 96%, 97%, or 98%, or 99% sequence identity thereto.

[0116] SI-trophin_07_AE_protein (SEQ ID NO: 1)1 makygeheas pdngqnefsd iiksrsdehn dvqkktftkw inarfsksgk ppindmftdl 61 kdgrklldll egltgtslpk ergstrvhal nnvnrvlqvl hqnnvelvni ggtdivdgnh 121 kltlgllwsi ilhwqvkdvm kdvmsdlqqt nsekillswv rqtrpysqv nvlnfttswt 181 dglafnavlh rhkpdlfswd kvvkmspier lehafskaqt ylgieklldp edvavqlpdk 241 ksiimyltsl fevlpqqvti dairevetlp rkykkeceee ainiqstape eehespraet 301 pstvtevdmd Idsyqialee vltwllsaed tfqeqddisd dveevkdqfa theafmmelt 361 ahqssvgsvl qagnqlitqg tlsdeeefei qeqmtllnar wealrvesmd rqsrlhdvlm 421 elqkkqlqql sawltlteer iqkmetcpld ddvkslqkll eehkslqsdl eaeqvkvnsl 481 thmvvivden sgesataile dqlqklgerw taverwteer wnrlqeinia vaklgmsqip 541 qkdlletvrv reqaitkksk qelppppppk krqihvalad fnrawtcltd wlslldqvik 601 sqrvmvgdle dinemiikqk atmqdleqrr pqleelitaa qnlknktsnq eartiitdri 661 eriqnqwdev qehlqnrrqq Inemlkdstq wleakeeaeq vlgqarakle swkegpytvd 721 aiqkkitetk qlakdlrqwq tnvdvandla Ikllrdysad dtrkvhmite ninaswrsih 781 krvsereaal eethrllqqf pldlekflaw Iteaettanv Iqdatrkerl ledskgvkel 841 mkqwqdlqge ieahtdvyhn Idensqkilr slegsddavl Iqrrldnmnf kwselrkksl 901 nirshleass dqwkrlhlsl qellvwlqlk ddelsrqapi ggdfpavqkq ndvhrafkre 961 Iktkepvims tletvriflt eqpleglekl yqeprelppe eraqnvtrll rkqaeevnte 1021 weklnlhsad wqrkidetle rlqelqeatd eldlklrqae vikgswqpvg dllidslqdh 1081 lekvkalrge iaplkenvsh vndlarqlt Igiqlspynl stledlntrw kllqvavedr 1141 vrqlheahrd fgpasqhfls tsvqgpwera ispnkvpyyi nhetqttcwd hpkmtelyqs 1201 ladlnnvrfs ayrtamklrr Iqkalcldll slsaacdald qhnlkqndqp mdilqiincl 1261 ttiydrleqe hnnlvnvplc vdmclnwlln vydtgrtgri rvlsfktgii slckahledk 1321 yrylfkqvas stgfcdqrrl glllhdsiqi prqlgevasf ggsniepsvr scfqfannkp 1381 eieaalfldw mrlepqsmvw Ipvlhrvaaa etakhqakcn ickecpiigf ryrslkhfny 1441 dicqscffsg rvakghkmhy pmveyctpt sgedvrdfak vlknkfrtkr yfakhprmgy 1501 Ipvqtvlegd nmet

[0117] SI-trophin_09 protein (SEQ ID NO: 2)1 makygeheas pdngqnefsd iiksrsdehn dvqkktftkw inarfsksgk ppindmftdl 61 kdgrklldll egltgtslpk ergstrvhal nnvnrvlqvl hqnnvelvni ggtdivdgnh 121 kltlgllwsi ilhwqvkdvm kdvmsdlqqt nsekillswv rqttrpysqv n x lnftts \\ t 181 dglafiiavlh rhkpdlfswd kvvkmspier lehafskaqt ylgieklldp edvavqlpdk 241 ksiimyltsl fevlpqqvti dairevetlp rkykkeceee ainiqstape eehespraet 301 pstvtevdmd Idsyqialee vltwllsaed tfqeqddisd dveevkdqfa theafmmelt 361 ahqssvgsvl qagnqlitqg tlsdeeefei qeqmtllnar wealrvesmd rqsrlhdvlm 421 elqkkqlqql sawltlteer iqkmetcpld ddvkslqkll eehkslqsdl eaeqvkvnsl 481 thmvvivden sgesataile dqlqklgerw tavcrwteer wnrlqeinil wqelleeqcl 541 Ikawltekee alnkvqtsnf kdqkelsvsv rrlailkedm emkrqtldql seigqdvgql 601 Idnskaskki nsdseeltqr wdslvqrled ssnqvtqava klgmsqipqk dlletvrvre 661 qaitkkskqe Ippppppkkr qihvaladfn rawteltdwl slldqviksq rvmvgdledi 721 nemiikqkat mqdleqrrpq leelitaaqn Iknktsnqea rtiitdrier iqnqwdevqe 781 hlqnrrqqln emlkdstqwl eakeeaeqvl gqaraklesw kegpytvdai qkkitetkql 841 akdlrqwqtn vdvandlalk llrdysaddt rkvhmiteni naswrsihkr vsereaalee 901 thrllqqfpl dlekflawlt eaetanvlq datrkerlle dskgvkelmk qwqdlqgeie 961 ahtdvyhnld ensqkilrsl egsddavllq rrldnmnfkw selrkkslni rshleatler 1021 Iqelqeatde Idlklrqaev ikgswqpvgd llidslqdhl ekvkalrgei aplkenvshv 1081 ndlarqlttl giqlspynls tledlntrwk llqvavedrv rqlheahrdf gpasqhflst 1141 svqgpwerai spnkvpyyin hetqtcwdh pkmtelyqsl adlnnvrfsa yrtamklrrl 1201 qkalcldlls Isaacdaldq hnlkqndqpm dilqiinclt tiydrleqeh nnlvnvplcv 1261 dmclnwllnv ydtgrtgrir vlsfktgiis Ickahledky rylfkqvass tgfcdqrrlg 1321 lllhdsiqip rqlgevasfg gsniepsvrs cfqfannkpe ieaalfldwm rlepqsmvwl 1381 pvlhrvaaae takhqakcni ckecpiigfr yrslkhfnyd icqscffsgr vakghkmhyp 1441 mveyctptts gedvrdfakv Iknkfrtkry fakhprmgyl pvqtvlegdn met

[0118] SI-trophin_09_AE protein (SEQ ID NO: 3)1 makygeheas pdngqnefsd iiksrsdehn dvqkktftkw inarfsksgk ppindmftdl 61 kdgrklldll egltgtslpk ergstrvhal nnvnrvlqvl hqnnvelvni ggtdivdgnh 121 kltlgllwsi ilhwqvkdvm kdvmsdlqqt nsekillswv rqttrpysqv nvlnfttswt 181 dglafiiavlh rhkpdlfswd kvvkmspier lehafskaqt ylgieklldp edvavqlpdk 241 ksiimyltsl fevlpqqvti dairevetlp rkykkeceee ainiqstape eehespraet 301 pstvtevdmd Idsyqialee vltwllsaed tfqeqddisd dveevkdqfa theafmmelt 361 ahqssvgsvl qagnqlitqg tlsdeeefei qeqmtllnar wealrvesmd rqsrlhdvlm 421 elqkkqlqql sawltlteer iqkmetcpld ddvkslqkll eehkslqsdl eaeqvkvnsl 481 thmvvivden sgesataile dqlqklgerw tavcrwteer wnrlqeinia vaklgmsqip 541 qkdlletvrv reqaitkksk qelppppppk krqihvalad fhrawteltd wlslldqvik 601 sqrvmvgdle dinemiikqk atmqdleqrr pqleelitaa qnlknktsnq eartiitdri 661 eriqnqwdev qehlqnrrqq Inemlkdstq wleakeeaeq vlgqarakle swkegpytvd 721 aiqkkitetk qlakdlrqwq tnvdvandla Ikllrdysad dtrkvhmite ninaswrsih 781 krvsereaal eethrllqqf pldlekflaw Iteaettanv Iqdatrkerl ledskgvkel 841 mkqwqdlqge ieahtdvyhn Idensqkilr slegsddavl Iqrrldnmnf kwselrkksl 901 nirshleatl erlqelqeat deldlklrqa evikgswqpv gdllidslqd hlekvkalrg 961 eiaplkenvs hvndlarqlt tlgiqlspyn Istledlntr wkllqvaved rvrqlheahr 1021 dfgpasqhfl stsvqgpwer aispnkvpyy inhetqttcw dhpkmtelyq sladlnnvrf 1081 sayrtamklr rlqkalcldl Islsaacdal dqhnlkqndq pmdilqiinc Ittiydrleq 1141 ehnnlvnvpl cvdmclnwll nvydtgrtgr irvlsfktgi islckahled kyrylfkqva 1201 sstgfcdqrr Iglllhdsiq iprqlgevas fggsniepsv rscfqfannk peieaalfld 1261 wmrlepqsmv wlpvlhrvaa aetakhqakc nickecpiig fryrslkhfh ydicqscffs1321 grvakghkmh ypmveyctpt tsgedvrdfa kvlknkfrtk ryfakhprmg ylpvqtvleg1381 dnmet

[0119] SI-trophin_07_AE_nucleic acid sequence (SEQ ID NO: 85)ATGGCCAAGTATGGAGAACATGAAGCCAGTCCTGACAATGGGCAGAACGAATTCAGTGATATCATTAAGTCCAGATCTGATGAACACAATGACGTACAGAAGAAAACCTTTACCAAATGGATAAATGCTCGATTTTCAAAGAGTGGGAAACCACCCATCAATGATATGTTCACAGACCTCAAAGATGGAAGGAAGCTATTGGATCTTCTAGAAGGCCTCACAGGAACATCACTGCCAAAGGAACGTGGTTCCACAAGGGTACATGCCTTAAATAACGTCAACAGAGTGCTGCAGGTTTTACATCAGAACAATGTGGAATTAGTGAATATAGGGGGAACTGACATTGTGGATGGAAATCACAAACTGACTTTGGGGTTACTTTGGAGCATCATTTTGCACTGGCAGGTGAAAGATGTCATGAAGGATGTCATGTCGGACCTGCAGCAGACGAACAGTGAGAAGATCCTGCTCAGCTGGGTGCGTCAGACCACCAGGCCCTACAGCCAAGTCAACGTCCTCAACTTCACCACCAGCTGGACAGATGGACTCGCCTTTAATGCTGTCCTCCACCGACATAAACCTGATCTCTTCAGCTGGGATAAAGTTGTCAAAATGTCACCAATTGAGAGACTTGAACATGCCTTCAGCAAGGCTCAAACTTATTTGGGAATTGAAAAGCTGTTAGATCCTGAAGATGTTGCCGTTCAGCTTCCTGACAAGAAATCCATAATTATGTATTTAACATCTTTGTTTGAGGTGCTACCTCAGCAAGTCACCATAGACGCCATCCGTGAGGTAGAGACACTCCCAAGGAAATATAAAAAAGAATGTGAAGAAGAGGCAATTAATATACAGAGTACAGCGCCTGAGGAGGAGCATGAGAGrCCCCGAGCTGAAACrCCCAGCACTGrCACTGAGGTTGACATGGATCTGGACAGCTATCAGATTGCGTTGGAGGAAGTGCTGACCTGGTTGCTTTCTGCTGAGGACACTTTCCAGGAGCAGGATGATATTTCTGATGATGTTGAAGAAGTCAAAGACCAGTTTGCAACCCATGAAGCTTTTATGATGGAACTGACTGCACACCAGAGCAGTGTGGGCAGCGTCCTGCAGGCAGGCAACCAACTGATAACACAAGGAACTCTGTCAGACGAAGAAGAATTTGAGATTCAGGAACAGATGACCCTGCTGAATGCTAGATGGGAGGCTCTTAGGGTGGAGAGTATGGACAGACAGTCCCGGCTGCACGATGTGCTGATGGAACTGCAGAAGAAGCAACTGCAGCAGCTCTCCGCCTGGTTAACACTCACAGAGGAGCGCATTCAGAAGATGGAAACTTGCCCCCTGGATGATGATGTAAAATCTCTACAAAAGCTGCTAGAAGAACATAAAAGTTTGCAAAGTGATCTTGAGGCTGAACAGGTGAAAGTAAATTCACTAACTCACATGGTGGTCATTGTTGATGAAAACAGTGGTGAGAGTGCTACAGCTATCCTAGAAGACCAGTTACAGAAACTTGGTGAGCGCTGGACAGCAGTATGCCGTTGGACTGAAGAACGCTGGAATAGGTTACAAGAAATCAATATAGCTGTAGCAAAGCTGGGGATGTCTCAGATTCCTCAGAAGGACCTTTTGGAGACTGTTCGTGTAAGAGAACAAGCAATTACAAAAAAATCTAAGCAGGAACTGCCTCCTCCTCCTCCCCCAAAGAAGAGACAGATCCATGTGGCTCTGGCAGATTTCAACCGGGCTTGGACAGAACTTACCGACTGGCTTTCTCTGCTTGATCAAGTTATAAAATCACAGAGGGTGATGGTGGGTGACCTTGAGGATATCAACGAGATGATCATCAAGCAGAAGGCAACAATGCAGGATTTGGAACAGAGGCGTCCCCAGTTGGAAGAACTCATTACCGCTGCCCAAAATTTGAAAAACAAGACCAGCAATCAAGAGGCTAGAACAATCATTACGGATCGAATTGAAAGAATTCAGAATCAGTGGGATGAAGTACAAGAACACCTTCAGAACCGGAGGCAACAGTTGAATGAAATGTTAAAGGATTCAACACAATGGCTGGAAGCTAAGGAAGAAGCTGAGCAGGTCTTAGGACAGGCCAGAGCCAAGCTTGAGTCATGGAAGGAGGGTCCCTATACAGTAGATGCAATCCAAAAGAAAATCACAGAAACCAAGCAGTTGGCCAAAGACCTCCGCCAGTGGCAGACAAATGTAGATGTGGCAAATGACTTGGCCCTGAAACTTCTCCGGGATTATTCTGCAGATGATACCAGAAAAGTCCACATGATAACAGAGAATATCAATGCCTCTTGGAGAAGCATTCATAAAAGGGTGAGTGAGCGAGAGGCTGCTTTGGAAGAAACTCATAGATTACTGCAACAGTTCCCCCTGGACCTGGAAAAGTTTCTTGCCTGGCTTACAGAAGCTGAAACAACTGCCAATGTCCTACAGGATGCTACCCGTAAGGAAAGGCTCCTAGAAGACTCCAAGGGAGTAAAAGAGCTGATGAAACAATGGCAAGACCTCCAAGGTGAAATTGAAGCTCACACAGATGTTTATCACAACCTGGATGAAAACAGCCAAAAAATCCTGAGATCCCTGGAAGGTTCCGATGATGCAGTCCTGTTACAAAGACGTTTGGATAACATGAACTTCAAGTGGAGTGAACTTCGGAAAAAGTCTCTCAACATTAGGTCCCATTTGGAAGCCAGTTCTGACCAGTGGAAGCGTCTGCACCTTTCTCTGCAGGAACTTCTGGTGTGGCTACAGCTGAAAGATGATGAATTAAGCCGGCAGGCACCTATTGGAGGCGACTTTCCAGCAGTTCAGAAGCAGAACGATGTACATAGGGCCTTCAAGAGGGAATTGAAAACTAAAGAACCTGTAATCATGAGTACTCTTGAGACTGTACGAATATTTCTGACAGAGCAGCCTTTGGAAGGACTAGAGAAACTCTACCAGGAGCCCAGAGAGCTGCCTCCTGAGGAGAGAGCCCAGAATGTCACTCGGCTTCTACGAAAGCAGGCTGAGGAGGTCAATACTGAGTGGGAAAAATTGAACCTGCACTCCGCTGACTGGCAGAGAAAAATAGATGAGACCCTTGAAAGACTCCGGGAACTTCAAGAGGCCACGGATGAGCTGGACCTCAAGCTGCGCCAAGCTGAGGTGATCAAGGGATCCTGGCAGCCCGTGGGCGATCTCCTCATTGACTCTCTCCAAGATCACCTCGAGAAAGTCAAGGCACTTCGAGGAGAAATTGCGCCTCTGAAAGAGAACGTGAGCCACGTCAATGACCTTGCTCGCCAGCTTACCACTTTGGGCATTCAGCTCTCACCGTATAACCTCAGCACTCTGGAAGACCTGAACACCAGATGGAAGCTTCTGCAGGTGGCCGTCGAGGACCGAGTCAGGCAGCTGCATGAAGCCCACAGGGACTTTGGTCCAGCATCTCAGCACTTTCTTTCCACGTCTGTCCAGGGTCCCTGGGAGAGAGCCATCTCGCCAAACAAAGTGCCCTACTATATCAACCACGAGACTCAAACAACTTGCTGGGACCATCCCAAAATGACAGAGCTCTACCAGTCTTTAGCTGACCTGAATAATGTCAGATTCTCAGCTTATAGGACTGCCATGAAACTCCGAAGACTGCAGAAGGCCCTTTGCTTGGATCTCTTGAGCCTGTCAGCTGCATGTGATGCCTTGGACCAGCACAACCTCAAGCAAAATGACCAGCCCATGGATATCCTGCAGATTATTAATTGTTTGACCACTATTTATGACCGCCTGGAGCAAGAGCACAACAATTTGGTCAACGTCCCTCTCTGCGTGGATATGTGTCTGAACTGGCTGCTGAATGTTTATGATACGGGACGAACAGGGAGGATCCGTGTCCTGTCTTTTAAAACTGGCATCATTTCCCTGTGTAAAGCACATTTGGAAGACAAGTACAGATACCTTTTCAAGCAAGTGGCAAGTTCAACAGGATTTTGTGACCAGCGCAGGCTGGGCCTCCTTCTGCATGATTCTATCCAAATTCCAAGACAGTTGGGTGAAGTTGCATCCTTTGGGGGCAGTAACATTGAGCCAAGTGTCCGGAGCTGCTTCCAATTTGCTAATAATAAGCCAGAGATCGAAGCGGCCCTCTTCCTAGACTGGATGAGACTGGAACCCCAGTCCATGGTGTGGCTGCCCGTCCTGCACAGAGTGGCTGCTGCAGAAACTGCCAAGCATCAGGCCAAATGTAACATCTGCAAAGAGTGTCCAATCATTGGATTCAGGTACAGGAGTCTAAAGCACTTTAATTATGACATCTGCCAAAGCTGCTTTTTTTCTGGTCGAGTTGCAAAAGGCCATAAAATGCACTATCCCATGGTGGAATATTGCACTCCGACTACATCAGGAGAAGATGTTCGAGACTTTGCCAAGGTACTAAAAAACAAATTTCGAACCAAAAGGTATTTTGCGAAGCATCCCCGAATGGGCTACCTGCCAGTGCAGACTGTCTTAGAGGGGGACAACATGGAAACT

[0120] SI-trophin_09 nucleic acid sequence (SEQ ID NO: 86)ATGGCCAAGTATGGAGAACATGAAGCCAGTCCTGACAATGGGCAGAACGAATTCAGTGATATCATTAAGTCCAGATCTGATGAACACAATGACGTACAGAAGAAAACCTTTACCAAATGGATAAATGCTCGATTTTCAAAGAGTGGGAAACCACCCATCAATGATATGTTCACAGACCTCAAAGATGGAAGGAAGCTATTGGATCTTCTAGAAGGCCTCACAGGAACATCACTGCCAAAGGAACGTGGTTCCACAAGGGTACATGCCTTAAATAACGTCAACAGAGTGCTGCAGGTTTTACATCAGAACAATGTGGAATTAGTGAATATAGGGGGAACTGACATTGTGGATGGAAATCACAAACTGACTTTGGGGTTACTTTGGAGCATCATTTTGCACTGGCAGGTGAAAGATGTCATGAAGGATGTCATGTCGGACCTGCAGCAGACGAACAGTGAGAAGATCCTGCTCAGCTGGGTGCGTCAGACCACCAGGCCCTACAGCCAAGTCAACGTCCTCAACTTCACCACCAGCTGGACAGATGGACTCGCCTTTAATGCTGTCCTCCACCGACATAAACCTGATCTCTTCAGCTGGGATAAAGTTGTCAAAATGTCACCAATTGAGAGACTTGAACATGCCTTCAGCAAGGCTCAAACTTATTTGGGAATTGAAAAGCTGTTAGATCCTGAAGATGTTGCCGTTCAGCTTCCTGACAAGAAATCCATAATTATGTATTTAACATCTTTGTTTGAGGTGCTACCTCAGCAAGTCACCATAGACGCCATCCGTGAGGTAGAGACACTCCCAAGGAAATATAAAAAAGAATGTGAAGAAGAGGCAATTAATATACAGAGTACAGCGCCTGAGGAGGAGCATGAGAGTCCCCGAGCTGAAACTCCCAGCACTGTCACTGAGGTTGACATGGATCTGGACAGCTATCAGATTGCGTTGGAGGAAGTGCTGACCTGGTTGCTTTCTGCTGAGGACACTTTCCAGGAGCAGGATGATATTTCTGATGATGTTGAAGAAGTCAAAGACCAGTTTGCAACCCATGAAGCTTTTATGATGGAACTGACTGCACACCAGAGCAGTGTGGGCAGCGTCCTGCAGGCAGGCAACCAACTGATAACACAAGGAACTCTGTCAGACGAAGAAGAATTTGAGATTCAGGAACAGATGACCCTGCTGAATGCTAGATGGGAGGCTCTTAGGGTGGAGAGTATGGACAGACAGTCCCGGCTGCACGATGTGCTGATGGAACTGCAGAAGAAGCAACTGCAGCAGCTCTCCGCCTGGTTAACACTCACAGAGGAGCGCATTCAGAAGATGGAAACTTGCCCCCTGGATGATGATGTAAAATCTCTACAAAAGCTGCTAGAAGAACATAAAAGTTTGCAAAGTGATCTTGAGGCTGAACAGGTGAAAGTAAATTCACTAACTCACATGGTGGTCATTGTTGATGAAAACAGTGGTGAGAGTGCTACAGCTATCCTAGAAGACCAGTTACAGAAACTTGGTGAGCGCTGGACAGCAGTATGCCGTTGGACTGAAGAACGCTGGAATAGGTTACAAGAAATCAATATATTGTGGCAGGAATTATTGGAAGAACAGTGCTTGTTGAAAGCTTGGTTAACCGAAAAAGAAGAGGCTTTAAATAAAGTCCAGACAAGCAACTTCAAAGACCAAAAGGAACTAAGTGTCAGTGTTCGACGTCTGGCTATTTTGAAGGAAGACATGGAAATGAAGCGTCAAACATTGGATCAGCTGAGTGAGATTGGCCAGGATGTGGGACAATTACTTGATAATTCCAAGGCATCTAAGAAGATCAACAGTGACTCAGAGGAACTGACTCAAAGATGGGATTCTTTGGTTCAGAGACTAGAAGATTCCTCCAACCAGGTGACTCAGGCTGTAGCAAAGCTGGGGATGTCTCAGATTCCTCAGAAGGACCTTTTGGAGACTGTTCGTGTAAGAGAACAAGCAATTACAAAAAAATCTAAGCAGGAACTGCCTCCTCCTCCTCCCCCAAAGAAGAGACAGATCCATGTGGCTCTGGCAGATTTCAACCGGGCTTGGACAGAACTTACCGACTGGCTTTCTCTGCTTGATCAAGTTATAAAATCACAGAGGGTGATGGTGGGTGACCTTGAGGATATCAACGAGATGATCATCAAGCAGAAGGCAACAATGCAGGATTTGGAACAGAGGCGTCCCCAGTTGGAAGAACTCATTACCGCTGCCCAAAATTTGAAAAACAAGACCAGCAATCAAGAGGCTAGAACAATCATTACGGATCGAATTGAAAGAATTCAGAATCAGTGGGATGAAGTACAAGAACACCTTCAGAACCGGAGGCAACAGTTGAATGAAATGTTAAAGGATTCAACACAATGGCTGGAAGCTAAGGAAGAAGCTGAGCAGGTCTTAGGACAGGCCAGAGCCAAGCTTGAGTCATGGAAGGAGGGTCCCTATACAGTAGATGCAATCCAAAAGAAAATCACAGAAACCAAGCAGTTGGCCAAAGACCTCCGCCAGTGGCAGACAAATGTAGATGTGGCAAATGACTTGGCCCTGAAACTTCTCCGGGATTATTCTGCAGATGATACCAGAAAAGTCCACATGATAACAGAGAATATCAATGCCTCTTGGAGAAGCATTCATAAAAGGGTGAGTGAGCGAGAGGCTGCTTTGGAAGAAACTCATAGATTACTGCAACAGTTCCCCCTGGACCTGGAAAAGTTTCTTGCCTGGCTTACAGAAGCTGAAACAACTGCCAATGTCCTACAGGATGCTACCCGTAAGGAAAGGCTCCTAGAAGACTCCAAGGGAGTAAAAGAGCTGATGAAACAATGGCAAGACCTCCAAGGTGAAATTGAAGCTCACACAGATGTTTATCACAACCTGGATGAAAACAGCCAAAAAATCCTGAGATCCCTGGAAGGTTCCGATGATGCAGTCCTGTTACAAAGACGTTTGGATAACATGAACTTCAAGTGGAGTGAACTTCGGAAAAAGTCTCTCAACATTAGGTCCCATTTGGAAGCCACCCTTGAAAGACTCCGGGAACTTCAAGAGGCCACGGATGAGCTGGACCTCAAGCTGCGCCAAGCTGAGGTGATCAAGGGATCCTGGCAGCCCGTGGGCGATCTCCTCATTGACTCTCTCCAAGATCACCTCGAGAAAGTCAAGGCACTTCGAGGAGAAATTGCGCCTCTGAAAGAGAACGTGAGCCACGTCAATGACCTTGCTCGCCAGCTTACCACTTTGGGCATTCAGCTCTCACCGTATAACCTCAGCACTCTGGAAGACCTGAACACCAGATGGAAGCTTCTGCAGGTGGCCGTCGAGGACCGAGTCAGGCAGCTGCATGAAGCCCACAGGGACTTTGGTCCAGCATCTCAGCACTTTCTTTCCACGTCTGTCCAGGGTCCCTGGGAGAGAGCCATCTCGCCAAACAAAGTGCCCTACTATATCAACCACGAGACTCAAACAACTTGCTGGGACCATCCCAAAATGACAGAGCTCTACCAGTCTTTAGCTGACCTGAATAATGTCAGATTCTCAGCTTATAGGACTGCCATGAAACTCCGAAGACTGCAGAAGGCCCTTTGCTTGGATCTCTTGAGCCTGTCAGCTGCATGTGATGCCTTGGACCAGCACAACCTCAAGCAAAATGACCAGCCCATGGATATCCTGCAGATTATTAATTGTTTGACCACTATTTATGACCGCCTGGAGCAAGAGCACAACAATTTGGTCAACGTCCCTCTCTGCGTGGATATGTGTCTGAACTGGCTGCTGAATGTTTATGATACGGGACGAACAGGGAGGATCCGTGTCCTGTCTTTTAAAACTGGCATCATTTCCCTGTGTAAAGCACATTTGGAAGACAAGTACAGATACCTTTTCAAGCAAGTGGCAAGTTCAACAGGATTTTGTGACCAGCGCAGGCTGGGCCTCCTTCTGCATGATTCTATCCAAATTCCAAGACAGTTGGGTGAAGTTGCATCCTTTGGGGGCAGTAACATTGAGCCAAGTGTCCGGAGCTGCTTCCAATTTGCTAATAATAAGCCAGAGATCGAAGCGGCCCTCTTCCTAGACTGGATGAGACTGGAACCCCAGTCCATGGTGTGGCTGCCCGTCCTGCACAGAGTGGCTGCTGCAGAAACTGCCAAGCATCAGGCCAAATGTAACATCTGCAAAGAGTGTCCAATCATTGGATTCAGGTACAGGAGTCTAAAGCACTTTAATTATGACATCTGCCAAAGCTGCTTTTTTTCTGGTCGAGTTGCAAAAGGCCATAAAATGCACTATCCCATGGTGGAATATTGCACTCCGACTACATCAGGAGAAGATGTTCGAGACTTTGCCAAGGTACTAAAAAACAAATTTCGAACCAAAAGGTATTTTGCGAAGCATCCCCGAATGGGCTACCTGCCAGTGCAGACTGTCTTAGAGGGGGACAACATGGAAACT

[0121] SI-trophin_09_AE nucleic acid sequence (SEQ ID NO: 87)ATGGCCAAGTATGGAGAACATGAAGCCAGTCCTGACAATGGGCAGAACGAATTCAGTGATATCATTAAGTCCAGATCTGATGAACACAATGACGTACAGAAGAAAACCTTTACCAAATGGATAAATGCTCGATTTTCAAAGAGTGGGAAACCACCCATCAATGATATGTTCACAGACCTCAAAGATGGAAGGAAGCTATTGGATCTTCTAGAAGGCCTCACAGGAACATCACTGCCAAAGGAACGTGGTTCCACAAGGGTACATGCCTTAAATAACGTCAACAGAGTGCTGCAGGTTTTACATCAGAACAATGTGGAATTAGTGAATATAGGGGGAACTGACATTGTGGATGGAAATCACAAACTGACTTTGGGGTTACTTTGGAGCATCATTTTGCACTGGCAGGTGAAAGATGTCATGAAGGATGTCATGTCGGACCTGCAGCAGACGAACAGTGAGAAGATCCTGCTCAGCTGGGTGCGTCAGACCACCAGGCCCTACAGCCAAGTCAACGTCCTCAACTTCACCACCAGCTGGACAGATGGACTCGCCTTTAATGCTGTCCTCCACCGACATAAACCTGATCTCTTCAGCTGGGATAAAGTTGTCAAAATGTCACCAATTGAGAGACTTGAACATGCCTTCAGCAAGGCTCAAACTTATTTGGGAATTGAAAAGCTGTTAGATCCTGAAGATGTTGCCGTTCAGCTTCCTGACAAGAAATCCATAATTATGTATTTAACATCTTTGTTTGAGGTGCTACCTCAGCAAGTCACCATAGACGCCATCCGTGAGGTAGAGACACTCCCAAGGAAATATAAAAAAGAATGTGAAGAAGAGGCAATTAATATACAGAGTACAGCGCCTGAGGAGGAGCATGAGAGTCCCCGAGCTGAAACTCCCAGCACTGTCACTGAGGTTGACATGGATCTGGACAGCTATCAGATTGCGTTGGAGGAAGTGCTGACCTGGTTGCTTTCTGCTGAGGACACTTTCCAGGAGCAGGATGATATTTCTGATGATGTTGAAGAAGTCAAAGACCAGTTTGCAACCCATGAAGCTTTTATGATGGAACTGACTGCACACCAGAGCAGTGTGGGCAGCGTCCTGCAGGCAGGCAACCAACTGATAACACAAGGAACTCTGTCAGACGAAGAAGAATTTGAGATTCAGGAACAGATGACCCTGCTGAATGCTAGATGGGAGGCTCTTAGGGTGGAGAGTATGGACAGACAGTCCCGGCTGCACGATGTGCTGATGGAACTGCAGAAGAAGCAACTGCAGCAGCTCTCCGCCTGGTTAACACTCACAGAGGAGCGCATTCAGAAGATGGAAACTTGCCCCCTGGATGATGATGTAAAATCTCTACAAAAGCTGCTAGAAGAACATAAAAGTTTGCAAAGTGATCTTGAGGCTGAACAGGTGAAAGTAAATTCACTAACTCACATGGTGGTCATTGTTGATGAAAACAGTGGTGAGAGTGCTACAGCTATCCTAGAAGACCAGTTACAGAAACTTGGTGAGCGCTGGACAGCAGTATGCCGTTGGACTGAAGAACGCTGGAATAGGTTACAAGAAATCAATATAGCTGTAGCAAAGCTGGGGATGTCTCAGATTCCTCAGAAGGACCTTTTGGAGACTGTTCGTGTAAGAGAACAAGCAATTACAAAAAAATCTAAGCAGGAACTGCCTCCTCCTCCTCCCCCAAAGAAGAGACAGATCCATGTGGCTCTGGCAGATTTCAACCGGGCTTGGACAGAACTTACCGACTGGCTTTCTCTGCTTGATCAAGTTATAAAATCACAGAGGGTGATGGTGGGTGACCTTGAGGATATCAACGAGATGATCATCAAGCAGAAGGCAACAATGCAGGATTTGGAACAGAGGCGTCCCCAGTTGGAAGAACTCATTACCGCTGCCCAAAATTTGAAAAACAAGACCAGCAATCAAGAGGCTAGAACAATCATTACGGATCGAATTGAAAGAATTCAGAATCAGTGGGATGAAGTACAAGAACACCTTCAGAACCGGAGGCAACAGTTGAATGAAATGTTAAAGGATTCAACACAATGGCTGGAAGCTAAGGAAGAAGCTGAGCAGGTCTTAGGACAGGCCAGAGCCAAGCTTGAGTCATGGAAGGAGGGTCCCTATACAGTAGATGCAATCCAAAAGAAAATCACAGAAACCAAGCAGTTGGCCAAAGACCTCCGCCAGTGGCAGACAAATGTAGATGTGGCAAATGACTTGGCCCTGAAACTTCTCCGGGATTATTCTGCAGATGATACCAGAAAAGTCCACATGATAACAGAGAATATCAATGCCTCTTGGAGAAGCATTCATAAAAGGGTGAGTGAGCGAGAGGCTGCTTTGGAAGAAACTCATAGATTACTGCAACAGTTCCCCCTGGACCTGGAAAAGTTTCTTGCCTGGCTTACAGAAGCTGAAACAACTGCCAATGTCCTACAGGATGCTACCCGTAAGGAAAGGCTCCTAGAAGACTCCAAGGGAGTAAAAGAGCTGATGAAACAATGGCAAGACCTCCAAGGTGAAATTGAAGCTCACACAGATGTTTATCACAACCTGGATGAAAACAGCCAAAAAATCCTGAGATCCCTGGAAGGTTCCGATGATGCAGTCCTGTTACAAAGACGTTTGGATAACATGAACTTCAAGTGGAGTGAACTTCGGAAAAAGTCTCTCAACATTAGGTCCCATTTGGAAGCCACCCTTGAAAGACTCCGGGAACTTCAAGAGGCCACGGATGAGCTGGACCTCAAGCTGCGCCAAGCTGAGGTGATCAAGGGATCCTGGCAGCCCGTGGGCGATCTCCTCATTGACTCTCTCCAAGATCACCTCGAGAAAGTCAAGGCACTTCGAGGAGAAATTGCGCCTCTGAAAGAGAACGTGAGCCACGTCAATGACCTTGCTCGCCAGCTTACCACTTTGGGCATTCAGCTCTCACCGTATAACCTCAGCACTCTGGAAGACCTGAACACCAGATGGAAGCTTCTGCAGGTGGCCGTCGAGGACCGAGTCAGGCAGCTGCATGAAGCCCACAGGGACTTTGGTCCAGCATCTCAGCACTTTCTTTCCACGTCTGTCCAGGGTCCCTGGGAGAGAGCCATCTCGCCAAACAAAGTGCCCTACTATATCAACCACGAGACTCAAACAACTTGCTGGGACCATCCCAAAATGACAGAGCTCTACCAGTCTTTAGCTGACCTGAATAATGTCAGATTCTCAGCTTATAGGACTGCCATGAAACTCCGAAGACTGCAGAAGGCCCTTTGCTTGGATCTCTTGAGCCTGTCAGCTGCATGTGATGCCTTGGACCAGCACAACCTCAAGCAAAATGACCAGCCCATGGATATCCTGCAGATTATTAATTGTTTGACCACTATTTATGACCGCCTGGAGCAAGAGCACAACAATTTGGTCAACGTCCCTCTCTGCGTGGATATGTGTCTGAACTGGCTGCTGAATGTTTATGATACGGGACGAACAGGGAGGATCCGTGTCCTGTCTTTTAAAACTGGCATCATTTCCCTGTGTAAAGCACATTTGGAAGACAAGTACAGATACCTTTTCAAGCAAGTGGCAAGTTCAACAGGATTTTGTGACCAGCGCAGGCTGGGCCTCCTTCTGCATGATTCTATCCAAATTCCAAGACAGTTGGGTGAAGTTGCATCCTTTGGGGGCAGTAACATTGAGCCAAGTGTCCGGAGCTGCTTCCAATTTGCTAATAATAAGCCAGAGATCGAAGCGGCCCTCTTCCTAGACTGGATGAGACTGGAACCCCAGTCCATGGTGTGGCTGCCCGTCCTGCACAGAGTGGCTGCTGCAGAAACTGCCAAGCATCAGGCCAAATGTAACATCTGCAAAGAGTGTCCAATCATTGGATTCAGGTACAGGAGTCTAAAGCACTTTAATTATGACATCTGCCAAAGCTGCTTTTTTTCTGGTCGAGTTGCAAAAGGCCATAAAATGCACTATCCCATGGTGGAATATTGCACTCCGACTACATCAGGAGAAGATGTTCGAGACTTTGCCAAGGTACTAAAAAACAAATTTCGAACCAAAAGGTATTTTGCGAAGCATCCCCGAATGGGCTACCTGCCAGTGCAGACTGTCTTAGAGGGGGACAACATGGAAACTAGGCCTAATAAAGAGCTCAGATGCATC GATCAGAGTGTGTTGGTTTTTTGTGTG

[0122] In some embodiments of any of the aspects, the polypeptide is engineered. In some embodiments of any of the aspects, the poly peptide is chimeric. In some embodiments of any of the aspects, the polypeptide is not a naturally -occuring polypeptide.

[0123] In some embodiments of any of the aspects, the polypeptide has less than 95% sequence identity to wild-type dystrophin (e.g., SEQ ID NO: 30). In some embodiments of any of the aspects, the polypeptide has less than 90% sequence identity to wild-type dystrophin (e.g., SEQ ID NO: 30). In some embodiments of any of the aspects, the polypeptide has less than 80% sequence identity to wild-type dystrophin (e.g., SEQ ID NO: 30). In some embodiments of any of the aspects, the polypeptide has less than 70% sequence identity to wild-type dystrophin (e.g.. SEQ ID NO: 30). Insome embodiments of any of the aspects, the polypeptide has less than 60% sequence identity’ to wildtype dystrophin (e.g., SEQ ID NO: 30).

[0124] In some embodiments of any of the aspects, the polypeptide has less than 95% sequence identity to dystrophin isoform Dp427m (e.g., SEQ ID NO: 668). In some embodiments of any of the aspects, the polypeptide has less than 90% sequence identity to dystrophin isoform Dp427m (e.g., SEQ ID NO: 668). In some embodiments of any of the aspects, the polypeptide has less than 80% sequence identity to dystrophin isoform Dp427m (e.g.. SEQ ID NO: 668). In some embodiments of any of the aspects, the polypeptide has less than 70% sequence identity to dystrophin isoform Dp427m (e.g.. SEQ ID NO: 668). In some embodiments of any of the aspects, the polypeptide has less than 60% sequence identity to dystrophin isofonn Dp427m (e.g.. SEQ ID NO: 668).

[0125] SEQ ID NO: 668. Dystrophin isoform Dp427m [Homo sapiens]; NCBI ref seq: NP_0039971 mlwweevedc yeredvqkkt ftkwvnaqfs kfgkqhienl fsdlqdgrrl Idllegltgq 61 klpkekgstr vhalnnvnka Irvlqnnnvd Ivnigstdiv dgnhkltlgl iwniilhwqv 121 knvmknimag Iqqtnsekil Iswvrqstrn ypqvnvinft tswsdglaln alihshrpdl 181 fdwnsvvcqq satqrlehaf niaryqlgie klldpedvdt typdkksilm yitslfqvlp 241 qqvsieaiqe vemlprppkv tkeehfqlhh qmhysqqitv slaqgyerts spkprfksya 301 ytqaayvtts dptrspfpsq hleapedksf gsslmesevn Idrvqtalec vlswllsaed 361 tlqaqgeisn dvevvkdqfh thegyrmndlt ahqgrvgnil qlgskligtg klsedeetev 421 qeqmnllnsr weclrvasme kqsnlhrvhn dlqnqklkel ndwltkteer trkmeeeplg 481 pdledlkrqv qqhkvlqedl eqeqvrvnsl thmwvvdes sgdhataale eqlkvlgdrw 541 anicrwtedr wvllqdillk wqrlteeqcl fsawlseked avnkihttgf kdqnemlssl 601 qklavlkadl ekkkqsmgkl yslkqdllst Iknksvtqkt eawldnfarc wdnlvqklek 661 staqisqavt ttqpsltqtt vmetvttvtt reqilvkhaq eelpppppqk krqitvdsei 721 rkrldvdite Ihswitrsea vlqspefaif rkegnfsdlk ekvnaierek aekfrklqda 781 srsaqalveq mvnegvnads ikqaseqlns rwiefcqlls erlnwleyqn niiafynqlq 841 qleqmtttae nwlkiqpttp septaiksql kickdevnrl sdlqpqierl kiqsialkek 901 gqgpmfldad fvaftnhfkq vfsdvqarek elqtifdtlp pmryqetmsa irtwvqqset 961 klsipqlsvt dyeimeqrlg elqalqsslq eqqsglyyls ttvkemskka pseisrky qs 1021 efecicgrwk klssqlvehc qkleeqmnkl rkiqnhiqtl kkwmaevdvf Ikeewpalgd 1081 seilkkqlkq crllvsdiqt iqpslnsvne ggqkikneae pefasrlete Ikelntqwdh 1141 mcqqvyarke alkgglektv slqkdlsemh ewmtqaeeey lerdfeyktp delqkaveem 1201 krakeeaqqk eakvklltes vnsviaqapp vaqealkkel etlttnyqwl ctrlngkckt 1261 leevwacwhe llsylekank wlnevefklk ttenipggae eisevldsle nlmrhsednp 1321 nqirilaqtl tdggvmdeli neeletfnsr wrelheeavr rqklleqsiq saqetekslh 1381 liqesltfid kqlaayiadk vdaaqmpqea qkiqsdltsh eisleemkkh nqgkeaaqrv1441 Isqidvaqkk Iqdvsmkfrl fqkpanfcqr Iqcskmildc vkmhlpalct ksvcqcwqs 1501 qlnhcvnlyk slsevkseve mviktgrqiv qkkqtenpke Idervtalkl hynelgakvt 1561 erkqqlekcl klsrkmrkem nvltewlaat dmeltkrsav egmpsnldse vawgkatqke 1621 iekqkvlilks itevgealkt vlgkketlve dklsllnsnw iavtsraeew Inllleyqkh 1681 metfdqnvdh itkwiiqadt lldesekkkp qqkedvlkrl kaelndirpk vdstrdqaan 1741 Imanrgdlicr klvepqisel nhrfaaishr iktgkasipl keleqfnsdi qkllepleae 1801 iqqgvnlkee dfnkdmnedn egtvkellqr gdnlqqritd erkreeikik qqllqtklina 1861 Ikdlrsqrrk kaleishqwy qykrqaddll kclddiekkl aslpeprder kikeidrelq 1921 kkkeelnavr rqaeglsedg aamaveptqi qlskrwreie skfaqfrrln faqihtvree 1981 tmmvmtedmp leisyvpsty Iteithvsqa lleveqllna pdlcakdfed Ifkqeeslkn 2041 ikdslqqssg ridiihskkt aalqsatpve rvklqealsq Idfqwekvnk mykdrqgrfd 2101 rsvekwrrfh ydikifnqwl teaeqflrkt qipenwehak ykwylkelqd gigqrqtwr 2161 tlnatgeeii qqssktdasi Iqeklgslnl rwqevckqls drkkrleeqk nilsefqrdl 2221 nefvlwleea dniasiplep gkeqqlkekl eqvkllveel plrqgilkql netggpvlvs 2281 apispeeqdk lenklkqtnl qwikvsralp ekqgeieaqi kdlgqlekkl edleeqlnhl 2341 llwlspimq leiynqpnqe gpfdvketei avqakqpdve eilskgqhly kekpatqpvk2401 rkledlssew kavnrllqel rakqpdlapg Ittigasptq tvtlvtqpw tketaiskle 2461 mpsslmlevp aladfnrawt eltdwlslld qviksqrvmv gdledinemi ikqkatmqdl 2521 eqrrpqleel itaaqnlknk tsnqeartii tdrieriqnq wdevqehlqn rrqqlnemlk 2581 dstqwleake eaeqvlgqar akleswkegp ytvdaiqkki tetkqlakdl rqwqtnvdva 2641 ndlalkllrd ysaddtrkvh miteninasw rsihkrvser eaaleethrl Iqqfpldlek 2701 flawlteaet tanvlqdatr kerlledskg vkelmkqwqd Iqgeieahtd vvhnldensq 2761 kilrslegsd davllqrrld nmnfkwselr kkslnirshl eassdqwkrl hlslqellvw 2821 Iqlkddelsr qapiggdfpa vqkqndvhra fkrelktkep vimstletvr iflteqpleg 2881 leklyqepre Ippeeraqnv trllrkqaee vnteweklnl hsadwqrkid etlerlrelq 2941 eatdeldlkl rqaevikgsw qpvgdllids Iqdhlekvka Irgeiaplke nvshvndlar 3001 qlttlgiqls pynlstledl ntrwkllqva vedrvrqlhe ahrdfgpasq hflstsvqgp 3061 weraispnkv pyyinlietqt tcwdhpkmte lyqsladlnn vrfsayrtam klrrlqkalc 3121 Idllslsaac daldqhnlkq ndqpmdilqi inclttiydr leqehiinlvn vplcvdmcln 3181 wllnvydtgr tgrirvlsfk tgiislckah ledkyrylfk qvasstgfcd qrrlglllhd 3241 siqiprqlge vasfggsnie psvrscfqfa rmkpeieaal fldwmrlepq smvwlpvlhr 3301 vaaaetakhq akcnickecp iigfryrslk lifnydicqsc ffsgrvakgh kmhypmveyc 3361 tpttsgedvr dfakvlknkf rtkryfakhp rmgylpvqtv Icgdnmctpv tlinfwpvds 3421 apasspqlsh ddthsriehy asrlaemens ngsylndsis pnesiddehl liqhycqsln 3481 qdsplsqprs paqilisles eergeleril adleeenrnl qaeydrlkqq hehkglsplp 3541 sppemmptsp qsprdaelia eakllrqhkg rlearmqile dhnkqlesql hrlrqlleqp3601 qacakvngtt vsspstslqr sdssqpmllr vvgsqtsdsm gccdllsppq dtstglccvm3661 eqlnnsfpss rgmtpgkpm redtm

[0126] In some embodiments of any of the aspects, the polypeptide has less than 95% sequence identity to wild-type utrophin (e.g., SEQ ID NO: 31). In some embodiments of any of the aspects, the polypeptide has less than 90% sequence identity to wild-type utrophin (e.g.. SEQ ID NO: 31). In some embodiments of any of the aspects, the polypeptide has less than 80% sequence identity to wildtype utrophin (e.g., SEQ ID NO: 31). In some embodiments of any of the aspects, the polypeptide has less than 70% sequence identity to wild-ty pe utrophin (e.g., SEQ ID NO: 31). In some embodiments of any of the aspects, the polypeptide has less than 60% sequence identity to wild-type utrophin (e.g.,SEQ ID NO: 31).

[0127] SEQ ID NO: 311 makygeheas pdngqnefsd iiksrsdehn dvqkktftkw inarfsksgk ppindmftdl61 kdgrklldll egltgtslpk ergstrvhal nnvnrvlqvl hqnnvelvni ggtdivdgnh 121 kltlgllwsi ilhwqvkdvm kdvmsdlqqt nsekillswv rqttrpysqv nvlnfttswt 181 dglafnavlh rhkpdlfswd kvvkmspier lehafskaqt ylgieklldp edvavqlpdk 241 ksiimyltsl fevlpqqvti dairevetlp rkykkeceee ainiqstape eehespraet 301 pstvtevdmd Idsyqialee vltwllsaed tfqeqddisd dveevkdqfa theafmmelt 361 ahqssvgsvl qagnqlitqg tlsdeeefei qeqmtllnar wealrvesmd rqsrlhdvlm 421 elqkkqlqql sawltlteer iqkmetcpld ddvkslqkll eehkslqsdl eaeqvkvnsl 481 thmwivden sgesataile dqlqklgerw tavcrwteer wnrlqeinil wqelleeqcl 541 Ikawltekee alnkvqtsnf kdqkelsvsv rrlailkedm emkrqtldql seigqdvgql 601 Idnskaskki nsdseeltqr wdslvqrled ssnqvtqava klgmsqipqk dlletvrvre 661 qaitkkskqe Ippppppkkr qihvdieakk kfdaisaell nwilkwktai qtteikeymk 721 mqdtsemkkk Ikalekeqre ripradelnq tgqilveqmg keglpteeik nvlekvssew 781 knvsqhledl erkiqlqedi nayfkqldel ekviktkeew vkhtsisess rqslpslkds 841 cqreltnllg Ihpkiemara scsalmsqps apdfvqrgfd sflgryqavq eavedrqqhl 901 enelkgqpgh ayletlktlk dvlndsenka qvslnvlndl akvekalqek ktldeilenq 961 kpalhklaee tkaleknvhp dveklykqef ddvqgkwnkl kvlvskdlhl leeialtlra 1021 feadstviek wmdgvkdflm kqqaaqgdda glqrqldqcs afvneietie sslknmkeie 1081 tnlrsgpvag iktwvqtrlg dyqtqlekls keiatqksrl sesqekaanl kkdlaemqew 1141 mtqaeeeyle rdfeykspee lesaveemkr akedvlqkev rvkilkdnik llaakvpsgg 1201 qeltselnw lenyqllcnr irgkchtlee vwscwiellh yldlettwln tleermkste 1261 vlpektdavn ealeslesvl rhpadnrtqi relgqtlidg gilddiisek leafnsryed 1321 Ishlaeskqi slekqlqvlr etdqmlqvlq eslgeldkql ttyltdrida fqvpqeaqki 1381 qaeisahelt leelrrnmrs qpltspesrt arggsqmdvl qrklrevstk fqlfqkpanf 1441 eqrmldckrv Idgvkaelhv Idvkdvdpdv iqthldkcmk lyktlsevkl evetviktgr 1501 hivqkqqtdn pkgmdeqlts Ikvlyndlga qvtegkqdle rasqlarkmk keaaslsewl 1561 satetelvqk stsegllgdl dteiswaknv Ikdlekrkad Intitessaa Iqnliegsep 1621 ileerlcvln agwsrvrtwt edwcntlmnh qnqleifdgn vahistwlyq aealldeiek 1681 kptskqeeiv krlvseldda nlqvenvrdq alilmnargs ssrelvepkl aelnrnfekv 1741 sqhiksakll iaqeplyqcl vttetfetgv pfsdleklen dienmlkfve khlessdede 1801 kmdeesaqie evlqrgeeml hqpmednkke kirlqllllh trynkikaip iqqrkmgqla 1861 sgirssllpt dylveinkil Icmddvelsl nvpelntaiy edfsfqedsl knikdqldkl 1921 geqiavihek qpdvileasg peaiqirdtl tqlnakwdri nrmysdrkgc fdrameewrq 1981 fhcdlndltq witeaeellv dtcapggsld lekarihqqe levgisshqp sfaalnrtgd 2041 givqklsqad gsflkeklag Inqrwdaiva evkdrqprlk geskqvmkyr hqldeiicwl 2101 tkaehamqkr sttelgenlq elrdltqeme vhaeklkwln rtelemlsdk slslperdki 2161 seslrtvnmt wnkicrevpt tlkeciqeps svsqtriaah pnvqkvvlvs sasdipvqsh 2221 rtseisipad Idktitelad wlvlidqmlk snivtvgdve einktvsrmk itkadleqrh 2281 pqldyvftla qnlknkasss dmrtaitekl ervknqwdgt qhgvelrqqq ledmiidslq 2341 wddhreetee Imrkyearly ilqqarrdpl tkqisdnqil Iqelgpgdgi vmafdnvlqk 2401 lleeygsddt rnvketteyl ktswinlkqs iadrqnalea ewrtvqasrr dlenflkwiq 2461 eaettvnvlv dashrenalq dsilarelkq qmqdiqaeid ahndifksid gnrqkmvkal2521 gnseeatmlq hrlddmnqrw ndlkaksasi rahleasaek wnrllmslee likwlnmkde 2581 elkkqmpigg dvpalqlqyd hckalrrelk ekeysvlnav dqarvfladq pieapeeprr 2641 nlqskteltp eeraqkiaka mrkqssevke kweslnavts nwqkqvdkal eklrdlqgam 2701 ddldadmkea esvrngwkpv gdllidslqd hiekimafre eiapinfkvk tvndlssqls 2761 pldlhpslkm srqlddlnmr wkllqvsvdd rlkqlqeahr dfgpssqhfl stsvqlpwqr 2821 sishnkvpyy inhqtqttcw dhpkmtelfq sladlnnvrf sayrtaikir rlqkalcldl 2881 lelsttneif kqhklnqndq llsvpdvinc Itttydgleq mhkdlvnvpl cvdmclnwll 2941 nvydtgrtgk irvqslkigl mslskgllee kyrylfkeva gptemcdqrq Iglllhdaiq 3001 iprqlgevaa fggsniepsv rscfqqnnnk peisvkefid wmhlepqsmv wlpvlhrvaa 3061 aetakhqakc nickecpivg fryrslkhfn ydvcqscffs grtakghklh ypmveycipt 3121 tsgedvrdft kvlknkfrsk kyfakhprlg ylpvqtvleg dnletpitli smwpehydps 3181 qspqlfhddt hsrieqyatr laqmertngs fltdsssttg svedehaliq qycqtlgges 3241 pvsqpqspaq ilksvereer geleriiadl eeeqrnlqve yeqlkdqhlr rglpvgsppe 3301 siisphhtse dseliaeakl Irqhkgrlea rmqiledhnk qlesqlhrlr qlleqpesds 3361 ringvspwas pqhsalsysl dpdasgpqfh qaagedllap phdtstdlte vmeqihstfp 3421 sccpnvpsrp qam

[0128] In some embodiments of any of the aspects, the polypeptide does not comprise any of dystrophin SLR4-SLR19 domains. In some embodiments of any of the aspects, the polypeptide does not comprise any of utrophin SLR4-SLR19 domains. In some embodiments of any of the aspects, the polypeptide does not comprise a dystrophin hinge 3 domain. In some embodiments of any of the aspects, the polypeptide does not comprise a utrophin hinge 3 domain.

[0129] In some embodiments of any of the aspects, the polypeptide does not comprise any of: dystrophin SLR4-SLR19 domains; utrophin SLR4-SLR19 domains; a dystrophin hinge 3 domain; and a utrophin hinge 3 domain.

[0130] In some embodiments of any of the aspects, the polypeptide does not comprise any of: a dystrophin NT domain, a dystrophin hinge 1 domain, a dystrophin SLR1 domain, and a dystrophin SLR2 domain.

[0131] In some embodiments of any of the aspects, the polypeptide docs not comprise any of: a dystrophin NT domain, a dystrophin hinge 1 domain, a dystrophin SLR1 domain, a dystrophin SLR2 domain; and a dystrophin hinge 2 domain.

[0132] In some embodiments of any of the aspects, the polypeptide does not comprise any of: a dystrophin NT domain, a dystrophin hinge 1 domain, a dystrophin SLR1 domain, a dystrophin SLR2 domain; and a dystrophin hinge 3 domain.

[0133] In some embodiments of any of the aspects, the polypeptide does not comprise any of: a dystrophin NT domain and a dystrophin hinge 1 domain.

[0134] In some embodiments of any of the aspects, the polypeptide does not comprise any of: a utrophin SLR18 domain; a utrophin SLR19 domain; a utrophin SLR20 domain; a utrophin SLR21 domain; a utrophin SLR22 domain; a utrophin hinge 4 domain; and a utrophin CR domain.

[0135] In some embodiments of any of the aspects, the polypeptide does not comprise a polypeptide encoded by any of: SEQ ID NO: 600-603. In some embodiments of any of the aspects, the nuclec acid does not comprise any of: SEQ ID NO: 600-603.

[0136] In some embodiments of any of the aspects, the polypeptide docs not comprise a polypeptide encoded by SEQ ID NO: 600. In some embodiments of any of the aspects, the nuclec acid does not comprise SEQ ID NO: 600. In some embodiments of any of the aspects, the polypeptide does not comprise a polypeptide encoded by SEQ ID NO: 601. In some embodiments of any of the aspects, the nuclec acid does not comprise SEQ ID NO: 601. In some embodiments of any of the aspects, the polypeptide does not comprise a polypeptide encoded by SEQ ID NO: 602. In some embodiments of any of the aspects, the nuclec acid does not comprise SEQ ID NO: 602. In some embodiments of any of the aspects, the polypeptide does not comprise a polypeptide encoded by SEQ ID NO: 603. In some embodiments of any of the aspects, the nuclec acid does not comprise SEQ ID NO: 603.

[0137] SEQ ID NO: 600ATGCTTTGGTGGGAGGAAGTGGAGGACTGCTACGAGAGAGAGGACGTGCAGAAGAAAA CCTTCACCAAGTGGGTGAACGCCCAGTTCAGCAAGTTCGGCAAGCAGCACATCGAGAAC CTGTTCAGCGACCTGCAGGATGGCAGGAGACTGCTGGACCTGCTGGAGGGCCTGACCGG CCAGAAGCTGCCCAAGGAGAAGGGCAGCACCAGAGTGCACGCCCTGAACAACGTGAAC AAGGCCCTGAGAGTGCTGCAGAACAACAACGTGGACCTGGTGAACATCGGCAGCACCGA CATCGTGGACGGCAACCACAAGCTGACCCTGGGCCTGATCTGGAACATCATCCTGCACTG GCAGGTGAAGAACGTGATGAAGAACATCATGGCCGGCCTGCAGCAGACCAACAGCGAG AAGATCCTGCTGAGCTGGGTGAGGCAGAGCACCAGAAACTACCCCCAGGTGAACGTGAT CAACTTCACCACCTCCTGGAGCGACGGCCTGGCCCTGAACGCCCTGATCCACAGCCACAG ACCCGACCTGTTCGACTGGAACAGCGTGGTGTGTCAGCAGAGCGCCACCCAGAGACTGG AGCACGCCTTCAACATCGCCAGATACCAGCTGGGCATCGAGAAGCTGCTGGACCCCGAG GACGTGGACACCACCTACCCCGACAAGAAAAGCATCCTCATGTACATTACCAGCCTGTTC CAGGTGCTGCCCCAGCAGGTGTCCATCGAGGCCATCCAGGAAGTGGAAATGCTGCCCAG GCCCCCCAAAGTGACCAAGGAGGAGCACTTCCAGCTGCACCACCAGATGCACTACAGCC AGCAGATCACAGTGAGCCTGGCCCAGGGCTATGAGAGAACCAGCAGCCCCAAGCCCAGA TTCAAGAGCTACGCCTACACCCAGGCCGCCTACGTGACCACCTCCGACCCCACCAGAAG CCCCTTCCCCAGCCAGCACCTGGAGGCCCCCGAGGACAAGAGCTTCGGCAGCAGCCTGA TGGAGAGCGAAGTGAACCTGGACAGATACCAGACCGCCCTGGAGGAAGTGCTGTCCTGG CTGCTGAGCGCCGAGGACACCCTGCAGGCCCAGGGCGAGATCAGCAACGACGTGGAAGT GGTGAAGGACCAGTTCCACACCCACGAGGGCTACATGATGGATCTGACCGCCCACCAGG GCAGAGTGGGCAATATCCTGCAGCTGGGCAGCAAGCTGATCGGCACCGGCAAGCTGAGC GAGGACGAGGAGACCGAAGTGCAGGAGCAGATGAACCTGCTGAACAGCAGATGGGAGT GCCTGAGAGTGGCCAGCATGGAGAAGCAGAGCAACCTGCACAGAGTGCTGATGGACCTG CAGAACCAGAAGCTGAAGGAGCTGAACGACTGGCTGACCAAGACCGAGGAGCGGACCA GAAAGATGGAGGAGGAGCCCCTGGGCCCCGACCTGGAGGACCTGAAGAGACAGGTGCA GCAGCACAAAGTGCTGCAGGAGGACCTGGAGCAGGAGCAGGTGCGCGTGAACAGCCTGACCCACATGGTGGTGGTCGTGGACGAGAGCAGCGGCGACCACGCCACAGCCGCCCTGGAAGAGCAGCTGAAAGTGCTGGGCGACAGATGGGCCAATATTTGTAGGTGGACCGAGGACAGATGGGTGCTGCTGCAGGACCAGCCCGACCTGGCCCCTGGCCTGACCACCATCGGCGCCAGCCCCACCCAGACCGTGACCCTGGTGACCCAGCCCGTGGTGACAAAGGAGACCGCCATCAGCAAGCTGGAGATGCCCAGCTCCCTGATGCTGGAAGTGCCCACCCACCGCCTGCTCCAGCAGTTCCCCCTGGACCTGGAGAAGTTCCTGGCCTGGCTGACCGAGGCCGAAACCACCGCCAATGTGCTCCAGGACGCCACTAGAAAGGAGAGGCTGCTGGAGGACAGCAAGGGCGTGAAAGAGCTGATGAAGCAGTGGCAGGATCTGCAGGGCGAAATCGAGGCCCACACCGACGTGTACCACAACCTGGACGAGAACAGCCAGAAGATTCTGAGGAGCCTGGAGGGCAGCGACGACGCCGTCCTGCTCCAGAGGAGGCTGGACAACATGAACTTCAAGTGGAGCGAGCTGCGGAAGAAGAGCCTGAACATCCGGAGCCACCTGGAAGCCAGCAGCGACCAGTGGAAGAGACTGCACCTGAGCCTGCAGGAGCTGCTGGTGTGGCTGCAGCTGAAGGACGACGAGCTGAGCAGACAGGCCCCCATCGGCGGCGACTTCCCCGCCGTGCAGAAGCAGAACGACGTGCACCGGGCCTTCAAGAGGGAGCTGAAAACCAAGGAACCCGTGATCATGAGCACCCTGGAGACAGTGCGGATCTTCCTGACCGAGCAGCCCCTGGAGGGACTGGAGAAGCTGTACCAGGAGCCCAGAGAGCTGCCCCCCGAGGAGAGAGCCCAGAACGTGACCAGGCTGCTGAGAAAGCAGGCCGAGGAAGTGAATACCGAGTGGGAGAAGCTGAATCTGCACAGCGCCGACTGGCAGAGAAAGATCGACGAGACCCTGGAGAGACTCCAGGAACTGCAGGAAGCCACCGACGAGCTGGACCTGAAGCTGAGACAGGCCGAAGTGATCAAGGGCAGCTGGCAGCCTGTGGGCGATCTGCTGATCGACTCCCTGCAGGATCACCTGGAGAAAGTGAAGGCCCTGCGGGGCGAGATCGCCCCCCTGAAGGAGAATGTGAGCCACGTGAACGACCTGGCCAGACAGCTGACCACCCTGGGCATCCAGCTGAGCCCCTACAACCTGAGCACACTGGAGGATCTGAACACCCGGTGGAAACTGCTGCAGGTGGCCGTGGAGGATAGAGTGAGGCAGCTGCACGAAGCCCACAGAGACTTCGGCCCTGCCTCCCAGCACTTCCTGAGCACCAGCGTGCAGGGCCCCTGGGAGAGAGCCATCTCCCCCAACAAAGTGCCCTACTACATCAACCACGAGACCCAGACCACCTGCTGGGACCACCCTAAGATGACCGAGCTGTATCAGAGCCTGGCCGACCTGAACAATGTGCGGTTCAGCGCCTACAGAACCGCCATGAAGCTGCGGAGACTGCAGAAGGCCCTGTGCCTGGATCTGCTGAGCCTGAGCGCCGCCTGCGACGCCCTGGACCAGCACAACCTGAAGCAGAATGACCAGCCCATGGACATCCTGCAGATCATCAACTGCCTGACCACAATCTACGACCGGCTGGAACAGGAGCACAACAACCTGGTGAATGTGCCCCTGTGCGTGGACATGTGCCTGAATTGGCTGCTGAACGTGTACGACACCGGCAGGACCGGCAGAATCCGCGTGCTGAGCTTCAAGACCGGCATCATCAGCCTGTGCAAGGCCCACCTGGAGGATAAGTACCGCTACCTGTTCAAGCAGGTGGCCAGCAGCACCGGCTTCTGCGATCAGAGGAGACTGGGCCTGCTGCTGCACGATAGCATCCAGATCCCTAGGCAGCTGGGCGAAGTGGCCAGCTTTGGCGGCAGCAACATCGAGCCCTCTGTGAGGAGCTGCTTCCAGTTCGCCAACAACAAGCCCGAGATCGAGGCCGCCCTGTTCCTGGACTGGATGAGGCTGGAGCCTCAGAGCATGGTGTGGCTGCCTGTGCTGCACAGAGTGGCCGGCGGCGAGACCGGCAAGGACCAGGGCAAGTGCAATATCTGGAAGGAGTGCCCCATCATCGGCTTCCGGTACAGGAGCCTGAAGCACTTCAACTACGACATCTGCCAGAGCTGCTTTTTCAGCGGCAGAGTGGCCAAGGGCCACAAAATGCACTACCCCATGGTGGAGTACTGCACCCCCACCACCTCCGGGGAGGATGTGAGAGACTTCGCCAAAGTGGTGAAGAATAAGTTCCGGACCAAGCGGTACTTTGCCAAGCACCCCAGGATGGGGTACCTGCCCGTGCAGACCGTGGTGGAAGGCGACAACATGGAGACCTGA

[0138] SEQ ID NO: 601ATGGCCAAGTATGGGGACCTTGAAGCCAGGCCTGATGATGGGCAGAACGAATTCAGTGACATCATTAAGTCCAGATCTGATGAACACAATGATGTACAGAAGAAAACCTTTACCAAATGGATAAACGCTCGATTTTCCAAGAGTGGGAAACCACCCATCAGTGATATGTTCTCAGACCTCAAAGATGGGAGAAAGCTCTTGGATCTTCTCGAAGGCCTCACAGGAACATCATTGCCAAAGGAACGTGGTTCCACAAGGGTGGATGGCTTAAACAATGTCAACCGAGTGCTACAGGTTTTACATCAGAACAATGTGGACTTGGTGAATATTGGAGGCACGGACATTGTGGATGGAAATCCCAAGGTGACTTTAGGGTTACTCTGGAGCATCATTCTGCACTGGGAGGTGAAGGATGTCATGAAAGATATCATGTCAGACCTGCAGGAGACAAACAGCGAGAAGATCCTGCTGAGCTGGGTGCGGGAGACCACCAGGGCCTACAGTCAAGTCAACGTCCTCAACTTCACCACCAGCTGGACCGATGGACTCGGGTTCAACGCCGTGCTCCACCGGCACAAACCAGATCTCTTCAGCTGGGACAGAGTGGTCAAAATGTCCCCAATTGAGAGACTTGAACATGCTTTTAGCAAGGCCCACACTTATTTGGGAATTGAAAAGCTTCTAGATCCTGAAGATGTTGCTGTGCATCTCCCTGACAAGAAATCCATAATTATGTATTTAACGTCTCTGTTTGAGGTGGTTCCTCAGGAAGTCACGATAGATGGCATCCGAGAGGTGGAGACTCTCCCAAGGAAGTATAAGAAAGAATGTGAAGAGGAAGAAATTCATATCCAGAGTGCAGTGCTGGGAGAGGAAGGCCAGAGTCCCCGAGGTGAGACCCCTAGCACCGTCACTGAAGTGGACATGGATTTGGACAGGTACCAGATAGCGGTAGAGGAAGTGCTGACGTGGGTGGTATTGATCGACCAAATGGTGAAGTCCAACATTGTCACTGTGGGGGACGTGAAAGAGATCAATAAGACAGTTTCCCGGATGAAAATCACAAAGGGTGATTTAGAACAACGGCAGAGGAGGGTGGGGAGGGTCCTGGAGGGTGGGAACCAGCTGATGACACAAGGGACTCTGTCAGAGGAGGAGGAGTTTGAGATCCAGGAACAGATGACCTTGCTGAATGCAAGGTGGGAGAGTACTCAGGATGGTGTGGAGCTGGGGCGGGAGCAGGTGGAGGACATGGTTGTGGACAGGCTGGAGTGGGACGACCACAGGGAAGAGACTGAAGAGCTCATGAGAAAATACGAGGCTCGCTTCTACATGCTGCAGCAGGCCCGGCGGGACCCACTTAGGAAACAAGTTTCTGATAATCAACTATTGCTTCAAGAGCTGGGGTCTGGCGATGGTGTCATCATGGGGTTTGATAATGTCCTGCAGAAACTTCTGGAAGAATACAGTGGCGATGACACAAGGAATGTGGAAGAAACCACGGAGTACTTGAAAACATCATGGGTCAATCTCAAACAAAGGATCGGTGATAGACAGAGTGCCTTGGAGGCTGAGCTACAGACAGTGCAGACTTCTCGTAGAGACCTGGAGAACTTTGTCAAGTGGCTTCAGGAAGGAGAAACCACAGGAAATGTGCTGGCCGATGCCTCTCAGCGGGAGAATGGTCTTCAGGACAGTGTCCTGGCCCGGCAGCTCCGACAGCAGATGCTGGACATCCAGGCAGAAATTGATGCCCACAATGACATATTTAAAAGCATCGATGGAAACCGGCAGAAGATGGTGAAAGCTCTGGGGAATTCTGAGGAAGCAACAATGCTTCAGCATCGACTGGATGACATGAACCAAAGATGGAATGATTTGAAGGCAAAATCTGCTAGCATCAGGGCCCATTTGGAGGCCAGTGCTGAGAAATGGAACCGGTTGCTGGCATCGCTGGAAGAGCTGATCAAATGGCTCAATATGAAAGATGAGGAGCTTAAGAAGCAGATGCCCATTGGAGGGGACGTCCCTGCCTTACAGCTCCAGTATGACCACTGCAAGGTGCTGAGACGTGAGCTAAAGGAGAAAGAGTATTCTGTGCTGAACGCCGTAGATCAAGCTCGAGTTTTTCTGGCTGATCAGCCAATAGAGGCCCCCGAAGAACCAAGAAGAAACCCACAATCAAAGACAGAGTTGACTCCTGAGGAGAGAGCCCAGAAGATCGCCAAAGCCATGCGCAAGCAGTCTTCTGAAGTCCGAGAGAAGTGGGAAAATCTAAATGCTGTCACTAGCAACTGGCAAAAGCAAGTAGGGAAGGCGTTAGAGAAACTCCGAGACCTGCAGGGAGCTATGGACGACCTGGACGCAGACATGAAGGAGGTGGAGGCTGTGCGGAATGGCTGGAAGCCCGTGGGAGACCTGCTTATAGACTCCCTGCAGGATCACATCGAGAAAACCCTGGCGTTTAGAGAAGAAATTGCACCAATCAACTTAAAAGTAAAAACAATGAATGACCTGTCCAGTCAGCTGTCTCCACTTGACTTGCATCCATCTCTAAAGATGTCTCGCCAGCTGGATGACCTTAATATGCGATGGAAACTTCTACAGGTTTCCGTGGACGATCGCCTTAAGCAGCTCCAGGAAGCCCACAGAGATTTTGGGCCATCTTCTCAACACTTTCTGTCCACTTCAGTCCAGCTGCCGTGGCAGAGATCCATTTCACATAATAAAGTGCCCTATTACATCAACCATCAAACACAGACAACCTGTTGGGATCATCCTAAAATGACTGAGCTCTTCCAATCCCTTGCTGATCTGAATAATGTACGTTTCTCTGCCTACCGCACAGCAATCAAAATTCGAAGGCTGCAAAAAGCATTATGTCTGGATCTCTTAGAGCTGAATACGACGAATGAAGTTTTCAAGCAGCACAAACTGAACCAAAATGATCAGCTCCTGAGTGTCCCAGACGTCATCAACTGTCTGACCACCACTTACGATGGGCTTGAGCAGCTGCACAAGGACTTGGTCAATGTTCCACTCTGCGTCGATATGTGTCTCAACTGGCTGCTCAACGTATACGACACGGGCCGGACTGGAAAAATTCGGGTACAGAGTCTGAAGATTGGATTGATGTCTCTCTCCAAAGGCCTCTTAGAAGAGAAATACAGATGTCTCTTTAAGGAGGTGGCAGGGCCAACAGAGATGTGTGACCAGCGGCAGCTTGGCCTGCTACTTCACGATGCCATCCAGATCCCTAGGCAGCTGGGGGAAGTAGCAGCCTTTGGGGGCAGTAACATTGAGCCCAGTGTCCGCAGCTGCTTCCAGCAGAATAACAACAAGCCAGAAATCAGTGTGAAGGAGTTTATAGACTGGATGCATTTGGAACCCCAGTCCATGGTGTGGTTGCCGGTTCTGCATCGGGTCGCAGCTGCTGAGACTGCAAAACATCAGGCCAAATGCAACATCTGCAAAGAATGCCCGATTGTTGGGTTCAGATACAGGAGCCTAAAGCATTTTAATTATGATGTCTGCCAGAGTTGCTTCTTTTCTGGAAGAACAGCAAAGGGCCACAAGTTACATTACCCGATGGTAGAATACTGCATACCGACAACATCTGGGGAAGATGTGAGAGATTTCACTAAGGTGCTGAAGAACAAGTTCAGGTCCAAGAAATATTTTGCCAAACATCCTCGGCTTGGCTACCTGCCTGTCCAGACCGTGCTGGAAGGGGACAACTTAGAAACTCAGGCAATGTGA

[0139] SEQ ID NO: 602 atgctttggtgggaggaagtggaggactgctacgagagagaggacgtgcagaagaaaaccttcaccaagtgggtgaacgc ccagttcagcaagttcggcaagcagcacatcgagaacctgttcagcgacctgcaggatggcaggagactgctggacctgc tggagggcctgaccggccagaagctgcccaaggagaagggcagcaccagagtgcacgccctgaacaacgtgaacaaggcc ctgagagtgctgcagaacaacaacgtggacctggtgaacatcggcagcaccgacatcgtggacggcaaccacaagctgac cctgggcctgatctggaacatcatcctgcactggcaggtgaagaacgtgatgaagaacatcatggccggcctgcagcaga ccaacagcgagaagatcctgctgagctgggtgaggcagagcaccagaaactacccccaggtgaacgtgatcaacttcacc acctcctggagcgacggcctggccctgaacgccctgatccacagccacagacccgacctgttcgactggaacagcgtggt gtgtcagcagagcgccacccagagactggagcacgccttcaacatcgccagataccagctgggcatcgagaagctgctgg accccgaggacgtggacaccacctaccccgacaagaaaagcatcctcatgtacattaccagcctgttccaggtgctgccc cagcaggtgtccatcgaggccatccaggaagtggaaatgctgcccaggccccccaaagtgaccaaggaggagcacttcca gctgcaccaccagatgcactacagccagcagatcacagtgagcctggcccagggctatgagagaaccagcagccccaagc ccagattcaagagctacgcctacacccaggccgcctacgtgaccacctccgaccccaccagaagccccttccccagccag cacctggaggcccccgaggacaagagcttcggcagcagcctgatggagagcgaagtgaacctggacagataccagaccgc cctggaggaagtgctgtcctggctgctgagcgccgaggacaccctgcaggcccagggcgagatcagcaacgacgtggaag tggtgaaggaccagttccacacccacgagggctacatgatggatctgaccgcccaccagggcagagtgggcaatatcctg cagctgggcagcaagctgatcggcaccggcaagctgagcgaggacgaggagaccgaagtgcaggagcagatgaacctgct gaacagcagatgggagtgcctgagagtggccagcatggagaagcagagcaacctgcacagagtgctgatggacctgcaga accagaagctgaaggagctgaacgactggctgaccaagaccgaggagcggaccagaaagatggaggaggagcccctgggc cccgacctggaggacctgaagagacaggtgcagcagcacaaagtgctgcaggaggacctggagcaggagcaggtgcgcgt gaacagcctgacccacatggtggtggtcgtggacgagagcagcggcgaccacgccacagccgccctggaagagcagctga aagtgctgggcgacagatgggccaatatttgtaggtggaccgaggacagatgggtgctgctgcaggaccagcccgacctg gcccctggcctgaccaccatcggcgccagccccacccagaccgtgaccctggtgacccagcccgtggtgacaaaggagac cgccatcagcaagctggagatgcccagctccctgatgctggaagtgcccacccaccgcctgctccagcagttccccctgg acctggagaagttcctggcctggctgaccgaggccgaaaccaccgccaatgtgctccaggacgccactagaaaggagagg ctgctggaggacagcaagggcgtgaaagagctgatgaagcagtggcaggatctgcagggcgaaatcgaggcccacaccga cgtgtaccacaacctggacgagaacagccagaagattctgaggagcctggagggcagcgacgacgccgtcctgctccaga ggaggctggacaacatgaacttcaagtggagcgagctgcggaagaagagcctgaacatccggagccacctggaagccagc agcgaccagtggaagagactgcacctgagcctgcaggagctgctggtgtggctgcagctgaaggacgacgagctgagcag acaggcccccatcggcggcgacttccccgccgtgcagaagcagaacgacgtgcaccgggccttcaagagggagctgaaaa ccaaggaacccgtgatcatgagcaccctggagacagtgcggatcttcctgaccgagcagcccctggagggactggagaag ctgtaccaggagcccagagagctgccccccgaggagagagcccagaacgtgaccaggctgctgagaaagcaggccgagga agtgaataccgagtgggagaagctgaatctgcacagcgccgactggcagagaaagatcgacgagaccctggagagactcc aggaactgcaggaagccaccgacgagctggacctgaagctgagacaggccgaagtgatcaagggcagctggcagcctgtgggcgatctgctgatcgactccctgcaggatcacctggagaaagtgaaggccctgcggggcgagatcgcccccctgaagga gaatgtgagccacgtgaacgacctggccagacagctgaccaccctgggcatccagctgagcccctacaacctgagcacac tggaggatctgaacacccggtggaaactgctgcaggtggccgtggaggatagagtgaggcagctgcacgaagcccacaga gacttcggccctgcctcccagcacttcctgagcaccagcgtgcagggcccctgggagagagccatctcccccaacaaagt gccctactacatcaaccacgagacccagaccacctgctgggaccaccctaagatgaccgagctgtatcagagcctggccg acctgaacaatgtgcggttcagcgcctacagaaccgccatgaagctgcggagactgcagaaggccctgtgcctggatctg ctgagcctgagcgccgcctgcgacgccctggaccagcacaacctgaagcagaatgaccagcccatggacatcctgcagat catcaactgcctgaccacaatctacgaccggctggaacaggagcacaacaacctggtgaatgtgcccctgtgcgtggaca tgtgcctgaattggctgctgaacgtgtacgacaccggcaggaccggcagaatccgcgtgctgagcttcaagaccggcatc atcagcctgtgcaaggcccacctggaggataagtaccgctacctgttcaagcaggtggccagcagcaccggcttctgcga tcagaggagactgggcctgctgctgcacgatagcatccagatccctaggcagctgggcgaagtggccagctttggcggca gcaacatcgagccctctgtgaggagctgcttccagttcgccaacaacaagcccgagatcgaggccgccctgttcctggac tggatgaggctggagcctcagagcatggtgtggctgcctgtgctgcacagagtggccgccgccgagaccgccaagcacca ggccaagtgcaatatctgcaaggagtgccccatcatcggcttccggtacaggagcctgaagcacttcaactacgacatct gccagagctgctttttcagcggcagagtggccaagggccacaaaatgcactaccccatggtggagtactgcacccccacc acctccggcgaggatgtgagagacttcgccaaagtgctgaagaataagttccggaccaagcggtactttgccaagcaccc caggatgggctacctgcccgtgcagaccgtgctggaaggcgacaacatgg

[0140] SEQ ID NO: 603ATGCTGTGGTGGGAGGAGGTGGAGGATTGTTATGAAAGGGAGGACGTGCAGAAGAAGA CTTTTACCAAGTGGGTGAACGCTCAGTTCAGCAAATTTGGGAAGCAGCACATCGAGAAT CTGTTTTCCGACCTGCAGGATGGGAGACGGCTGCTGGATCTGCTGGAAGGACTGACTGGC CAGAAGCTGCCCAAAGAGAAGGGGAGCACTAGGGTGCACGCCCTGAACAACGTGAACA AAGCTCTGAGAGTGCTGCAGAACAACAACGTGGATCTGGTGAATATTGGCAGTACTGATATCGTGGACGGGAACCACAAACTGACACTGGGCCTGATCTGGAACATTATTCTGCACTG GCAGGTGAAAAATGTGATGAAGAACATCATGGCCGGGCTGCAGCAGACCAATTCCGAGA AGATCCTGCTGTCTTGGGTGCGGCAGAGCACCCGCAACTATCCCCAGGTGAACGTGATTA ACTTCACTACATCCTGGAGCGACGGGCTGGCCCTGAATGCTCTGATTCACAGCCACAGGC CTGATCTGTTCGACTGGAATAGCGTGGTGTGCCAGCAGTCTGCCACACAGCGCCTGGAACATGCCTTCAATATCGCTCGGTACCAGCTGGGGATCGAAAAACTGCTGGACCCAGAGGAT GTGGACACTACATACCCAGATAAAAAGTCTATTCTGATGTACATTACTAGCCTGTTCCAG GTGCTGCCACAGCAGGTGTCTATTGAAGCCATTCAGGAGGTGGAAATGCTGCCCCGCCCC CCCAAAGTGACTAAAGAGGAGCATTTTCAGCTGCATCATCAGATGCATTACAGCCAGCA GATTACCGTGAGCCTGGCTCAGGGATATGAGCGCACCAGTAGTCCAAAACCACGGTTCAAGTCCTACGCTTATACCCAGGCTGCCTACGTGACAACTAGCGACCCTACTAGATCCCCCT TTCCATCCCAGCACCTGGAGGCCCCAGAGGACAAGAGCTTTGGGTCCAGCCTGATGGAA AGCGAGGTGAATCTGGATCGGTACCAGACAGCCCTGGAGGAGGTGCTGAGCTGGCTGCTGAGTGCTGAAGACACACTGCAGGCCCAGGGCGAAATTTCCAATGACGTGGAAGTGGTGAAGGATCAGTTCCACACACACGAGGGCTATATGATGGACCTGACAGCTCACCAGGGGCGCGTGGGCAATATCCTGCAGCTGGGCTCTAAACTGATCGGCACCGGGAAACTGAGTGAGGACGAGGAAACAGAAGTGCAGGAGCAGATGAACCTGCTGAACAGCCGCTGGGAGTGTCTGAGAGTGGCTAGTATGGAGAAGCAGTCCAACCTGCACCGGGTGCTGATGGACCTGCAGAACCAGAAACTGAAAGAGCTGAACGACTGGCTGACAAAGACTGAGGAACGCACAAGGAAGATGGAGGAGGAGCCACTGGGACCCGACCTGGAGGATCTGAAGAGACAGGTGCAGCAGCATAAGGTGCTGCAGGAGGATCTGGAACAGGAGCAGGTGCGGGTGAACTCCCTGACACATATGGTGGTGGTGGTGGACGAATCTAGTGGAGATCACGCCACCGCCGCCCTGGAGGAACAGCTGAAGGTGCTGGGGGACCGGTGGGCCAACATTTGCCGGTGGACCGAGGACAGGTGGGTGCTGCTGCAGGACATCCTGCTGAAATGGCAGAGGCTGACCGAGGAGCAGTGTCTGTTTAGTGCTTGGCTGAGCGAGAAAGAGGACGCCGTGAACAAGATCCACACAACCGGCTTTAAGGATCAGAACGAAATGCTGTCTAGCCTGCAGAAACTGGCTGTGCTGAAGGCCGATCTGGAGAAAAAGAAGCAGAGCATGGGCAAACTGTATAGCCTGAAACAGGACCTGCTGAGCACCCTGAAGAACAAGAGCGTGACCCAGAAGACAGAAGCCTGGCTGGATAACTTTGCCCGCTGCTGGGACAACCTGGTGCAGAAACTGGAGAAAAGTACAGCTCAGATCTCTCAGGCTGTGACCACAACCCAGCCTAGCCTGACCCAGACAACCGTGATGGAAACCGTGACCACCGTGACAACCCGCGAACAGATCCTGGTGAAACATGCCCAGGAAGAGCTGCCACCTCCACCTCCCCAGAAGAAGAGAACCCTGGAGCGGCTGCAGGAGCTGCAGGAAGCCACTGACGAACTGGACCTGAAGCTGAGGCAGGCCGAAGTGATTAAGGGGTCTTGGCAGCCTGTGGGCGATCTGCTGATTGATTCCCTGCAGGACCACCTGGAAAAGGTGAAGGCTCTGAGAGGCGAAATTGCTCCACTGAAGGAGAACGTGAGTCATGTGAACGATCTGGCTAGACAGCTGACAACACTGGGCATCCAGCTGAGCCCATACAATCTGAGCACACTGGAGGACCTGAATACCAGGTGGAAGCTGCTGCAGGTGGCTGTGGAAGACCGGGTGCGGCAGCTGCATGAGGCCCATCGCGACTTCGGACCAGCCAGCCAGCACTTTCTGAGCACATCCGTGCAGGGGCCCTGGGAGAGGGCCATTTCTCCCAACAAGGTGCCCTACTATATTAATCACGAGACCCAGACCACTTGTTGGGACCATCCCAAGATGACAGAACTGTACCAGTCCCTGGCCGATCTGAACAACGTGAGGTTTAGCGCTTACAGAACCGCTATGAAGCTGAGACGGCTGCAGAAGGCCCTGTGCCTGGATCTGCTGTCCCTGTCCGCCGCCTGCGATGCCCTGGATCAGCATAATCTGAAGCAGAACGATCAGCCAATGGATATCCTGCAGATCATCAACTGCCTGACCACTATCTACGACAGGCTGGAGCAGGAGCACAACAACCTGGTGAACGTGCCTCTGTGCGTGGATATGTGCCTGAACTGGCTGCTGAACGTGTATGACACTGGGCGCACCGGCCGGATCAGAGTGCTGAGTTTTAAAACTGGGATTATCTCCCTGTGTAAGGCCCACCTGGAGGACAAGTACAGGTACCTGTTCAAGCAGGTGGCTAGTAGCACTGGATTTTGTGACCAGCGCCGCCTGGGACTGCTGCTGCATGATAGTATCCAGATTCCTAGACAGCTGGGAGAGGTGGCTAGTTTCGGAGGATCTAACATCGAACCCAGCGTGCGCAGCTGTTTCCAGTTTGCCAATAACAAACCTGAAATCGAGGCTGCTCTGTTCCTGGATTGGATGCGCCTGGAACCACAGAGCATGGTGTGGCTGCCTGTGCTGCACAGAGTGGCTGC CGCCGAAACTGCCAAGCACCAGGCTAAATGCAACATCTGCAAGGAATGTCCCATTATCG GCTTTCGCTACAGGAGTCTGAAACATTTTAACTACGATATTTGCCAGAGCTGCTTCTTTTC CGGAAGAGTGGCCAAAGGACACAAGATGCACTACCCTATGGTGGAATATTGCACCCCAA CTACATCTGGCGAAGATGTGCGCGATTTTGCCAAGGTGCTGAAGAATAAGTTTCGGACTA AGAGGTACTTCGCCAAGCACCCCCGCATGGGGTATCTGCCAGTGCAGACAGTGCTGGAA GGAGACAATATGGAGACCGATACAATGTGA

[0141] In some embodiments of any of the aspects, the polypeptide does not comprise the sequence of any of SEQ ID NO: 604-607.

[0142] In some embodiments of any of the aspects, the polypeptide does not comprise the sequence of SEQ ID NO: 604. In some embodiments of any of the aspects, the polypeptide does not comprise the sequence of SEQ ID NO: 605. In some embodiments of any of tire aspects, the polypeptide does not comprise the sequence of SEQ ID NO: 606. In some embodiments of any of the aspects, the polypeptide does not comprise the sequence of SEQ ID NO: 607.

[0143] SEQ ID NO: 604MLWWEEVEDCYEREDVQKKTFTKWVNAQFSKFGKQHIENLFSDLQDGRRLLDLLEGLTGQ KLPKEKGSTRVHALNNVNKALRVLQNNNVDLVNIGSTDIVDGNHKLTLGLIWNIILHWQV KNVMKNIMAGLQQTNSEKILLSWVRQSTRNYPQVNVINFTTSWSDGLALNALIHSHRPDL FDWNSVVCQQSATQRLEHAFNIARYQLGIEKLLDPEDVDTTYPDKKSILMYITSLFQVLP QQVSIEAIQEVEMLPRPPKVTKEEHFQLHHQMHYSQQITVSLAQGYERTSSPKPRFKSYA YTQAAYVTTSDPTRSPFPSQHLEAPEDKSFGSSLMESEVNLDRYQTALEEVLSWLLSAED TLQAQGEISNDVEVVKDQFHTHEGYMMDLTAHQGRVGNILQLGSKLIGTGKLSEDEETEV QEQMNLLNSRWECLRVASMEKQSNLHRVLMDLQNQKLKELNDWLTKTEERTRKMEEEPLG PDLEDLKRQVQQHKVLQEDLEQEQVRVNSLTHMVVVVDESSGDHATAALEEQLKVLGDRW ANICRWTEDRWVLLQDQPDLAPGLTTIGASPTQTVTLVTQPVVTKETAISKLEMPSSLMLEVPTHRLLQQFPLDLEKFLAWLTEAETTANVLQDATRKERLLEDSKGVKELMKQWQDLQG EIEAHTDVYHNLDENSQKILRSLEGSDDAVLLQRRLDNMNFKWSELRKKSLNIRSHLEAS SDQWKRLHLSLQELLVWLQLKDDELSRQAPIGGDFPAVQKQNDVHRAFKRELKTKEPVIM STLETVRIFLTEQPLEGLEKLYQEPRELPPEERAQNVTRLLRKQAEEVNTEWEKLNLHSA DWQRKIDETLERLQELQEATDELDLKLRQAEVIKGSWQPVGDLLIDSLQDHLEKVKALRG EIAPLKENVSHVNDLARQLTTLGIQLSPYNLSTLEDLNTRWKLLQVAVEDRVRQLHEAHR DFGPASQHFLSTSVQGPWERAISPNKVPYYINHETQTTCWDHPKMTELYQSLADLNNVRF SAYRTAMKLRRLQKALCLDLLSLSAACDALDQHNLKQNDQPMDILQIINCLTTIYDRLEQ EHNNLVNVPLCVDMCLNWLLNVYDTGRTGRIRVLSFKTGIISLCKAHLEDKYRYLFKQVA SSTGFCDQRRLGLLLHDSIQIPRQLGEVASFGGSNIEPSVRSCFQFANNKPEIEAALFLD WMRLEPQSMVWLPVLHRVAAAETAKHQAKCNICKECPIIGFRYRSLKHFNYDICQSCFFSGRVAKGHKMHYPMVEYCTPTTSGEDVRDFAKVLKNKFRTKRYFAKHPRMGYLPVQTVLEG DNMET

[0144] SEQ ID NO: 605MAKYGDLEARPDDGQNEFSDIIKSRSDEHNDVQKKTFTKWINARFSKSGKPPISDMFSDL KDGRKLLDLLEGLTGTSLPKERGSTRVHALNNVNRVLQVLHQNNVDLVNIGGTDIVDGNP KLTLGLLWSIILHWQVKDVMKDIMSDLQQTNSEKILLSWVRQTTRPYSQVNVLNFTTSWT DGLAFNAVLHRHKPDLFSWDRVVKMSPIERLEHAFSKAHTYLGIEKLLDPEDVAVHLPDKKSIIMYLTSLFEVLPQQVTIDAIREVETLPRKYKKECEEEEIHIQSAVLAEEGQSPRAET PSTVTEVDMDLDSYQIALEEVLTWLVLIDQMLKSNIVTVGDVKEINKTVSRMKITKADLE QRQSSVGSVLQAGNQLMTQGTLSEEEEFEIQEQMTLLNARWESTQHGVELRRQQLEDMVV DSLQWDDHREETEELMRKYEARFYMLQQARRDPLSKQVSDNQLLLQELGSGDGVIMAFDN VLQKLLEEYSGDDTRNVEETTEYLKTSWVNLKQSIADRQSALEAELQTVQTSRRDLENFV KWLQEAETTANVLADASQRENALQDSVLARQLRQQMLDIQAEIDAHNDIFKSIDGNRQKM VKALGNSEEATMLQHRLDDMNQRWNDLKAKSASIRAHLEASAEKWNRLLASLEELIKWLN MKDEELKKQMPIGGDVPALQLQYDHCKVLRRELKEKEYSVLNAVDQARVFLADQPIEAPE EPRRNPQSKTELTPEERAQKIAKAMRKQSSEVREKWENLNAVTSNWQKQVGKALEKLRDL QGAMDDLDADMKEVEAVRNGWKPVGDLLIDSLQDHIEKTLAFREEIAPINLKVKTMNDLS SQLSPLDLHPSLKMSRQLDDLNMRWKLLQVSVDDRLKQLQEAHRDFGPSSQHFLSTSVQL PWQRSISHNKVPYYINHQTQTTCWDHPKMTELFQSLADLNNVRFSAYRTAIKIRRLQKAL CLDLLELNTTNEVFKQHKLNQNDQLLSVPDVINCLTTTYDGLEQLHKDLVNVPLCVDMCL NWLLNVYDTGRTGKIRVQSLKIGLMSLSKGLLEEKYRCLFKEVAGPTEMCDQRQLGLLLH DAIQIPRQLGEVAAFGGSNIEPSVRSCFQQNNNKPEISVKEFIDWMHLEPQSMVWLPVLH RVAAAETAKHQAKCNICKECPIVGFRYRSLKHFNYDVCQSCFFSGRTAKGHKLHYPMVEY CIPTTSGEDVRDFTKVLKNKFRSKKYFAKHPRLGYLPVQTVLEGDNLETQAM

[0145] SEQ ID NO: 606MLWWEEVEDCYEREDVQKKTFTKWVNAQFSKFGKQHIENLFSDLQDGRRLLDLLEGLTGQKLPKEKGSTRVHALNNVNKALRVLQNNNVDLVNIGSTDIVDGNHKLTLGLIWNIILHWQV KNVMKNIMAGLQQTNSEKILLSWVRQSTRNYPQVNVINFTTSWSDGLALNALIHSHRPDL FDWNSVVCQQSATQRLEHAFNIARYQLGIEKLLDPEDVDTTYPDKKSILMYITSLFQVLP QQVSIEAIQEVEMLPRPPKVTKEEHFQLHHQMHYSQQITVSLAQGYERTSSPKPRFKSYA YTQAAYVTTSDPTRSPFPSQHLEAPEDKSFGSSLMESEVNLDRYQTALEEVLSWLLSAED TLQAQGEISNDVEVVKDQFHTHEGYMMDLTAHQGRVGNILQLGSKLIGTGKLSEDEETEV QEQMNLLNSRWECLRVASMEKQSNLHRVLMDLQNQKLKELNDWLTKTEERTRKMEEEPLG PDLEDLKRQVQQHKVLQEDLEQEQVRVNSLTHMVVVVDESSGDHATAALEEQLKVLGDRW ANICRWTEDRWVLLQDQPDLAPGLTTIGASPTQTVTLVTQPVVTKETAISKLEMPSSLML EVPTHRLLQQFPLDLEKFLAWLTEAETTANVLQDATRKERLLEDSKGVKELMKQWQDLQGEIEAHTDVYHNLDENSQKILRSLEGSDDAVLLQRRLDNMNFKWSELRKKSLNIRSHLEAS SDQWKRLHLSLQELLVWLQLKDDELSRQAPIGGDFPAVQKQNDVHRAFKRELKTKEPVIM STLETVRIFLTEQPLEGLEKLYQEPRELPPEERAQNVTRLLRKQAEEVNTEWEKLNLHSA DWQRKIDETLERLQELQEATDELDLKLRQAEVIKGSWQPVGDLLIDSLQDHLEKVKALRG EIAPLKENVSHVNDLARQLTTLGIQLSPYNLSTLEDLNTRWKLLQVAVEDRVRQLHEAHR DFGPASQHFLSTSVQGPWERAISPNKVPYYINHETQTTCWDHPKMTELYQSLADLNNVRF SAYRTAMKLRRLQKALCLDLLSLSAACDALDQHNLKQNDQPMDILQIINCLTTIYDRLEQ EHNNLVNVPLCVDMCLNWLLNVYDTGRTGRIRVLSFKTGIISLCKAHLEDKYRYLFKQVA SSTGFCDQRRLGLLLHDSIQIPRQLGEVASFGGSNIEPSVRSCFQFANNKPEIEAALFLD WMRLEPQSMVWLPVLHRVAAAETAKHQAKCNICKECPIIGFRYRSLKHFNYDICQSCFFS GRVAKGHKMHYPMVEYCTPTTSGEDVRDFAKVLKNKFRTKRYFAKHPRMGYLPVQTVLEG DNM

[0146] SEQ ID NO: 607MLWWEEVEDCYEREDVQKKTFTKWVNAQFSKFGKQHIENLFSDLQDGRRLLDLLEGLTGQKLPKEKGSTRVHALNNVNKALRVLQNNNVDLVNIGSTDIVDGNHKLTLGLIWNIILHWQVKNVMKNIMAGLQQTNSEKILLSWVRQSTRNYPQVNVINFTTSWSDGLALNALIHSHRPDLFDWNSVVCQQSATQRLEHAFNIARYQLGIEKLLDPEDVDTTYPDKKSILMYITSLFQVLP QQVSIEAIQEVEMLPRPPKVTKEEHFQLHHQMHYSQQITVSLAQGYERTSSPKPRFKSYA YTQAAYVTTSDPTRSPFPSQHLEAPEDKSFGSSLMESEVNLDRYQTALEEVLSWLLSAED TLQAQGEISNDVEVVKDQFHTHEGYMMDLTAHQGRVGNILQLGSKLIGTGKLSEDEETEV QEQMNLLNSRWECLRVASMEKQSNLHRVLMDLQNQKLKELNDWLTKTEERTRKMEEEPLG PDLEDLKRQVQQHKVLQEDLEQEQVRVNSLTHMVVVVDESSGDHATAALEEQLKVLGDRW ANICRWTEDRWVLLQDILLKWQRLTEEQCLFSAWLSEKEDAVNKIHTTGFKDQNEMLSSL QKLAVLKADLEKKKQSMGKLYSLKQDLLSTLKNKSVTQKTEAWLDNFARCWDNLVQKLE KSTAQISQAVTTTQPSLTQTTVMETVTTVTTREQILVKHAQEELPPPPPQKKRTLERLQELQEATDELDLKLRQAEVIKGSWQPVGDLLIDSLQDHLEKVKALRGEIAPLKENVSHVNDLARQLTTLGIQLSPYNLSTLEDLNTRWKLLQVAVEDRVRQLHEAHRDFGPASQHFLSTSVQG PWERAISPNKVPYYINHETQTTCWDHPKMTELYQSLADLNNVRFSAYRTAMKLRRLQKAL CLDLLSLSAACDALDQHNLKQNDQPMDILQIINCLTTIYDRLEQEHNNLVNVPLCVDMCLNWLLNVYDTGRTGRIRVLSFKTGIISLCKAHLEDKYRYLFKQVASSTGFCDQRRLGLLLHDSIQIPRQLGEVASFGGSNIEPSVRSCFQFANNKPEIEAALFLDWMRLEPQSMVWLPVLHRVAAAETAKHQAKCNICKECPIIGFRYRSLKHFNYDICQSCFFSGRVAKGHKMHYPMVEY CTPTTSGEDVRDFAKVLKNKFRTKRYFAKHPRMGYLPVQTVLEGDNMETDTM

[0147] In one aspect of any of the embodiments, described herein is a polypeptide comprising a utrophin N-terminal portion and a dystrophin C-terminal portion. In one aspect of any of theembodiments, described herein is a polypeptide comprising a dystrophin N-tcrminal portion and a utrophin C-terminal portion.

[0148] In one aspect of any of the the embodiments, described herein is a microutrophin polypeptide comprising a utrophin NT domain, a utrophin SLR domain 1, a utrophin SLR domain 2, and a utrophin SLR domain 3, wherein the microutrophin polypeptide is encoded by a codon optimized nucleic acid sequence. In one aspect of any of the the embodiments, described herein is a microutrophin polypeptide consisting of a utrophin NT domain, a utrophin SLR domain 1, a utrophin SLR domain 2, and a utrophin SLR domain 3. wherein the microutrophin polypeptide is encoded by a codon optimized nucleic acid sequence.

[0149] In one aspect of any of the the embodiments, described herein is a microutrophin polypeptide comprising a utrophin NT domain, a utrophin SLR domain 1, a utrophin SLR domain 2, and a utrophin SLR domain 3, wherein each of the utrophin NT domain, utrophin SLR domain 1, utrophin SLR domain 2, and utrophin SLR domain 3 are encoded by a codon optimized nucleic acid sequence. In one aspect of any of the the embodiments, described herein is a microutrophin polypeptide consisting of a utrophin NT domain, a utrophin SLR domain 1, a utrophin SLR domain 2. and a utrophin SLR domain 3, wherein each of the utrophin NT domain, utrophin SLR domain 1. utrophin SLR domain 2, and utrophin SLR domain 3 are encoded by a codon optimized nucleic acid sequence.

[0150] In some embodiments of any of the aspects, the microutrophin polypeptide further comprises a utrophin hinge domain 1, utrophin hinge domain 2. and utrophin hinge domain 4. In some embodiments of any of the aspects, the microutrophin polypeptide further comprises a utrophin hinge domain 1. In some embodiments of any of the aspects, the microutrophin polypeptide further comprises a utrophin hinge domain 2. In some embodiments of any of the aspects, the microutrophin polypeptide further comprises a utrophin hinge domain 4.

[0151] In some embodiments of any of the aspects, the microutrophin poly peptide further comprises a utrophin SLR22 domain and a utrophin CR domain. In some embodiments of any of the aspects, the microutrophin polypeptide further comprises a utrophin SLR22 domain. In some embodiments of any of the aspects, the microutrophin polypeptide further comprises a utrophin CR domain.

[0152] In some embodiments of any of the aspects, the microutrophin polypeptide further comprises a utrophin hinge domain 1. utrophin hinge domain 2, utrophin hinge domain 4, a utrophin SLR22 domain, and a utrophin CR domain.

[0153] In some embodiments of any of the aspects, one or more of utrophin hinge domain 1, the utrophin hinge domain 2, the utrophin hinge domain 4, the utrophin SLR22 domain, and the utrophin CR domain are encoded by a codon optimized nucleic acid sequence. In some embodiments of any of the aspects, each of utrophin hinge domain 1, the utrophin hinge domain 2, the utrophin hinge domain4, the utrophin SLR22 domain, and the utrophin CR domain arc encoded by a codon optimized nucleic acid sequence.

[0154] In some embodiments of any of the aspects, the microutrophin polypeptide is encoded by a codon-optimized sequence selected from one of SEQ ID NOs: 100-111 or 400-474. In some embodiments of any of the aspects, the microutrophin polypeptide is encoded by a codon-optimized sequence selected from one of SEQ ID NOs: 100-111, 400-432, and 434-474.

[0155] Described herein are codon-optimised versions of chimeric utrophin polypeptides.

[0156] In one aspect of any of the embodiments, described herein is a nucleic acid molecule comprising a sequence with at least 70% sequence identity to one of SEQ ID NOs: 100-111. In one aspect of any of the embodiments, described herein is a nucleic acid molecule comprising a sequence with at least 75% sequence identity to one of SEQ ID NOs: 100-111. In one aspect of any of the embodiments, described herein is a nucleic acid molecule comprising a sequence with at least 80% sequence identity to one of SEQ ID NOs : 100- 111. In one aspect of any of the embodiments, described herein is a nucleic acid molecule comprising a sequence with at least 85% sequence identity to one of SEQ ID NOs: 100-111. In one aspect of any of the embodiments, described herein is a nucleic acid molecule comprising a sequence with at least 90% sequence identity to one of SEQ ID NOs: 100-111. In one aspect of any of the embodiments, described herein is a nucleic acid molecule comprising a sequence with at least 95% sequence identity to one of SEQ ID NOs: 100- 111. In one aspect of any of the embodiments, described herein is a nucleic acid molecule comprising a sequence with at least 98% sequence identity to one of SEQ ID NOs: 100-111. In one aspect of any of the embodiments, described herein is a nucleic acid molecule comprising a sequence with at least 99% sequence identity to one of SEQ ID NOs : 100- 111. In one aspect of any of the embodiments, described herein is a nucleic acid molecule comprising a sequence identical to one of SEQ ID NOs: 100-111.

[0157] In one aspect of any of the embodiments, described herein is a nucleic acid molecule comprising a sequence with at least 70% sequence identity to one of SEQ ID NOs: 100-111 or a functional equivalent thereof, e.g., encoding a chimeric trophin polypeptide. In one aspect of any of the embodiments, described herein is a nucleic acid molecule comprising a sequence with at least 75% sequence identity to one of SEQ ID NOs: 100-111 or a functional equivalent thereof, e.g., encoding a chimeric trophin polypeptide. In one aspect of any of the embodiments, described herein is a nucleic acid molecule comprising a sequence with at least 80% sequence identity to one of SEQ ID NOs: 100-111 or a functional equivalent thereof, e.g., encoding a chimeric trophin polypeptide. In one aspect of any of the embodiments, described herein is a nucleic acid molecule comprising a sequence with at least 85% sequence identity to one of SEQ ID NOs: 100-111 or a functional equivalent thereof, e.g., encoding a chimeric trophin polypeptide. In one aspect of any of the embodiments, described herein is a nucleic acid molecule comprising a sequence with at least 90% sequence identityto one of SEQ ID NOs: 100-111 or a functional equivalent thereof, e.g., encoding a chimeric trophin polypeptide. In one aspect of any of the embodiments, described herein is a nucleic acid molecule comprising a sequence with at least 95% sequence identity to one of SEQ ID NOs: 100-111 or a functional equivalent thereof, e.g., encoding a chimeric trophin polypeptide. In one aspect of any of the embodiments, described herein is a nucleic acid molecule comprising a sequence with at least 98% sequence identity to one of SEQ ID NOs: 100-111 or a functional equivalent thereof, e.g., encoding a chimeric trophin polypeptide. In one aspect of any of the embodiments, described herein is a nucleic acid molecule comprising a sequence with at least 99% sequence identity to one of SEQ ID NOs: 100-111 or a functional equivalent thereof, e.g., encoding a chimeric trophin polypeptide. In one aspect of any of the embodiments, described herein is a nucleic acid molecule comprising a sequence identical to one of SEQ ID NOs: 100-111 or a functional equivalent thereof, e.g., encoding a chimeric trophin polypeptide.

[0158] In one aspect of any of the embodiments, described herein is a nucleic acid molecule consisting of a sequence with at least 80% sequence identity to one of SEQ ID NOs: 100-111. In one aspect of any of the embodiments, described herein is a nucleic acid molecule consisting of a sequence with at least 85% sequence identity to one of SEQ ID NOs: 100-111. In one aspect of any of the embodiments, described herein is a nucleic acid molecule consisting of a sequence with at least 90% sequence identity to one of SEQ ID NOs: 100-111. In one aspect of any of the embodiments, described herein is a nucleic acid molecule consisting of a sequence with at least 95% sequence identity to one of SEQ ID NOs: 100-111. In one aspect of any of the embodiments, described herein is a nucleic acid molecule consisting of a sequence with at least 98% sequence identity to one of SEQ ID NOs: 100-111. In one aspect of any of the embodiments, described herein is a nucleic acid molecule consisting of a sequence with at least 99% sequence identity to one of SEQ ID NOs: 100- 111. In one aspect of any of the embodiments, described herein is a nucleic acid molecule consisting of a sequence identical to one of SEQ ID NOs: 100-111.

[0159] In one aspect of any of the embodiments, described herein is a nucleic acid molecule comprising a sequence with at least 70% sequence identity to one of SEQ ID NOs: 100-109. In one aspect of any of the embodiments, described herein is a nucleic acid molecule comprising a sequence with at least 75% sequence identity to one of SEQ ID NOs: 100-109. In one aspect of any of the embodiments, described herein is a nucleic acid molecule comprising a sequence with at least 80% sequence identity to one of SEQ ID NOs: 100-109. In one aspect of any of the embodiments, described herein is a nucleic acid molecule comprising a sequence with at least 85% sequence identity to one of SEQ ID NOs: 100-109. In one aspect of any of the embodiments, described herein is a nucleic acid molecule comprising a sequence with at least 90% sequence identity to one of SEQ ID NOs: 100-109. In one aspect of any of the embodiments, described herein is a nucleic acid molecule comprising a sequence with at least 95% sequence identity to one of SEQ ID NOs: 100-109. In oneaspect of any of the embodiments, described herein is a nucleic acid molecule comprising a sequence with at least 98% sequence identity to one of SEQ ID NOs: 100-109. In one aspect of any of the embodiments, described herein is a nucleic acid molecule comprising a sequence with at least 99% sequence identity to one of SEQ ID NOs: 100-109. In one aspect of any of the embodiments, described herein is a nucleic acid molecule comprising a sequence identical to one of SEQ ID NOs: 100-109.

[0160] In one aspect of any of the embodiments, described herein is a nucleic acid molecule comprising a sequence with at least 70% sequence identity to one of SEQ ID NOs: 100-109 or a functional equivalent thereof, e.g., encoding a chimeric trophin polypeptide. In one aspect of any of the embodiments, described herein is a nucleic acid molecule comprising a sequence with at least 75% sequence identity to one of SEQ ID NOs: 100-109 or a functional equivalent thereof, e.g., encoding a chimeric trophin polypeptide. In one aspect of any of the embodiments, described herein is a nucleic acid molecule comprising a sequence with at least 80% sequence identity to one of SEQ ID NOs: 100-109 or a functional equivalent thereof, e.g., encoding a chimeric trophin polypeptide. In one aspect of any of the embodiments, described herein is a nucleic acid molecule comprising a sequence with at least 85% sequence identity to one of SEQ ID NOs: 100-109 or a functional equivalent thereof, e.g., encoding a chimeric trophin polypeptide. In one aspect of any of the embodiments, described herein is a nucleic acid molecule comprising a sequence with at least 90% sequence identity to one of SEQ ID NOs: 100-109 or a functional equivalent thereof, e.g.. encoding a chimeric trophin polypeptide. In one aspect of any of the embodiments, described herein is a nucleic acid molecule comprising a sequence with at least 95% sequence identity to one of SEQ ID NOs: 100-109 or a functional equivalent thereof, e.g., encoding a chimeric trophin polypeptide. In one aspect of any of the embodiments, described herein is a nucleic acid molecule comprising a sequence with at least 98% sequence identity to one of SEQ ID NOs: 100-109 or a functional equivalent thereof, e.g.. encoding a chimeric trophin poly peptide. In one aspect of any of the embodiments, described herein is a nucleic acid molecule comprising a sequence with at least 99% sequence identity to one of SEQ ID NOs: 100-109 or a functional equivalent thereof, e.g., encoding a chimeric trophin polypeptide. In one aspect of any of the embodiments, described herein is a nucleic acid molecule comprising a sequence identical to one of SEQ ID NOs: 100-109 or a functional equivalent thereof, e.g., encoding a chimeric trophin polypeptide.

[0161] In one aspect of any of the embodiments, described herein is a nucleic acid molecule consisting of a sequence with at least 80% sequence identity to one of SEQ ID NOs: 100-109. In one aspect of any of the embodiments, described herein is a nucleic acid molecule consisting of a sequence with at least 85% sequence identity to one of SEQ ID NOs: 100-109. In one aspect of any of the embodiments, described herein is a nucleic acid molecule consisting of a sequence with at least 90% sequence identity to one of SEQ ID NOs: 100-109. In one aspect of any of the embodiments,described herein is a nucleic acid molecule consisting of a sequence with at least 95% sequence identity to one of SEQ ID NOs: 100-109. In one aspect of any of the embodiments, described herein is a nucleic acid molecule consisting of a sequence with at least 98% sequence identity to one of SEQ ID NOs: 100-109. In one aspect of any of the embodiments, described herein is a nucleic acid molecule consisting of a sequence with at least 99% sequence identity to one of SEQ ID NOs: 100- 109. In one aspect of any of the embodiments, described herein is a nucleic acid molecule consisting of a sequence identical to one of SEQ ID NOs: 100-109.

[0162] In one aspect of any of the embodiments, described herein is a nucleic acid molecule comprising a sequence with at least 80% sequence identity to one of SEQ ID NOs: 100-103. In one aspect of any of the embodiments, described herein is a nucleic acid molecule comprising a sequence with at least 85% sequence identity to one of SEQ ID NOs: 100-103. In one aspect of any of the embodiments, described herein is a nucleic acid molecule comprising a sequence with at least 90% sequence identity to one of SEQ ID NOs: 100-103. In one aspect of any of the embodiments, described herein is a nucleic acid molecule comprising a sequence with at least 95% sequence identity to one of SEQ ID NOs: 100-103. In one aspect of any of the embodiments, described herein is a nucleic acid molecule comprising a sequence with at least 98% sequence identity to one of SEQ ID NOs: 100-103. In one aspect of any of the embodiments, described herein is a nucleic acid molecule comprising a sequence with at least 99% sequence identity to one of SEQ ID NOs: 100-103. In one aspect of any of the embodiments, described herein is a nucleic acid molecule comprising a sequence identical to one of SEQ ID NOs: 100-103.

[0163] In one aspect of any of the embodiments, described herein is a nucleic acid molecule consisting of a sequence with at least 80% sequence identity to one of SEQ ID NOs: 100-103. In one aspect of any of the embodiments, described herein is a nucleic acid molecule consisting of a sequence with at least 85% sequence identity to one of SEQ ID NOs: 100-103. In one aspect of any of the embodiments, described herein is a nucleic acid molecule consisting of a sequence with at least 90% sequence identity to one of SEQ ID NOs: 100-103. In one aspect of any of the embodiments, described herein is a nucleic acid molecule consisting of a sequence with at least 95% sequence identity to one of SEQ ID NOs: 100-103. In one aspect of any of the embodiments, described herein is a nucleic acid molecule consisting of a sequence with at least 98% sequence identity to one of SEQ ID NOs: 100-103. In one aspect of any of the embodiments, described herein is a nucleic acid molecule consisting of a sequence with at least 99% sequence identity to one of SEQ ID NOs: 100- 103. In one aspect of any of the embodiments, described herein is a nucleic acid molecule consisting of a sequence identical to one of SEQ ID NOs: 100-103.

[0164] In one aspect of any of the embodiments, described herein is a nucleic acid molecule comprising a sequence with at least 80% sequence identity to one of SEQ ID NOs: 101-103. In one aspect of any of the embodiments, described herein is a nucleic acid molecule comprising a sequencewith at least 85% sequence identity to one of SEQ ID NOs: 101-103. In one aspect of any of the embodiments, described herein is a nucleic acid molecule comprising a sequence with at least 90% sequence identity to one of SEQ ID NOs: 101-103. In one aspect of any of tire embodiments, described herein is a nucleic acid molecule comprising a sequence with at least 95% sequence identity to one of SEQ ID NOs: 101-103. In one aspect of any of the embodiments, described herein is a nucleic acid molecule comprising a sequence with at least 98% sequence identity to one of SEQ ID NOs: 101-103. In one aspect of any of the embodiments, described herein is a nucleic acid molecule comprising a sequence with at least 99% sequence identity to one of SEQ ID NOs: 101-103. In one aspect of any of the embodiments, described herein is a nucleic acid molecule comprising a sequence identical to one of SEQ ID NOs: 101-103.

[0165] In one aspect of any of the embodiments, described herein is a nucleic acid molecule consisting of a sequence with at least 80% sequence identity to one of SEQ ID NOs: 101-103. In one aspect of any of the embodiments, described herein is a nucleic acid molecule consisting of a sequence with at least 85% sequence identity to one of SEQ ID NOs: 101-103. In one aspect of any of the embodiments, described herein is a nucleic acid molecule consisting of a sequence with at least 90% sequence identity to one of SEQ ID NOs: 101-103. In one aspect of any of the embodiments, described herein is a nucleic acid molecule consisting of a sequence with at least 95% sequence identity to one of SEQ ID NOs: 101-103. In one aspect of any of the embodiments, described herein is a nucleic acid molecule consisting of a sequence with at least 98% sequence identity to one of SEQ ID NOs: 101-103. In one aspect of any of the embodiments, described herein is a nucleic acid molecule consisting of a sequence with at least 99% sequence identity to one of SEQ ID NOs: 101- 103. In one aspect of any of the embodiments, described herein is a nucleic acid molecule consisting of a sequence identical to one of SEQ ID NOs: 101-103.

[0166] In one aspect of any of the embodiments, described herein is a nucleic acid molecule comprising a sequence with at least 80% sequence identity to one of SEQ ID NOs: 100, 102, or 103. In one aspect of any of the embodiments, described herein is a nucleic acid molecule comprising a sequence with at least 85% sequence identity to one of SEQ ID NOs: 100, 102, or 103. In one aspect of any of the embodiments, described herein is a nucleic acid molecule comprising a sequence with at least 90% sequence identity to one of SEQ ID NOs: 100. 102, or 103. In one aspect of any of the embodiments, described herein is a nucleic acid molecule comprising a sequence with at least 95% sequence identity to one of SEQ ID NOs: 100, 102, or 103. In one aspect of any of the embodiments, described herein is a nucleic acid molecule comprising a sequence with at least 98% sequence identity to one of SEQ ID NOs: 100, 102. or 103. In one aspect of any of the embodiments, described herein is a nucleic acid molecule comprising a sequence with at least 99% sequence identity to one of SEQ ID NOs: 100. 102, or 103. In one aspect of any of the embodiments, described herein is a nucleic acid molecule comprising a sequence identical to one of SEQ ID NOs: 100, 102. or 103.

[0167] In one aspect of any of the embodiments, described herein is a nucleic acid molecule consisting of a sequence with at least 80% sequence identity to one of SEQ ID NOs: 100, 102, or 103. In one aspect of any of the embodiments, described herein is a nucleic acid molecule consisting of a sequence with at least 85% sequence identity to one of SEQ ID NOs: 100, 102, or 103. In one aspect of any of the embodiments, described herein is a nucleic acid molecule consisting of a sequence with at least 90% sequence identity to one of SEQ ID NOs: 100, 102, or 103. In one aspect of any of the embodiments, described herein is a nucleic acid molecule consisting of a sequence with at least 95% sequence identity to one of SEQ ID NOs: 100, 102, or 103. In one aspect of any of the embodiments, described herein is a nucleic acid molecule consisting of a sequence with at least 98% sequence identity to one of SEQ ID NOs: 100, 102. or 103. In one aspect of any of the embodiments, described herein is a nucleic acid molecule consisting of a sequence with at least 99% sequence identity to one of SEQ ID NOs: 100, 102. or 103. In one aspect of any of the embodiments, described herein is a nucleic acid molecule consisting of a sequence identical to one of SEQ ID NOs: 100, 102. or 103.

[0168] In one aspect of any of the embodiments, described herein is a nucleic acid molecule comprising a sequence with at least 80% sequence identity to SEQ ID NO: 100. In one aspect of any of the embodiments, described herein is a nucleic acid molecule comprising a sequence with at least 85% sequence identity to SEQ ID NO: 100. In one aspect of any of the embodiments, described herein is a nucleic acid molecule comprising a sequence with at least 90% sequence identity to SEQ ID NO: 100. In one aspect of any of the embodiments, described herein is a nucleic acid molecule comprising a sequence with at least 95% sequence identity to SEQ ID NO: 100. In one aspect of any of the embodiments, described herein is a nucleic acid molecule comprising a sequence with at least 98% sequence identity to SEQ ID NO: 100. In one aspect of any of the embodiments, described herein is a nucleic acid molecule comprising a sequence with at least 99% sequence identity to SEQ ID NO: 100. In one aspect of any of the embodiments, described herein is a nucleic acid molecule comprising a sequence identical to SEQ ID NO: 100.

[0169] In one aspect of any of the embodiments, described herein is a nucleic acid molecule consisting of a sequence with at least 80% sequence identity to SEQ ID NO: 100. In one aspect of any of the embodiments, described herein is a nucleic acid molecule consisting of a sequence with at least 85% sequence identity to SEQ ID NO: 100. In one aspect of any of the embodiments, described herein is a nucleic acid molecule consisting of a sequence with at least 90% sequence identity to SEQ ID NO: 100. In one aspect of any of the embodiments, described herein is a nucleic acid molecule consisting of a sequence with at least 95% sequence identity to SEQ ID NO: 100. In one aspect of any of the embodiments, described herein is a nucleic acid molecule consisting of a sequence with at least 98% sequence identity to SEQ ID NO: 100. In one aspect of any of the embodiments, described herein is a nucleic acid molecule consisting of a sequence with at least 99% sequence identity to SEQID NO: 100. In one aspect of any of the embodiments, described herein is a nucleic acid molecule consisting of a sequence identical to SEQ ID NO: 100.

[0170] In one aspect of any of the embodiments, described herein is a nucleic acid molecule comprising a sequence with at least 80% sequence identity to SEQ ID NO: 101. In one aspect of any of the embodiments, described herein is a nucleic acid molecule comprising a sequence with at least 85% sequence identity to SEQ ID NO: 101. In one aspect of any of the embodiments, described herein is a nucleic acid molecule comprising a sequence with at least 90% sequence identity to SEQ ID NO: 101. In one aspect of any of the embodiments, described herein is a nucleic acid molecule comprising a sequence with at least 95% sequence identity to SEQ ID NO: 101. In one aspect of any of the embodiments, described herein is a nucleic acid molecule comprising a sequence with at least 98% sequence identity to SEQ ID NO: 101. In one aspect of any of the embodiments, described herein is a nucleic acid molecule comprising a sequence with at least 99% sequence identity to SEQ ID NO: 101. In one aspect of any of the embodiments, described herein is a nucleic acid molecule comprising a sequence identical to SEQ ID NO: 101.

[0171] In one aspect of any of the embodiments, described herein is a nucleic acid molecule consisting of a sequence with at least 80% sequence identity to SEQ ID NO: 101. In one aspect of any of the embodiments, described herein is a nucleic acid molecule consisting of a sequence with at least 85% sequence identity to SEQ ID NO: 101. In one aspect of any of the embodiments, described herein is a nucleic acid molecule consisting of a sequence with at least 90% sequence identity to SEQ ID NO: 101. In one aspect of any of the embodiments, described herein is a nucleic acid molecule consisting of a sequence with at least 95% sequence identity to SEQ ID NO: 101. In one aspect of any of the embodiments, described herein is a nucleic acid molecule consisting of a sequence with at least 98% sequence identity to SEQ ID NO: 101. In one aspect of any of the embodiments, described herein is a nucleic acid molecule consisting of a sequence with at least 99% sequence identity to SEQ ID NO: 101. In one aspect of any of the embodiments, described herein is a nucleic acid molecule consisting of a sequence identical to SEQ ID NO: 101.

[0172] In one aspect of any of the embodiments, described herein is a nucleic acid molecule comprising a sequence with at least 80% sequence identity to SEQ ID NO: 102. In one aspect of any of the embodiments, described herein is a nucleic acid molecule comprising a sequence with at least 85% sequence identity to SEQ ID NO: 102. In one aspect of any of the embodiments, described herein is a nucleic acid molecule comprising a sequence with at least 90% sequence identity to SEQ ID NO: 102. In one aspect of any of the embodiments, described herein is a nucleic acid molecule comprising a sequence with at least 95% sequence identity to SEQ ID NO: 102. In one aspect of any of the embodiments, described herein is a nucleic acid molecule comprising a sequence with at least 98% sequence identity to SEQ ID NO: 102. In one aspect of any of the embodiments, described herein is a nucleic acid molecule comprising a sequence with at least 99% sequence identity to SEQID NO: 102. In one aspect of any of the embodiments, described herein is a nucleic acid molecule comprising a sequence identical to SEQ ID NO: 102.

[0173] In one aspect of any of the embodiments, described herein is a nucleic acid molecule consisting of a sequence with at least 80% sequence identity to SEQ ID NO: 102. In one aspect of any of the embodiments, described herein is a nucleic acid molecule consisting of a sequence with at least 85% sequence identity to SEQ ID NO: 102. In one aspect of any of the embodiments, described herein is a nucleic acid molecule consisting of a sequence with at least 90% sequence identity to SEQ ID NO: 102. In one aspect of any of the embodiments, described herein is a nucleic acid molecule consisting of a sequence with at least 95% sequence identity to SEQ ID NO: 102. In one aspect of any of the embodiments, described herein is a nucleic acid molecule consisting of a sequence with at least 98% sequence identity to SEQ ID NO: 102. In one aspect of any of the embodiments, described herein is a nucleic acid molecule consisting of a sequence with at least 99% sequence identity to SEQ ID NO: 102. In one aspect of any of the embodiments, described herein is a nucleic acid molecule consisting of a sequence identical to SEQ ID NO: 102.

[0174] In one aspect of any of the embodiments, described herein is a nucleic acid molecule comprising a sequence with at least 80% sequence identity to SEQ ID NO: 103. In one aspect of any of the embodiments, described herein is a nucleic acid molecule comprising a sequence with at least 85% sequence identity to SEQ ID NO: 103. In one aspect of any of the embodiments, described herein is a nucleic acid molecule comprising a sequence with at least 90% sequence identity to SEQ ID NO: 103. In one aspect of any of the embodiments, described herein is a nucleic acid molecule comprising a sequence with at least 95% sequence identity to SEQ ID NO: 103. In one aspect of any of the embodiments, described herein is a nucleic acid molecule comprising a sequence with at least 98% sequence identity' to SEQ ID NO: 103. In one aspect of any of the embodiments, described herein is a nucleic acid molecule comprising a sequence with at least 99% sequence identity to SEQ ID NO: 103. In one aspect of any of the embodiments, described herein is a nucleic acid molecule comprising a sequence identical to SEQ ID NO: 103.

[0175] In one aspect of any of the embodiments, described herein is a nucleic acid molecule consisting of a sequence with at least 80% sequence identity to SEQ ID NO: 103. In one aspect of any of the embodiments, described herein is a nucleic acid molecule consisting of a sequence with at least 85% sequence identity to SEQ ID NO: 103. In one aspect of any of the embodiments, described herein is a nucleic acid molecule consisting of a sequence with at least 90% sequence identity to SEQ ID NO: 103. In one aspect of any of the embodiments, described herein is a nucleic acid molecule consisting of a sequence with at least 95% sequence identity to SEQ ID NO: 103. In one aspect of any of the embodiments, described herein is a nucleic acid molecule consisting of a sequence with at least 98% sequence identity to SEQ ID NO: 103. In one aspect of any of the embodiments, described herein is a nucleic acid molecule consisting of a sequence with at least 99% sequence identity to SEQID NO: 103. In one aspect of any of the embodiments, described herein is a nucleic acid molecule consisting of a sequence identical to SEQ ID NO: 103.

[0176] In one aspect of any of the embodiments, described herein is a polypeptide comprising a sequence with at least 80% sequence identity to a polypeptide encoded by one of SEQ ID NOs: 100- 111. In one aspect of any of the embodiments, described herein is a polypeptide comprising a sequence with at least 85% sequence identity to a polypeptide encoded by one of SEQ ID NOs: 100- 111. In one aspect of any of the embodiments, described herein is a polypeptide comprising a sequence with at least 90% sequence identity to a polypeptide encoded by one of SEQ ID NOs: 100- 111. In one aspect of any of the embodiments, described herein is a polypeptide comprising a sequence with at least 95% sequence identity to a polypeptide encoded by one of SEQ ID NOs: 100- 111. In one aspect of any of the embodiments, described herein is a polypeptide comprising a sequence with at least 98% sequence identity to a polypeptide encoded by one of SEQ ID NOs: 100- 111. In one aspect of any of the embodiments, described herein is a polypeptide comprising a sequence with at least 99% sequence identity to a polypeptide encoded by one of SEQ ID NOs: 100- 111. In one aspect of any of the embodiments, described herein is a polypeptide comprising a sequence identical to a polypeptide encoded by one of SEQ ID NOs: 100-111.

[0177] In some embodiments of any of the aspects, a nucleic acid molecule described herein does not comprise the sequence of SEQ ID NO: 112. In some embodiments of any of the aspects, a nucleic acid molecule described herein does not comprise the sequence of SEQ ID NO: 113. In some embodiments of any of the aspects, a nucleic acid molecule described herein does not comprise the sequence of SEQ ID NO: 112 or the sequence of SEQ ID NO: 113.

[0178] G3 ( SEQ ID NO : 100 )ATGGCCAAGTACGGCGAGCACGAGGCCAGCCCCGACAACGGCCAGAACGAGTTCAGCGACATCATCAA GAGCCGGAGCGACGAGCACAACGACGTGCAGAAGAAGACCTTCACCAAGTGGATCAACGCCCGGTTCA GCAAGAGCGGCAAGCCCCCCATCAACGACATGTTCACCGACCTGAAGGACGGCCGGAAGCTGCTGGAC CTGCTGGAGGGCCTGACCGGCACCAGCCTGCCCAAGGAGCGGGGCAGCACCCGGGTGCACGCCCTGAA CAACGTGAACCGGGTGCTGCAGGTGCTGCACCAGAACAACGTGGAGCTGGTGAACATCGGCGGCACCG ACATCGTGGACGGCAACCACAAGCTGACCCTGGGCCTGCTGTGGAGCATCATCCTGCACTGGCAGGTG AAGGACGTGATGAAGGACGTGATGAGCGACCTGCAGCAGACCAACAGCGAGAAGATCCTGCTGAGCTG GGTGCGGCAGACCACCCGGCCCTACAGCCAGGTGAACGTGCTGAACTTCACCACCAGCTGGACCGACG GCCTGGCCTTCAACGCCGTGCTGCACCGGCACAAGCCCGACCTGTTCAGCTGGGACAAGGTGGTGAAG ATGAGCCCCATCGAGCGGCTGGAGCACGCCTTCAGCAAGGCCCAGACCTACCTGGGCATCGAGAAGCT GCTGGACCCCGAGGACGTGGCCGTGCAGCTGCCCGACAAGAAGAGCATCATCATGTACCTGACCAGCC TGTTCGAGGTGCTGCCCCAGCAGGTGACCATCGACGCCATCCGGGAGGTGGAGACCCTGCCCCGGAAG TACAAGAAGGAGTGCGAGGAGGAGGCCATCAACATCCAGAGCACCGCCCCCGAGGAGGAGCACGAGAG CCCCCGGGCCGAGACCCCCAGCACCGTGACCGAGGTGGACATGGACCTGGACAGCTACCAGATCGCCC TGGAGGAGGTGCTGACCTGGCTGCTGAGCGCCGAGGACACCTTCCAGGAGCAGGACGACATCAGCGAC GACGTGGAGGAGGTGAAGGACCAGTTCGCCACCCACGAGGCCTTCATGATGGAGCTGACCGCCCACCA GAGCAGCGTGGGCAGCGTGCTGCAGGCCGGCAACCAGCTGATCACCCAGGGCACCCTGAGCGACGAGG AGGAGTTCGAGATCCAGGAGCAGATGACCCTGCTGAACGCCCGGTGGGAGGCCCTGCGGGTGGAGAGC ATGGACCGGCAGAGCCGGCTGCACGACGTGCTGATGGAGCTGCAGAAGAAGCAGCTGCAGCAGCTGAG CGCCTGGCTGACCCTGACCGAGGAGCGGATCCAGAAGATGGAGACCTGCCCCCTGGACGACGACGTGA AGAGCCTGCAGAAGCTGCTGGAGGAGCACAAGAGCCTGCAGAGCGACCTGGAGGCCGAGCAGGTGAAGGTGAACAGCCTGACCCACATGGTGGTGATCGTGGACGAGAACAGCGGCGAGAGCGCCACCGCCATCCTGGAGGACCAGCTGCAGAAGCTGGGCGAGCGGTGGACCGCCGTGTGCCGGTGGACCGAGGAGCGGTGGA ACCGGCTGCAGGAGATCAACATCCTGTGGCAGGAGCTGCTGGAGGAGCAGTGCCTGCTGAAGGCCTGG CTGACCGAGAAGGAGGAGGCCCTGAACAAGGTGCAGACCAGCAACTTCAAGGACCAGAAGGAGCTGAGCGTGAGCGTGCGGCGGCTGGCCATCCTGAAGGAGGACATGGAGATGAAGCGGCAGACCCTGGACCAGCTGAGCGAGATCGGCCAGGACGTGGGCCAGCTGCTGGACAACAGCAAGGCCAGCAAGAAGATCAACAGCGACAGCGAGGAGCTGACCCAGCGGTGGGACAGCCTGGTGCAGCGGCTGGAGGACAGCAGCAACCAGGTGACCCAGGCCGTGGCCAAGCTGGGCATGAGCCAGATCCCCCAGAAGGACCTGCTGGAGACCGTGCGGGTGCGGGAGCAGGCCATCACCAAGAAGAGCAAGCAGGAGCTGCCCCCCCCCCCCCCCCCCAAGAAGCGGCAGATCCACGTGGACCTGGAGAAGCTGCGGGACCTGCAGGGCGCCATGGACGACCTGGACGCCGACATGAAGGAGGCCGAGAGCGTGCGGAACGGCTGGAAGCCCGTGGGCGACCTGCTGATCGACAGCCTGCAGGACCACATCGAGAAGATCATGGCCTTCCGGGAGGAGATCGCCCCCATCAACTTCAAGGTGAAGACCGTGAACGACCTGAGCAGCCAGCTGAGCCCCCTGGACCTGCACCCCAGCCTGAAGATGAGCCGGCAGCTGGA CGACCTGAACATGCGGTGGAAGCTGCTGCAGGTGAGCGTGGACGACCGGCTGAAGCAGCTGCAGGAGG CCCACCGGGACTTCGGCCCCAGCAGCCAGCACTTCCTGAGCACCAGCGTGCAGCTGCCCTGGCAGCGGAGCATCAGCCACAACAAGGTGCCCTACTACATCAACCACCAGACCCAGACCACCTGCTGGGACCACCCCAAGATGACCGAGCTGTTCCAGAGCCTGGCCGACCTGAACAACGTGCGGTTCAGCGCCTACCGGACCGCCATCAAGATCCGGCGGCTGCAGAAGGCCCTGTGCCTGGACCTGCTGGAGCTGAGCACCACCAACGAGATCTTCAAGCAGCACAAGCTGAACCAGAACGACCAGCTGCTGAGCGTGCCCGACGTGATCAACTGCCTGACCACCACCTACGACGGCCTGGAGCAGATGCACAAGGACCTGGTGAACGTGCCCCTGTGCGTGGACATGTGCCTGAACTGGCTGCTGAACGTGTACGACACCGGCCGGACCGGCAAGATCCGGGTGCAGAGCCTGAAGATCGGCCTGATGAGCCTGAGCAAGGGCCTGCTGGAGGAGAAGTACCGGTACCTGTTCAAGGAGGT GGCCGGCCCCACCGAGATGTGCGACCAGCGGCAGCTGGGCCTGCTGCTGCACGACGCCATCCAGATCC CCCGGCAGCTGGGCGAGGTGGCCGCCTTCGGCGGCAGCAACATCGAGCCCAGCGTGCGGAGCTGCTTCCAGCAGAACAACAACAAGCCCGAGATCAGCGTGAAGGAGTTCATCGACTGGATGCACCTGGAGCCCCA GAGCATGGTGTGGCTGCCCGTGCTGCACCGGGTGGCCGCCGCCGAGACCGCCAAGCACCAGGCCAAGT GCAACATCTGCAAGGAGTGCCCCATCGTGGGCTTCCGGTACCGGAGCCTGAAGCACTTCAACTACGACGTGTGCCAGAGCTGCTTCTTCAGCGGCCGGACCGCCAAGGGCCACAAGCTGCACTACCCCATGGTGGA GTACTGCATCCCCACCACCAGCGGCGAGGACGTGCGGGACTTCACCAAGGTGCTGAAGAACAAGTTCC GGAGCAAGAAGTACTTCGCCAAGCACCCCCGGCTGGGCTACCTGCCCGTGCAGACCGTGCTGGAGGGCGACAAC C T GGAGAC C C AGGC C AT GT GA

[0179] G4 ( SEQ ID NO : 101 )ATGGCCAAGTACGGCGAGCACGAGGCCTCCCCCGACAACGGCCAGAACGAGTTCTCCGACATCATCAA GTCCCGCTCCGACGAGCACAACGACGTGCAGAAGAAGACCTTCACCAAGTGGATCAACGCCCGCTTCT CCAAGTCCGGCAAGCCCCCCATCAACGACATGTTCACCGACCTGAAGGACGGCCGCAAGCTGCTGGACCTGCTGGAGGGCCTGACCGGCACCTCCCTGCCCAAGGAGCGCGGCTCCACCCGCGTGCACGCCCTGAACAACGTGAACCGCGTGCTGCAGGTGCTGCACCAGAACAACGTGGAGCTGGTGAACATCGGCGGCACCGACATCGTGGACGGCAACCACAAGCTGACCCTGGGCCTGCTGTGGTCCATCATCCTGCACTGGCAGGTGAAGGACGTGATGAAGGACGTGATGTCCGACCTGCAGCAGACCAACTCCGAGAAGATCCTGCTGTCCTG GGTGCGCCAGACCACCCGCCCCTACTCCCAGGTGAACGTGCTGAACTTCACCACCTCCTGGACCGACG GCCTGGCCTTCAACGCCGTGCTGCACCGCCACAAGCCCGACCTGTTCTCCTGGGACAAGGTGGTGAAGATGTCCCCCATCGAGCGCCTGGAGCACGCCTTCTCCAAGGCCCAGACCTACCTGGGCATCGAGAAGCT GCTGGACCCCGAGGACGTGGCCGTGCAGCTGCCCGACAAGAAGTCCATCATCATGTACCTGACCTCCC TGTTCGAGGTGCTGCCCCAGCAGGTGACCATCGACGCCATCCGCGAGGTGGAGACCCTGCCCCGCAAGTACAAGAAGGAGTGCGAGGAGGAGGCCATCAACATCCAGTCCACCGCCCCCGAGGAGGAGCACGAGTCCCCCCGCGCCGAGACCCCCTCCACCGTGACCGAGGTGGACATGGACCTGGACTCCTACCAGATCGCCCTGGAGGAGGTGCTGACCTGGCTGCTGTCCGCCGAGGACACCTTCCAGGAGCAGGACGACATCTCCGACGACGTGGAGGAGGTGAAGGACCAGTTCGCCACCCACGAGGCCTTCATGATGGAGCTGACCGCCCACCAGTCCTCCGTGGGCTCCGTGCTGCAGGCCGGCAACCAGCTGATCACCCAGGGCACCCTGTCCGACGAGGAGGAGTTCGAGATCCAGGAGCAGATGACCCTGCTGAACGCCCGCTGGGAGGCCCTGCGCGTGGAGTCCATGGACCGCCAGTCCCGCCTGCACGACGTGCTGATGGAGCTGCAGAAGAAGCAGCTGCAGCAGCTGTC CGCCTGGCTGACCCTGACCGAGGAGCGCATCCAGAAGATGGAGACCTGCCCCCTGGACGACGACGTGA AGTCCCTGCAGAAGCTGCTGGAGGAGCACAAGTCCCTGCAGTCCGACCTGGAGGCCGAGCAGGTGAAGGTGAACTCCCTGACCCACATGGTGGTGATCGTGGACGAGAACTCCGGCGAGTCCGCCACCGCCATCCTGGAGGACCAGCTGCAGAAGCTGGGCGAGCGCTGGACCGCCGTGTGCCGCTGGACCGAGGAGCGCTGGA ACCGCCTGCAGGAGATCAACATCCTGTGGCAGGAGCTGCTGGAGGAGCAGTGCCTGCTGAAGGCCTGG CTGACCGAGAAGGAGGAGGCCCTGAACAAGGTGCAGACCTCCAACTTCAAGGACCAGAAGGAGCTGTCCGTGTCCGTGCGCCGCCTGGCCATCCTGAAGGAGGACATGGAGATGAAGCGCCAGACCCTGGACCAGCTGTCCGAGATCGGCCAGGACGTGGGCCAGCTGCTGGACAACTCCAAGGCCTCCAAGAAGATCAACTCCGACTCCGAGGAGCTGACCCAGCGCTGGGACTCCCTGGTGCAGCGCCTGGAGGACTCCTCCAACCAGGTGACCCAGGCCGTGGCCAAGCTGGGCATGTCCCAGATCCCCCAGAAGGACCTGCTGGAGACCGTGCGCG TGCGCGAGCAGGCCATCACCAAGAAGTCCAAGCAGGAGCTGCCCCCCCCCCCCCCCCCCAAGAAGCGC CAGATCCACGTGGACCTGGAGAAGCTGCGCGACCTGCAGGGCGCCATGGACGACCTGGACGCCGACATGAAGGAGGCCGAGTCCGTGCGCAACGGCTGGAAGCCCGTGGGCGACCTGCTGATCGACTCCCTGCAGGACCACATCGAGAAGATCATGGCCTTCCGCGAGGAGATCGCCCCCATCAACTTCAAGGTGAAGACCGTGAACGACCTGTCCTCCCAGCTGTCCCCCCTGGACCTGCACCCCTCCCTGAAGATGTCCCGCCAGCTGGA CGACCTGAACATGCGCTGGAAGCTGCTGCAGGTGTCCGTGGACGACCGCCTGAAGCAGCTGCAGGAGG CCCACCGCGACTTCGGCCCCTCCTCCCAGCACTTCCTGTCCACCTCCGTGCAGCTGCCCTGGCAGCGCTCCATCTCCCACAACAAGGTGCCCTACTACATCAACCACCAGACCCAGACCACCTGCTGGGACCACCCCAAGATGACCGAGCTGTTCCAGTCCCTGGCCGACCTGAACAACGTGCGCTTCTCCGCCTACCGCACCGCCATCAAGATCCGCCGCCTGCAGAAGGCCCTGTGCCTGGACCTGCTGGAGCTGTCCACCACCAACGAGATCTTCAAGCAGCACAAGCTGAACCAGAACGACCAGCTGCTGTCCGTGCCCGACGTGATCAACTGCCTGACCACCACCTACGACGGCCTGGAGCAGATGCACAAGGACCTGGTGAACGTGCCCCTGTGCGTGGACATGTGCCTGAACTGGCTGCTGAACGTGTACGACACCGGCCGCACCGGCAAGATCCGCGTGCAGTCCCTGAAGATCGGCCTGATGTCCCTGTCCAAGGGCCTGCTGGAGGAGAAGTACCGCTACCTGTTCAAGGAGGT GGCCGGCCCCACCGAGATGTGCGACCAGCGCCAGCTGGGCCTGCTGCTGCACGACGCCATCCAGATCC CCCGCCAGCTGGGCGAGGTGGCCGCCTTCGGCGGCTCCAACATCGAGCCCTCCGTGCGCTCCTGCTTCCAGCAGAACAACAACAAGCCCGAGATCTCCGTGAAGGAGTTCATCGACTGGATGCACCTGGAGCCCCA GTCCATGGTGTGGCTGCCCGTGCTGCACCGCGTGGCCGCCGCCGAGACCGCCAAGCACCAGGCCAAGT GCAACATCTGCAAGGAGTGCCCCATCGTGGGCTTCCGCTACCGCTCCCTGAAGCACTTCAACTACGACGTGTGCCAGTCCTGCTTCTTCTCCGGCCGCACCGCCAAGGGCCACAAGCTGCACTACCCCATGGTGGA GTACTGCATCCCCACCACCTCCGGCGAGGACGTGCGCGACTTCACCAAGGTGCTGAAGAACAAGTTCC GCTCCAAGAAGTACTTCGCCAAGCACCCCCGCCTGGGCTACCTGCCCGTGCAGACCGTGCTGGAGGGCGACAAC C T GGAGAC C C AGGC C AT GT GA

[0180] G5 ( SEQ ID NO : 102 )ATGGCCAAGTACGGCGAGCACGAGGCCTCCCCTGACAACGGCCAGAACGAGTTCTCCGACATCATCAA GTCCAGGTCCGACGAGCACAACGACGTGCAGAAGAAGACCTTCACCAAGTGGATCAACGCCAGGTTCT CCAAGTCCGGCAAGCCTCCTATCAACGACATGTTCACCGACCTGAAGGACGGCAGGAAGCTGCTGGACCTGCTGGAGGGCCTGACCGGCACCTCCCTGCCTAAGGAGAGGGGCTCCACCAGGGTGCACGCCCTGAACAACGTGAACAGGGTGCTGCAGGTGCTGCACCAGAACAACGTGGAGCTGGTGAACATCGGCGGCACCGACATCGTGGACGGCAACCACAAGCTGACCCTGGGCCTGCTGTGGTCCATCATCCTGCACTGGCAGGTGAAGGACGTGATGAAGGACGTGATGTCCGACCTGCAGCAGACCAACTCCGAGAAGATCCTGCTGTCCTG GGTGAGGCAGACCACCAGGCCTTACTCCCAGGTGAACGTGCTGAACTTCACCACCTCCTGGACCGACG GCCTGGCCTTCAACGCCGTGCTGCACAGGCACAAGCCTGACCTGTTCTCCTGGGACAAGGTGGTGAAGATGTCCCCTATCGAGAGGCTGGAGCACGCCTTCTCCAAGGCCCAGACCTACCTGGGCATCGAGAAGCT GCTGGACCCTGAGGACGTGGCCGTGCAGCTGCCTGACAAGAAGTCCATCATCATGTACCTGACCTCCC TGTTCGAGGTGCTGCCTCAGCAGGTGACCATCGACGCCATCAGGGAGGTGGAGACCCTGCCTAGGAAGTACAAGAAGGAGTGCGAGGAGGAGGCCATCAACATCCAGTCCACCGCCCCTGAGGAGGAGCACGAGTCCCCTAGGGCCGAGACCCCTTCCACCGTGACCGAGGTGGACATGGACCTGGACTCCTACCAGATCGCCCTGGAGGAGGTGCTGACCTGGCTGCTGTCCGCCGAGGACACCTTCCAGGAGCAGGACGACATCTCCGACGACGTGGAGGAGGTGAAGGACCAGTTCGCCACCCACGAGGCCTTCATGATGGAGCTGACCGCCCACCAGTCCTCCGTGGGCTCCGTGCTGCAGGCCGGCAACCAGCTGATCACCCAGGGCACCCTGTCCGACGAGGAGGAGTTCGAGATCCAGGAGCAGATGACCCTGCTGAACGCCAGGTGGGAGGCCCTGAGGGTGGAGTCCATGGACAGGCAGTCCAGGCTGCACGACGTGCTGATGGAGCTGCAGAAGAAGCAGCTGCAGCAGCTGTC CGCCTGGCTGACCCTGACCGAGGAGAGGATCCAGAAGATGGAGACCTGCCCTCTGGACGACGACGTGA AGTCCCTGCAGAAGCTGCTGGAGGAGCACAAGTCCCTGCAGTCCGACCTGGAGGCCGAGCAGGTGAAGGTGAACTCCCTGACCCACATGGTGGTGATCGTGGACGAGAACTCCGGCGAGTCCGCCACCGCCATCCT GGAGGACCAGCTGCAGAAGCTGGGCGAGAGGTGGACCGCCGTGTGCAGGTGGACCGAGGAGAGGTGGA ACAGGCTGCAGGAGATCAACATCCTGTGGCAGGAGCTGCTGGAGGAGCAGTGCCTGCTGAAGGCCTGGCTGACCGAGAAGGAGGAGGCCCTGAACAAGGTGCAGACCTCCAACTTCAAGGACCAGAAGGAGCTGTCCGTGTCCGTGAGGAGGCTGGCCATCCTGAAGGAGGACATGGAGATGAAGAGGCAGACCCTGGACCAGCTGTCCGAGATCGGCCAGGACGTGGGCCAGCTGCTGGACAACTCCAAGGCCTCCAAGAAGATCAACTCCGACTCCGAGGAGCTGACCCAGAGGTGGGACTCCCTGGTGCAGAGGCTGGAGGACTCCTCCAACCAGGTGACCCAGGCCGTGGCCAAGCTGGGCATGTCCCAGATCCCTCAGAAGGACCTGCTGGAGACCGTGAGGG TGAGGGAGCAGGCCATCACCAAGAAGTCCAAGCAGGAGCTGCCTCCTCCTCCTCCTCCTAAGAAGAGG CAGATCCACGTGGACCTGGAGAAGCTGAGGGACCTGCAGGGCGCCATGGACGACCTGGACGCCGACATGAAGGAGGCCGAGTCCGTGAGGAACGGCTGGAAGCCTGTGGGCGACCTGCTGATCGACTCCCTGCAGG ACCACATCGAGAAGATCATGGCCTTCAGGGAGGAGATCGCCCCTATCAACTTCAAGGTGAAGACCGTG AACGACCTGTCCTCCCAGCTGTCCCCTCTGGACCTGCACCCTTCCCTGAAGATGTCCAGGCAGCTGGACGACCTGAACATGAGGTGGAAGCTGCTGCAGGTGTCCGTGGACGACAGGCTGAAGCAGCTGCAGGAGGCCCACAGGGACTTCGGCCCTTCCTCCCAGCACTTCCTGTCCACCTCCGTGCAGCTGCCTTGGCAGAGGTCCATCTCCCACAACAAGGTGCCTTACTACATCAACCACCAGACCCAGACCACCTGCTGGGACCACCCTAAGATGACCGAGCTGTTCCAGTCCCTGGCCGACCTGAACAACGTGAGGTTCTCCGCCTACAGGACCGCCATCAAGATCAGGAGGCTGCAGAAGGCCCTGTGCCTGGACCTGCTGGAGCTGTCCACCACCAACGAGATCTTCAAGCAGCACAAGCTGAACCAGAACGACCAGCTGCTGTCCGTGCCTGACGTGATCAACTGCCTGACCACCACCTACGACGGCCTGGAGCAGATGCACAAGGACCTGGTGAACGTGCCTCTGTGCGTGGACA TGTGCCTGAACTGGCTGCTGAACGTGTACGACACCGGCAGGACCGGCAAGATCAGGGTGCAGTCCCTG AAGATCGGCCTGATGTCCCTGTCCAAGGGCCTGCTGGAGGAGAAGTACAGGTACCTGTTCAAGGAGGTGGCCGGCCCTACCGAGATGTGCGACCAGAGGCAGCTGGGCCTGCTGCTGCACGACGCCATCCAGATCC CTAGGCAGCTGGGCGAGGTGGCCGCCTTCGGCGGCTCCAACATCGAGCCTTCCGTGAGGTCCTGCTTC CAGCAGAACAACAACAAGCCTGAGATCTCCGTGAAGGAGTTCATCGACTGGATGCACCTGGAGCCTCAGTCCATGGTGTGGCTGCCTGTGCTGCACAGGGTGGCCGCCGCCGAGACCGCCAAGCACCAGGCCAAGTGCAACATCTGCAAGGAGTGCCCTATCGTGGGCTTCAGGTACAGGTCCCTGAAGCACTTCAACTACGACGTGTGCCAGTCCTGCTTCTTCTCCGGCAGGACCGCCAAGGGCCACAAGCTGCACTACCCTATGGTGGA GTACTGCATCCCTACCACCTCCGGCGAGGACGTGAGGGACTTCACCAAGGTGCTGAAGAACAAGTTCA GGTCCAAGAAGTACTTCGCCAAGCACCCTAGGCTGGGCTACCTGCCTGTGCAGACCGTGCTGGAGGGCGACAAC C T GGAGAC C C AGGC C AT GT GA

[0181] G6 ( SEQ ID NO : 103 )ATGGCCAAGTACGGCGAGCACGAGGCCTCCCCCGACAACGGCCAGAACGAGTTCTCCGACATCATCAA GTCCAGGTCCGACGAGCACAACGACGTGCAGAAGAAGACCTTCACCAAGTGGATCAACGCCAGGTTCT CCAAGTCCGGCAAGCCCCCCATCAACGACATGTTCACCGACCTGAAGGACGGCAGGAAGCTGCTGGACCTGCTGGAGGGCCTGACCGGCACCTCCCTGCCCAAGGAGAGGGGCTCCACCAGGGTGCACGCCCTGAACAACGTGAACAGGGTGCTGCAGGTGCTGCACCAGAACAACGTGGAGCTGGTGAACATCGGCGGCACCGACATCGTGGACGGCAACCACAAGCTGACCCTGGGCCTGCTGTGGTCCATCATCCTGCACTGGCAGGTGAAGGACGTGATGAAGGACGTGATGTCCGACCTGCAGCAGACCAACTCCGAGAAGATCCTGCTGTCCTG GGTGAGGCAGACCACCAGGCCCTACTCCCAGGTGAACGTGCTGAACTTCACCACCTCCTGGACCGACG GCCTGGCCTTCAACGCCGTGCTGCACAGGCACAAGCCCGACCTGTTCTCCTGGGACAAGGTGGTGAAGATGTCCCCCATCGAGAGGCTGGAGCACGCCTTCTCCAAGGCCCAGACCTACCTGGGCATCGAGAAGCT GCTGGACCCCGAGGACGTGGCCGTGCAGCTGCCCGACAAGAAGTCCATCATCATGTACCTGACCTCCC TGTTCGAGGTGCTGCCCCAGCAGGTGACCATCGACGCCATCAGGGAGGTGGAGACCCTGCCCAGGAAGTACAAGAAGGAGTGCGAGGAGGAGGCCATCAACATCCAGTCCACCGCCCCCGAGGAGGAGCACGAGTCCCCCAGGGCCGAGACCCCCTCCACCGTGACCGAGGTGGACATGGACCTGGACTCCTACCAGATCGCCCTGGAGGAGGTGCTGACCTGGCTGCTGTCCGCCGAGGACACCTTCCAGGAGCAGGACGACATCTCCGAC GACGTGGAGGAGGTGAAGGACCAGTTCGCCACCCACGAGGCCTTCATGATGGAGCTGACCGCCCACCA GTCCTCCGTGGGCTCCGTGCTGCAGGCCGGCAACCAGCTGATCACCCAGGGCACCCTGTCCGACGAGGAGGAGTTCGAGATCCAGGAGCAGATGACCCTGCTGAACGCCAGGTGGGAGGCCCTGAGGGTGGAGTCCATGGACAGGCAGTCCAGGCTGCACGACGTGCTGATGGAGCTGCAGAAGAAGCAGCTGCAGCAGCTGTC CGCCTGGCTGACCCTGACCGAGGAGAGGATCCAGAAGATGGAGACCTGCCCCCTGGACGACGACGTGAAGTCCCTGCAGAAGCTGCTGGAGGAGCACAAGTCCCTGCAGTCCGACCTGGAGGCCGAGCAGGTGAAGGTGAACTCCCTGACCCACATGGTGGTGATCGTGGACGAGAACTCCGGCGAGTCCGCCACCGCCATCCT GGAGGACCAGCTGCAGAAGCTGGGCGAGAGGTGGACCGCCGTGTGCAGGTGGACCGAGGAGAGGTGGA ACAGGCTGCAGGAGATCAACATCCTGTGGCAGGAGCTGCTGGAGGAGCAGTGCCTGCTGAAGGCCTGGCTGACCGAGAAGGAGGAGGCCCTGAACAAGGTGCAGACCTCCAACTTCAAGGACCAGAAGGAGCTGTCCGTGTCCGTGAGGAGGCTGGCCATCCTGAAGGAGGACATGGAGATGAAGAGGCAGACCCTGGACCAGCTGTCCGAGATCGGCCAGGACGTGGGCCAGCTGCTGGACAACTCCAAGGCCTCCAAGAAGATCAACTCCGACTCCGAGGAGCTGACCCAGAGGTGGGACTCCCTGGTGCAGAGGCTGGAGGACTCCTCCAACCAGGTGACCCAGGCCGTGGCCAAGCTGGGCATGTCCCAGATCCCCCAGAAGGACCTGCTGGAGACCGTGAGGG TGAGGGAGCAGGCCATCACCAAGAAGTCCAAGCAGGAGCTGCCCCCCCCCCCCCCCCCCAAGAAGAGG CAGATCCACGTGGACCTGGAGAAGCTGAGGGACCTGCAGGGCGCCATGGACGACCTGGACGCCGACATGAAGGAGGCCGAGTCCGTGAGGAACGGCTGGAAGCCCGTGGGCGACCTGCTGATCGACTCCCTGCAGG ACCACATCGAGAAGATCATGGCCTTCAGGGAGGAGATCGCCCCCATCAACTTCAAGGTGAAGACCGTG AACGACCTGTCCTCCCAGCTGTCCCCCCTGGACCTGCACCCCTCCCTGAAGATGTCCAGGCAGCTGGACGACCTGAACATGAGGTGGAAGCTGCTGCAGGTGTCCGTGGACGACAGGCTGAAGCAGCTGCAGGAGGCCCACAGGGACTTCGGCCCCTCCTCCCAGCACTTCCTGTCCACCTCCGTGCAGCTGCCCTGGCAGAGGTCCATCTCCCACAACAAGGTGCCCTACTACATCAACCACCAGACCCAGACCACCTGCTGGGACCACCCCAAGATGACCGAGCTGTTCCAGTCCCTGGCCGACCTGAACAACGTGAGGTTCTCCGCCTACAGGACCGCCATCAAGATCAGGAGGCTGCAGAAGGCCCTGTGCCTGGACCTGCTGGAGCTGTCCACCACCAACGAGATCTTCAAGCAGCACAAGCTGAACCAGAACGACCAGCTGCTGTCCGTGCCCGACGTGATCAACTGCCTGACCACCACCTACGACGGCCTGGAGCAGATGCACAAGGACCTGGTGAACGTGCCCCTGTGCGTGGACA TGTGCCTGAACTGGCTGCTGAACGTGTACGACACCGGCAGGACCGGCAAGATCAGGGTGCAGTCCCTG AAGATCGGCCTGATGTCCCTGTCCAAGGGCCTGCTGGAGGAGAAGTACAGGTACCTGTTCAAGGAGGTGGCCGGCCCCACCGAGATGTGCGACCAGAGGCAGCTGGGCCTGCTGCTGCACGACGCCATCCAGATCC CCAGGCAGCTGGGCGAGGTGGCCGCCTTCGGCGGCTCCAACATCGAGCCCTCCGTGAGGTCCTGCTTC CAGCAGAACAACAACAAGCCCGAGATCTCCGTGAAGGAGTTCATCGACTGGATGCACCTGGAGCCCCAGTCCATGGTGTGGCTGCCCGTGCTGCACAGGGTGGCCGCCGCCGAGACCGCCAAGCACCAGGCCAAGTGCAACATCTGCAAGGAGTGCCCCATCGTGGGCTTCAGGTACAGGTCCCTGAAGCACTTCAACTACGACGTGTGCCAGTCCTGCTTCTTCTCCGGCAGGACCGCCAAGGGCCACAAGCTGCACTACCCCATGGTGGA GTACTGCATCCCCACCACCTCCGGCGAGGACGTGAGGGACTTCACCAAGGTGCTGAAGAACAAGTTCA GGTCCAAGAAGTACTTCGCCAAGCACCCCAGGCTGGGCTACCTGCCCGTGCAGACCGTGCTGGAGGGCGACAAC C T GGAGAC C C AGGC C AT GT GA

[0182] G7 ( SEQ ID NO : 104 )ATGGCCAAGTATGGGGAGCATGAGGCTAGTCCTGACAATGGGCAGAATGAATTCAGTGACATCATTAA GTCTAGGTCAGATGAGCACAATGATGTACAGAAGAAAACCTTTACTAAATGGATAAATGCCAGGTTTT CAAAGAGTGGGAAACCACCCATCAATGATATGTTCACTGACCTCAAAGATGGCAGGAAGCTATTGGATCTTCTAGAGGGCCTCACAGGTACATCACTGCCAAAGGAAAGGGGTTCCACAAGAGTACATGCATTAAA TAATGTCAACAGGGTGCTGCAGGTTTTACATCAGAACAATGTGGAATTAGTGAATATAGGAGGAACTG ACATAGTGGATGGAAATCACAAACTGACATTGGGGTTACTTTGGAGCATCATTTTGCACTGGCAGGTGAAAGATGTGATGAAGGATGTCATGTCTGACCTGCAGCAGACCAACTCAGAGAAGATCCTGCTCAGCTG GGTGAGGCAGACTACCAGGCCCTACTCTCAAGTCAATGTGCTCAACTTCACCACCAGCTGGACAGATG GCCTGGCCTTTAATGCAGTGCTCCACAGGCATAAACCTGACCTCTTCAGCTGGGATAAAGTTGTCAAAATGTCACCAATTGAGAGACTTGAACATGCTTTCAGCAAGGCTCAAACATATTTGGGAATAGAGAAGCT GTTAGATCCTGAAGATGTTGCAGTTCAGCTTCCAGACAAGAAAAGTATAATTATGTATTTAACTAGTT TGTTTGAGGTGCTACCTCAGCAAGTCACCATAGATGCCATCAGGGAGGTAGAGACCCTCCCAAGGAAATATAAAAAAGAATGTGAGGAAGAGGCTATTAATATACAGAGCACAGCACCTGAGGAGGAGCATGAGAGTCCCAGGGCTGAGACACCTAGCACTGTGACTGAGGTGGACATGGATCTGGATAGCTATCAGATTGCTTTGGAGGAAGTGCTGACCTGGTTGCTTTCTGCAGAAGACACTTTCCAGGAGCAGGATGACATTTCTGATGATGTTGAAGAAGTCAAAGACCAGTTTGCCACCCATGAGGCATTTATGATGGAACTGACTGCCCACCA GTCCTCTGTGGGCTCTGTGCTGCAGGCAGGCAACCAACTGATAACTCAAGGAACACTGTCAGATGAAG AAGAATTTGAGATTCAGGAACAGATGACACTGCTGAATGCTAGATGGGAGGCCCTTAGGGTGGAGAGCATGGACAGGCAGTCCAGGCTGCATGATGTCCTGATGGAACTGCAGAAGAAGCAACTGCAGCAGCTCTC TGCATGGTTAACACTCACTGAGGAGAGGATTCAGAAGATGGAAACTTGCCCCCTGGATGATGATGTCA AATCTCTACAAAAGCTGCTAGAAGAACATAAAAGTTTGCAATCTGACCTTGAGGCTGAACAGGTGAAAGTAAATTCACTAACTCACATGGTGGTGATTGTGGATGAGAACAGTGGTGAGAGTGCTACTGCTATCCT AGAAGACCAGTTACAGAAACTTGGAGAGAGGTGGACAGCAGTATGCAGGTGGACTGAGGAAAGGTGGA ATAGATTACAAGAAATCAATATATTGTGGCAGGAATTATTGGAAGAACAGTGCTTGTTGAAAGCCTGG T T AACT GAAAAAGAAGAGGC T T TAAAT AAAGT C C AGAC AT C CAAC T T C AAAGAC C AAAAGGAAC T AAG TGTGAGTGTAAGAAGGCTGGCTATTTTGAAGGAAGACATGGAAATGAAGAGGCAAACATTGGATCAGC TGAGTGAGATAGGTCAGGATGTGGGACAATTACTTGATAATTCCAAGGCTTCTAAGAAGATCAACTCA GACAGTGAGGAACTGACTCAAAGGTGGGATTCTTTGGTTCAGAGACTAGAAGATTCCTCCAACCAGGT GACTCAGGCTGTGGCAAAGCTGGGGATGTCTCAGATTCCCCAGAAGGACCTTTTGGAGACAGTTAGGG TAAGGGAACAAGCCATTACAAAAAAATCTAAGCAGGAACTGCCACCTCCTCCTCCCCCTAAGAAGAGG CAGATCCATGTGGATTTGGAGAAACTCAGGGACCTGCAGGGAGCCATGGATGACCTGGATGCTGACAT GAAGGAGGCAGAGTCTGTGAGGAATGGTTGGAAGCCAGTGGGGGACTTACTCATAGACAGTCTGCAGG ATCACATTGAGAAAATCATGGCATTTAGGGAGGAAATTGCTCCCATCAACTTTAAAGTTAAAACAGTC AATGATTTATCCAGTCAGCTGTCCCCTCTTGACCTGCATCCCTCTCTAAAGATGTCTAGGCAGCTAGA TGACCTTAATATGAGGTGGAAACTTTTACAGGTTTCTGTGGATGATAGACTTAAACAGCTTCAGGAAG CCCACAGGGATTTTGGGCCCTCTTCCCAGCATTTTCTCTCTACCTCTGTCCAGCTGCCTTGGCAAAGA T C CAT T T C AC AT AAT AAAGT GC C C T AT T AC AT C AAG C AT C AAAC ACAGAC C AC C T GT T GGGAC C ATC C TAAAATGACTGAACTCTTTCAATCCCTTGCTGACCTGAATAATGTGAGGTTTTCTGCCTACAGGACTG CAATCAAAATCAGGAGGCTACAAAAAGCACTATGTTTGGATCTCCTGGAGTTGAGTACAACAAATGAG ATTTTCAAACAGCACAAGTTGAACCAAAATGATCAGCTCCTCAGTGTGCCTGATGTCATCAACTGTCT GACAACAACTTATGATGGACTTGAGCAAATGCATAAGGACCTGGTCAATGTTCCACTCTGTGTGGATA TGTGTCTCAATTGGTTGCTCAATGTCTATGACACAGGTAGGACTGGAAAAATTAGAGTGCAGAGTCTG AAGATTGGCTTAATGTCTCTCTCCAAAGGTCTCTTGGAAGAAAAATACAGATATCTCTTTAAGGAAGT TGCAGGGCCAACTGAGATGTGTGACCAGAGGCAGCTGGGCCTGTTACTTCATGATGCCATCCAGATCC CTAGGCAGCTAGGTGAAGTAGCAGCATTTGGAGGCAGTAATATAGAGCCCTCAGTCAGGAGCTGCTTC CAACAGAATAACAATAAACCTGAAATATCAGTGAAAGAGTTTATAGACTGGATGCATTTGGAACCACA GTCCATGGTTTGGCTCCCTGTGTTACATAGGGTGGCTGCTGCAGAGACTGCCAAACATCAGGCCAAAT GCAACATCTGTAAAGAATGTCCCATTGTGGGTTTCAGGTATAGATCCCTTAAGCATTTTAACTATGAT GTGTGCCAGAGTTGTTTCTTTTCAGGTAGGACAGCAAAAGGTCACAAATTACATTACCCAATGGTGGA GTATTGTATACCTACAACATCAGGAGAGGATGTAAGGGACTTCACTAAGGTACTTAAGAACAAGTTCA GGAGCAAGAAGTACTTTGCCAAACACCCTAGGCTTGGTTACCTGCCAGTCCAGACAGTTCTTGAAGGT GACAACTTAGAGACTCAGGCTATGTGA

[0183] G8 ( SEQ ID NO : 105 )ATGGCTAAGTATGGAGAGCATGAGGCCAGTCCAGACAATGGCCAGAATGAATTCAGTGACATCATTAA GTCCAGGTCTGATGAACACAATGATGTACAGAAGAAAACCTTTACCAAATGGATAAATGCCAGGTTTA GCAAGAGTGGCAAACCACCCATCAATGATATGTTCACTGACCTCAAAGATGGCAGGAAGCTATTGGAT CTTCTAGAAGGCCTCACAGGAACATCACTGCCAAAGGAAAGAGGTTCCACCAGGGTACATGCTTTAAA TAATGTCAACAGGGTGCTGCAGGTTTTACATCAGAACAATGTGGAGTTAGTGAATATAGGAGGAACTG ACATAGTGGATGGCAATCACAAACTGACATTGGGGTTACTTTGGAGCATCATTTTGCACTGGCAGGTG AAAGATGTCATGAAGGATGTAATGTCAGACCTGCAGCAGACCAACAGTGAGAAGATCCTGCTCAGCTG GGTGAGGCAGACAACCAGGCCCTACAGTCAAGTCAATGTCCTCAACTTCACCACCAGCTGGACTGATG GACTGGCATTTAATGCTGTGCTCCACAGGCATAAACCTGACCTCTTCAGCTGGGATAAAGTTGTCAAA ATGTCACCAATTGAGAGGCTTGAACATGCCTTCAGCAAGGCTCAAACTTATTTGGGAATAGAGAAGCT GTTAGACCCAGAAGATGTGGCTGTGCAGCTTCCTGACAAGAAATCAATAATTATGTATTTAACTAGCT TGTTTGAGGTGCTACCACAGCAAGTCACCATAGATGCAATCAGAGAGGTAGAGACCCTCCCAAGGAAA T ATAAAAAAGAAT GT GAGGAAGAGGCCAT T AAT ATACAGT CCACAGCACCAGAGGAGGAGCAT GAGAG TCCCAGGGCTGAAACTCCCAGCACTGTCACTGAGGTTGATATGGATCTGGACAGCTATCAGATTGCAT TGGAGGAAGTGCTGACCTGGTTGCTTTCTGCTGAGGACACTTTCCAGGAGCAGGATGATATTTCTGATGATGTGGAGGAAGTCAAAGACCAGTTTGCTACCCATGAGGCATTTATGATGGAACTGACTGCACACCA GTCTTCTGTTGGGTCAGTGCTGCAGGCAGGTAACCAACTGATAACTCAAGGAACTCTGTCTGATGAAG AAGAATTTGAGATTCAGGAACAGATGACACTGCTGAATGCCAGATGGGAGGCTCTTAGGGTGGAGAGC ATGGACAGGCAGTCCAGGCTGCATGATGTGCTGATGGAACTGCAGAAGAAGCAACTGCAGCAGCTCTC TGCCTGGTTAACACTCACAGAGGAGAGGATTCAGAAGATGGAAACTTGCCCCCTGGATGATGATGTAAAATCTCTACAAAAGCTGCTAGAAGAACATAAAAGTTTGCAAAGTGATCTTGAGGCTGAACAGGTGAAA GTAAATTCACTAACTCACATGGTGGTCATAGTTGATGAGAACTCAGGTGAGAGTGCCACAGCTATCCT AGAAGACCAGTTACAGAAACTGGGTGAGAGATGGACTGCAGTCTGCAGGTGGACAGAAGAAAGGTGGA AT AGGT T ACAAGAAAT CAAT AT AT TGT GGCAGGAAT T ATT GGAAGAACAGT GCT T GT T GAAAGCATGG TTAACTGAAAAAGAAGAGGCTTTAAATAAAGTCCAGACAAGCAACTTCAAAGACCAAAAGGAACTAAG TGTCAGTGTTAGGAGGCTGGCTATTTTGAAGGAAGACATGGAAATGAAGAGACAAACATTGGATCAGC TGAGTGAGATAGGCCAGGATGTGGGACAATTACTTGATAATTCCAAGGCCTCTAAGAAGATCAACTCA GATTCAGAGGAACTGACTCAAAGGTGGGATTCCTTGGTTCAGAGACTAGAAGATTCCTCCAACCAGGT GACTCAGGCAGTAGCAAAGCTGGGGATGTCTCAGATTCCCCAGAAGGACCTTTTGGAGACTGTGAGAG TAAGGGAGCAAGCCATTACAAAAAAATCTAAGCAGGAACTGCCTCCTCCTCCTCCTCCTAAGAAGAGG CAGATCCATGTGGATTTGGAGAAACTCAGGGACCTGCAGGGAGCCATGGATGACCTGGATGCAGACAT GAAGGAGGCAGAGTCTGTGAGGAATGGCTGGAAGCCAGTGGGAGACTTACTCATTGACAGCCTGCAGG ATCACATAGAAAAAATCATGGCATTTAGAGAGGAAATAGCTCCCATCAACTTTAAAGTTAAAACAGTC AATGATTTATCCAGTCAGCTGAGCCCACTTGACCTGCATCCCTCTCTAAAGATGTCTAGACAGCTAGA TGATCTTAATATGAGGTGGAAACTTTTACAGGTTTCTGTGGATGATAGGCTTAAACAGCTTCAGGAAG CCCACAGGGATTTTGGACCATCCTCCCAGCATTTTCTCTCTACCTCTGTCCAGCTGCCCTGGCAAAGA T C CAT T T C AC AT AAT AAAGT GC C C T AT T AC AT C AAC C AT 0 AAAC ACAGAC C AC C T GT T GGGAC C ATC C TAAAATGACTGAGCTCTTTCAATCCCTTGCTGATCTGAATAATGTGAGGTTTTCTGCCTACAGAACAG CCATCAAAATCAGAAGGCTACAAAAAGCACTATGTTTGGATCTCCTGGAGTTGAGTACAACAAATGAA ATTTTCAAACAGCACAAGTTGAACCAAAATGACCAGCTCCTCTCTGTGCCTGATGTGATCAACTGTCT GACAACAACTTATGATGGACTTGAGCAAATGCATAAGGACCTGGTCAATGTCCCTCTCTGTGTTGACA TGTGTCTCAATTGGTTGCTCAATGTGTATGACACAGGTAGAACAGGAAAAATTAGGGTGCAGAGTCTG AAGATTGGATTAATGTCTCTCTCCAAAGGTCTCTTGGAAGAAAAATACAGATATCTCTTTAAGGAAGT TGCTGGCCCAACAGAAATGTGTGACCAGAGGCAGCTGGGCCTGTTACTTCATGATGCTATCCAGATCC CAAGACAGCTAGGTGAAGTAGCTGCATTTGGTGGCAGTAATATAGAGCCTAGTGTGAGGAGCTGCTTC CAACAGAATAACAATAAACCAGAGATATCTGTGAAAGAGTTTATAGATTGGATGCATTTGGAACCACA GTCCATGGTTTGGCTCCCTGTTTTACATAGGGTGGCAGCTGCAGAGACTGCTAAACATCAGGCCAAAT GCAACATCTGTAAAGAATGTCCAATAGTGGGCTTCAGGTATAGGTCCCTTAAGCATTTTAACTATGAT GTTTGCCAGAGTTGTTTCTTTTCAGGCAGGACTGCCAAAGGTCACAAATTACATTACCCAATGGTGGA ATATTGTATACCTACAACATCTGGGGAAGATGTTAGAGACTTCACAAAGGTACTTAAGAACAAGTTCA GGAGCAAGAAGTACTTTGCAAAACACCCTAGGCTTGGTTACCTGCCTGTCCAGACAGTTCTTGAAGGT GACAAC T T AGAGAC T C AGGC AAT GT GA

[0184] G9 ( SEQ ID NO : 106 )ATGGCTAAGTATGGGGAGCATGAGGCCAGTCCAGACAATGGACAGAATGAGTTCAGTGACATCATTAA GTCTAGGTCAGATGAGCACAATGATGTCCAGAAGAAAACCTTTACTAAATGGATAAATGCCAGATTTA GCAAGAGTGGGAAACCACCCATCAATGACATGTTCACTGACCTCAAAGATGGCAGGAAGCTATTGGAT CTTCTAGAGGGCCTCACTGGAACATCACTGCCAAAGGAAAGGGGTTCCACCAGGGTACATGCCTTAAA TAATGTCAACAGGGTGCTGCAGGTTTTACATCAGAACAATGTGGAATTAGTGAATATAGGAGGAACTG ACATAGTGGATGGCAATCACAAACTGACTTTGGGGTTACTTTGGAGCATCATTTTGCACTGGCAGGTG AAAGATGTGATGAAGGATGTGATGTCAGACCTGCAGCAGACCAACTCAGAAAAGATCCTGCTCAGCTG GGTGAGGCAGACAACCAGGCCCTACTCCCAAGTCAATGTCCTCAACTTCACCACCAGCTGGACAGATG GCCTGGCATTTAATGCTGTCCTCCACAGGCATAAACCAGACCTCTTCAGCTGGGATAAAGTTGTCAAA ATGTCACCAATAGAGAGGCTTGAACATGCTTTCAGCAAGGCTCAAACATATTTGGGAATAGAAAAGCT GCTGGATCCTGAAGATGTGGCTGTCCAGCTTCCTGACAAGAAATCAATAATTATGTATTTAACAAGCT TGTTTGAGGTGCTACCACAGCAAGTCACCATAGATGCAATCAGAGAGGTAGAGACCCTCCCAAGGAAA T ATAAAAAAGAAT GT GAAGAAGAGGCT AT T AAT ATACAGT CCACT GCCCCAGAGGAGGAGCAT GAGAG TCCTAGGGCAGAGACCCCAAGCACTGTCACTGAGGTTGATATGGATCTGGATAGCTATCAGATAGCAT TGGAGGAAGTGCTGACCTGGTTGCTTTCAGCTGAGGACACTTTCCAGGAGCAGGATGATATTTCTGAT GATGTGGAGGAAGTCAAAGACCAGTTTGCCACCCATGAGGCATTTATGATGGAACTGACTGCTCACCA GTCCAGTGTGGGCTCTGTTCTGCAGGCAGGGAACCAACTGATAACTCAAGGAACACTGTCTGATGAGG AAGAATTTGAGATTCAGGAACAGATGACTCTGCTGAATGCCAGATGGGAGGCCCTTAGGGTAGAGAGCATGGACAGGCAGTCCAGACTGCATGATGTGCTGATGGAACTGCAGAAGAAGCAACTGCAGCAGCTCTCTGCTTGGTTAACACTCACAGAGGAGAGGATTCAGAAGATGGAAACTTGCCCCCTGGATGATGATGTAA AATCTCTACAAAAGCTGCTAGAAGAACATAAAAGTTTGCAAAGTGACCTTGAGGCAGAGCAGGTGAAA GTAAATTCACTAACTCACATGGTGGTCATTGTTGATGAAAACTCAGGGGAGTCAGCTACAGCTATCCT AGAAGACCAGTTACAGAAATTGGGTGAGAGGTGGACAGCTGTATGCAGGTGGACTGAGGAAAGGTGGA ATAGGTTACAAGAAATCAATATATTGTGGCAGGAATTATTGGAAGAACAGTGCTTGTTGAAAGCTTGG T T AACAGAGAAAGAAGAGGC T T TAAAT AAAGT C C AGAC AT C CAAC T T C AAAGAC C AAAAGGAAC T AAG TGTATCTGTGAGGAGGCTGGCTATTTTGAAGGAAGACATGGAAATGAAGAGACAAACATTGGATCAGC TGTCAGAGATAGGGCAGGATGTGGGACAATTACTTGATAATTCCAAGGCATCTAAGAAGATCAACTCA GACTCAGAGGAACTGACTCAAAGGTGGGATTCCTTGGTTCAGAGACTAGAAGATTCCTCCAACCAGGT GACTCAGGCTGTAGCAAAGCTGGGGATGTCTCAGATTCCACAGAAGGACCTTTTGGAGACTGTCAGGG TAAGGGAGCAAGCCATTACAAAAAAATCTAAGCAGGAACTGCCCCCTCCTCCTCCCCCCAAGAAGAGG CAGATCCATGTGGATTTGGAGAAACTCAGGGACCTGCAGGGTGCCATGGATGACCTGGATGCTGACAT GAAGGAGGCTGAGTCTGTGAGGAATGGGTGGAAGCCAGTTGGGGACTTACTCATAGATAGCCTGCAGG ATCACATAGAGAAAATCATGGCATTTAGAGAAGAAATAGCCCCTATCAACTTTAAAGTTAAAACAGTG AATGACTTATCCAGTCAGCTGTCCCCTCTTGACCTGCATCCCTCTCTAAAGATGTCTAGGCAGCTAGA TGACCTTAATATGAGGTGGAAACTTTTACAGGTTTCTGTGGATGACAGGCTTAAACAGCTTCAGGAAG CCCACAGGGATTTTGGACCATCATCACAGCATTTTCTCTCTACCAGTGTGCAGCTGCCATGGCAAAGA T C CAT T T C AC ATAAT AAAGT GO C C T AT T AC AT C AAC C AT C AAAC ACAGAC C AC C T GT T GGGAC C ATC C TAAAATGACTGAACTCTTTCAATCCCTTGCTGACCTGAATAATGTAAGGTTTTCTGCCTACAGGACAG CCATCAAAATCAGGAGACTACAAAAAGCACTATGTTTGGATCTCCTGGAGTTGAGTACAACAAATGAG ATTTTCAAACAGCACAAGTTGAACCAAAATGATCAGCTCCTCAGTGTCCCTGATGTGATCAACTGTCT GACAACAACTTATGATGGGCTTGAGCAAATGCATAAGGACCTGGTCAATGTGCCTCTCTGTGTGGATA TGTGTCTCAATTGGTTGCTCAATGTATATGATACTGGGAGGACTGGAAAAATTAGGGTGCAGAGTCTG AAGATAGGCTTAATGTCTCTCTCCAAAGGTCTCTTGGAAGAAAAATACAGATATCTCTTTAAGGAAGT GGCAGGGCCAACTGAAATGTGTGATCAGAGGCAGCTGGGCCTGTTACTTCATGATGCCATCCAGATCC CTAGGCAGCTAGGTGAAGTAGCTGCTTTTGGAGGCAGTAATATAGAGCCAAGTGTCAGGAGCTGCTTC CAACAGAATAACAATAAACCTGAAATAAGTGTGAAAGAGTTTATAGACTGGATGCATTTGGAACCACA GTCCATGGTTTGGCTCCCTGTTTTACATAGGGTGGCAGCTGCAGAGACTGCCAAACATCAGGCCAAAT GCAACATCTGTAAAGAATGTCCTATAGTGGGGTTCAGGTATAGATCCCTTAAGCATTTTAACTATGAT GTCTGCCAGAGTTGTTTCTTTTCTGGGAGGACTGCCAAAGGTCACAAATTACATTACCCAATGGTGGA ATATTGTATACCTACAACATCTGGGGAAGATGTTAGGGATTTCACTAAGGTACTTAAGAACAAGTTCA GGTCTAAGAAGTACTTTGCAAAACACCCTAGGCTTGGTTACCTGCCAGTGCAGACAGTCCTTGAAGGT GACAAC T T AGAGAC T C AGGC C AT GT GA

[0185] GI O ( SEQ ID NO : 107 )ATGGCAAAGTATGGGGAGCATGAAGCAAGTCCAGACAATGGACAGAATGAATTCTCAGATATCATTAA GTCCAGGTCTGATGAACACAATGATGTACAGAAGAAAACCTTTACCAAATGGATAAATGCCAGGTTTA GCAAGAGTGGCAAACCACCCATCAATGATATGTTCACTGACCTCAAAGATGGAAGGAAGCTATTGGAT CTTCTGGAAGGCCTCACTGGAACATCACTGCCAAAGGAAAGGGGTTCCACCAGAGTACATGCCTTAAA TAATGTCAACAGGGTGCTGCAGGTTTTACATCAGAACAATGTTGAATTAGTGAATATAGGTGGCACTG ATATAGTTGATGGGAATCACAAACTGACCTTGGGGTTACTTTGGAGCATCATTTTGCACTGGCAGGTG AAAGATGTCATGAAGGATGTGATGTCTGACCTGCAGCAGACAAACAGTGAGAAGATCCTGCTCAGCTG GGTGAGGCAGACCACCAGACCCTACAGCCAAGTCAATGTCCTCAACTTCACCACCAGCTGGACAGATG GCCTGGCTTTTAATGCAGTGCTCCACAGGCATAAACCAGATCTCTTCAGCTGGGATAAAGTTGTCAAA ATGTCACCAATAGAAAGGCTTGAACATGCCTTCAGCAAGGCTCAAACCTATTTGGGAATAGAGAAGCT GTTAGACCCAGAAGATGTTGCAGTCCAGCTTCCTGACAAGAAATCTATAATTATGTATTTAACTTCCT TGTTTGAGGTGCTACCCCAGCAAGTCACCATAGATGCCATCAGGGAGGTAGAGACCCTCCCAAGGAAA TATAAAAAAGAATGTGAGGAAGAGGCCATTAATATACAGAGCACAGCTCCAGAGGAGGAGCATGAGAG TCCAAGGGCTGAGACCCCTAGCACAGTCACTGAGGTGGACATGGATCTGGACAGCTATCAGATTGCCT TGGAGGAAGTGCTGACCTGGTTGCTTTCAGCTGAGGACACTTTCCAGGAGCAGGATGACATTTCTGAT GATGTTGAAGAAGTCAAAGACCAGTTTGCCACCCATGAAGCCTTTATGATGGAACTGACTGCACACCA GTCCAGTGTAGGCTCTGTCCTGCAGGCTGGCAACCAACTGATAACCCAAGGAACCCTGTCTGATGAAG AAGAATTTGAGATTCAGGAACAGATGACTCTGCTGAATGCTAGATGGGAGGCACTTAGGGTGGAGAGT ATGGACAGGCAGTCCAGACTGCATGATGTTCTGATGGAACTGCAGAAGAAGCAACTGCAGCAGCTCTCAGCATGGTTAACACTCACAGAGGAGAGGATTCAGAAGATGGAAACTTGCCCCCTGGATGATGATGTGA AATCTCTACAAAAGCTGCTAGAAGAACATAAAAGTTTGCAATCAGATCTTGAGGCTGAACAGGTGAAA GTAAATTCACTAACTCACATGGTGGTGATTGTGGATGAGAACTCAGGGGAGAGTGCTACAGCAATCCT AGAAGACCAGTTACAGAAACTGGGGGAGAGATGGACAGCAGTCTGCAGGTGGACAGAGGAAAGATGGA ATAGGTTACAAGAAATCAATATATTGTGGCAGGAATTATTGGAAGAACAGTGCTTGTTGAAAGCTTGG TTAACTGAAAAAGAAGAGGCTTTAAATAAAGTCCAGACAAGCAACTTCAAAGACCAAAAGGAACTATC AGTGTCAGTTAGAAGGCTGGCTATTTTGAAGGAAGACATGGAAATGAAGAGGCAAACATTGGATCAGC TGAGTGAGATAGGGCAGGATGTGGGGCAATTACTTGATAATTCCAAGGCATCTAAGAAGATCAACTCT GACTCAGAGGAACTGACTCAAAGGTGGGATTCTTTGGTTCAGAGACTAGAAGATTCCTCCAACCAGGT GACTCAGGCAGTTGCAAAGCTGGGGATGTCTCAGATTCCACAGAAGGACCTTTTGGAGACTGTGAGAG TAAGGGAGCAAGCCATTACAAAAAAATCTAAGCAGGAACTGCCACCTCCTCCTCCTCCTAAGAAGAGA CAGATCCATGTGGATTTGGAGAAACTCAGGGACCTGCAGGGAGCCATGGATGACCTGGATGCTGATAT GAAGGAGGCTGAGTCTGTCAGGAATGGCTGGAAGCCTGTGGGAGACTTACTCATAGATTCCCTGCAGG ATCACATAGAGAAAATCATGGCATTTAGGGAAGAAATTGCTCCTATCAACTTTAAAGTTAAAACAGTG AATGATTTATCCAGTCAGCTGTCTCCTCTTGACCTGCATCCCTCTCTAAAGATGTCTAGGCAGCTAGA TGACCTTAATATGAGATGGAAACTTTTACAGGTTTCTGTTGATGATAGGCTTAAACAGCTTCAGGAAG CCCACAGGGATTTTGGCCCTAGCTCCCAGCATTTTCTCTCTACTTCAGTCCAGCTGCCTTGGCAAAGA T C CAT T T C AC AT AAT AAAGT GO C T T AT T AC AT C AAC C AT C AAAC ACAGAC C AC C T GT T GGGAC C ATC C TAAAATGACTGAGCTCTTTCAATCCCTTGCTGACCTGAATAATGTGAGATTTTCAGCCTACAGGACTG CAATCAAAATCAGGAGGCTACAAAAAGCACTATGTTTGGATCTCCTGGAGTTGAGTACAACAAATGAG ATTTTCAAACAGCACAAGTTGAACCAAAATGACCAGCTCCTCTCTGTCCCAGATGTGATCAACTGTCT GACAACAACTTATGATGGCCTTGAGCAAATGCATAAGGACCTGGTCAATGTCCCTCTCTGTGTGGATA TGTGTCTCAATTGGTTGCTCAATGTCTATGACACTGGTAGAACTGGAAAAATTAGAGTGCAGAGTCTG AAGATTGGGTTAATGTCTCTCTCCAAAGGTCTCTTGGAAGAAAAATACAGATATCTCTTTAAGGAAGT TGCAGGGCCAACAGAAATGTGTGACCAGAGGCAGCTGGGCCTGTTACTTCATGATGCTATCCAGATCC CTAGGCAGCTAGGTGAAGTAGCTGCCTTTGGAGGCAGTAATATAGAGCCTTCTGTGAGGAGCTGCTTC CAACAGAATAACAATAAACCTGAAATAAGTGTGAAAGAGTTTATAGACTGGATGCATTTGGAACCACA GTCCATGGTTTGGCTCCCTGTTTTACATAGGGTGGCAGCAGCTGAGACAGCAAAACATCAGGCCAAAT GCAACATCTGTAAAGAATGTCCTATTGTGGGGTTCAGGTATAGGAGTCTTAAGCATTTTAACTATGAT GTCTGCCAGAGTTGTTTCTTTTCAGGCAGGACTGCCAAAGGTCACAAATTACATTACCCAATGGTGGA ATATTGTATACCTACAACAAGTGGGGAAGATGTCAGGGACTTCACCAAGGTACTTAAGAACAAGTTCA GGTCCAAGAAGTACTTTGCCAAACACCCTAGACTTGGTTACCTGCCTGTCCAGACAGTCCTTGAAGGT GACAAC T T AGAGAC T C AGGC AAT GT GA

[0186] Gi l ( SEQ ID NO : 108 )ATGGCCAAGTATGGGGAACATGAAGCCAGTCCAGACAATGGCCAGAATGAATTCAGTGATATCATTAA GTCCAGATCAGATGAGCACAATGATGTGCAGAAGAAAACCTTTACCAAATGGATAAATGCTAGGTTTT CAAAGTCAGGTAAACCACCCATCAATGACATGTTCACTGACCTCAAAGATGGAAGGAAGCTACTTGAT CTTCTAGAAGGCCTCACAGGAACATCACTGCCTAAGGAAAGAGGTTCCACAAGGGTACATGCCTTAAA TAATGTCAACAGAGTGCTGCAGGTTTTACATCAGAACAATGTGGAATTAGTTAATATTGGGGGCACTG ACATAGTGGATGGCAATCACAAACTGACTTTGGGGTTACTTTGGTCAATCATTTTGCACTGGCAGGTG AAAGATGTCATGAAGGATGTCATGTCAGACCTGCAGCAGACTAACTCTGAGAAGATCCTGCTCAGCTG GGTGAGGCAGACCACCAGGCCATACTCCCAAGTCAATGTGCTCAACTTCACCACCAGCTGGACAGATG GACTGGCCTTTAATGCTGTCCTCCACAGGCATAAACCTGATCTCTTCAGCTGGGATAAAGTTGTCAAA ATGTCACCAATTGAGAGACTTGAACATGCCTTCAGCAAGGCCCAAACATATTTGGGAATAGAAAAGCT GTTAGATCCAGAAGATGTTGCTGTTCAGCTTCCAGACAAGAAATCCATAATTATGTATTTAACATCTT TGTTTGAGGTGCTACCTCAGCAAGTCACCATAGATGCTATCAGGGAGGTAGAGACCCTCCCAAGGAAA T ATAAAAAAGAAT GT GAGGAAGAGGCAAT T AAT ATACAGT CTACT GCT CCT GAGGAGGAGCAT GAGAG TCCCAGAGCAGAAACTCCCAGCACAGTCACAGAGGTTGATATGGATCTGGACAGCTATCAGATTGCTT TGGAGGAAGTGCTGACCTGGTTGCTTAGTGCAGAAGACACCTTCCAGGAGCAGGATGATATTTCAGAT GATGTGGAAGAAGTCAAAGACCAGTTTGCCACCCATGAGGCTTTTATGATGGAACTGACTGCACACCA GAGCTCTGTGGGCAGTGTCCTGCAGGCTGGCAACCAACTGATAACACAAGGAACTCTGTCAGATGAGG AAGAATTTGAGATTCAGGAACAGATGACACTGCTGAATGCTAGATGGGAGGCTCTTAGGGTGGAGAGT ATGGACAGGCAGTCCAGACTGCATGATGTGCTGATGGAACTGCAGAAGAAGCAACTGCAGCAGCTCTCAGCCTGGTTAACACTCACAGAGGAGAGAATTCAGAAGATGGAAACCTGCCCACTGGATGATGATGTGA AATCTCTACAAAAGCTGCTAGAAGAACATAAAAGTTTGCAATCTGACCTTGAGGCTGAACAGGTGAAA GTAAATTCACTAACTCACATGGTGGTCATTGTAGATGAGAACAGTGGGGAGAGTGCCACAGCTATCCT AGAAGACCAGTTACAGAAACTTGGGGAGAGATGGACTGCAGTGTGCAGGTGGACTGAGGAAAGGTGGA AT AGAT T ACAAGAAAT CAAT AT AT TGT GGCAGGAAT T ATT GGAAGAACAGT GCT T GT T GAAAGCT TGG TTAACTGAGAAAGAAGAGGCCTTAAATAAAGTCCAGACTAGCAACTTCAAAGACCAAAAGGAACTAAG TGTGAGTGTTAGGAGGCTGGCTATTTTGAAGGAAGACATGGAAATGAAGAGACAAACTTTGGATCAGC TGAGTGAGATTGGCCAGGATGTAGGGCAATTACTTGACAATTCCAAGGCCTCTAAGAAGATCAACAGT GACTCAGAGGAACTGACTCAAAGATGGGATTCTCTAGTTCAGAGACTGGAAGATTCCTCCAACCAGGT GACTCAGGCTGTGGCTAAGCTGGGGATGAGCCAGATTCCTCAGAAGGACCTTTTGGAAACTGTCAGGG TAAGAGAACAAGCCATTACAAAAAAATCTAAGCAGGAACTGCCTCCTCCTCCCCCCCCAAAGAAGAGG CAGATCCATGTGGATTTGGAAAAACTCAGGGACCTGCAGGGGGCTATGGATGACCTGGATGCTGACAT GAAGGAGGCTGAGTCTGTGAGAAATGGCTGGAAGCCTGTGGGAGACTTACTCATAGATAGCCTGCAGG ATCACATTGAAAAAATCATGGCCTTTAGGGAAGAAATTGCACCTATCAACTTTAAAGTTAAAACTGTT AATGATTTATCCTCACAGCTGAGCCCACTTGACCTGCATCCAAGCCTAAAGATGTCTAGGCAGCTAGA TGATCTTAATATGAGATGGAAACTTTTACAGGTTTCTGTGGATGATAGACTTAAACAGCTTCAGGAAG CCCACAGAGATTTTGGCCCATCCTCTCAGCATTTTCTCTCTACAAGTGTCCAGCTGCCCTGGCAAAGA T C CAT T T C AC ATAAT AAAGT GO C C T AT T AC AT C AAC C AT C AAAC ACAGAC T AC AT GT T GGGAC C ATC C TAAAATGACAGAGCTCTTTCAATCTCTTGCTGACCTGAATAATGTCAGGTTTTCAGCTTACAGAACAG CTATCAAAATCAGGAGGCTACAAAAAGCACTATGTTTGGACCTCTTAGAGTTGAGTACTACAAATGAG ATTTTCAAACAGCACAAGTTGAACCAAAATGACCAGCTCCTCTCTGTCCCTGATGTAATCAACTGTCT GACCACAACATATGATGGCCTTGAGCAAATGCATAAGGACCTGGTCAATGTGCCACTCTGTGTAGATA TGTGTCTCAATTGGTTGCTCAATGTGTATGACACAGGTAGGACTGGAAAAATTAGGGTGCAGAGTCTG AAGATTGGTTTAATGTCTCTCTCTAAAGGTCTCTTGGAAGAAAAATACAGATATCTCTTTAAGGAAGT TGCAGGACCCACAGAAATGTGTGACCAGAGGCAGCTGGGCCTGTTACTTCATGATGCTATCCAGATCC CAAGGCAGCTGGGGGAAGTAGCAGCATTTGGAGGGAGCAATATAGAGCCAAGTGTTAGGAGCTGCTTC CAACAGAATAACAATAAACCAGAAATATCAGTGAAAGAGTTTATAGATTGGATGCATTTGGAGCCCCA GTCCATGGTTTGGCTCCCAGTGTTACATAGGGTAGCTGCTGCAGAGACTGCCAAACATCAGGCCAAAT GCAACATCTGTAAAGAATGTCCAATTGTGGGCTTCAGGTATAGATCTCTTAAGCATTTTAACTATGAT GTCTGCCAGAGTTGTTTCTTTAGTGGTAGAACTGCAAAAGGTCACAAATTACATTACCCAATGGTGGA GT AT TGT AT ACCT ACAACAT CAGGTGAAGAT GT CAGAGAT T TCACAAAGGT ACT T AAGAACAAGT TCA GGTCAAAGAAGTACTTTGCTAAACACCCAAGACTGGGTTACCTGCCTGTACAGACTGTTCTTGAGGGT GACAAC T T AGAAAC TCAGGCTATGTGA

[0187] G12 ( SEQ ID NO : 109 )ATGGCTAAGTATGGGGAACATGAGGCCAGTCCAGACAATGGGCAGAATGAATTCTCTGATATCATTAA GTCCAGATCTGATGAACACAATGATGTGCAGAAGAAAACCTTTACCAAATGGATAAATGCTAGATTTT CAAAGAGTGGGAAACCACCCATCAATGACATGTTCACTGACCTCAAAGATGGGAGAAAGCTACTAGAT CTTCTAGAAGGCCTCACTGGAACATCACTGCCCAAGGAAAGGGGTTCCACAAGGGTACATGCCTTAAA TAATGTCAACAGAGTGCTGCAGGTTTTACATCAGAACAATGTGGAACTGGTGAATATAGGTGGCACTG ACATTGTGGATGGCAATCACAAACTGACTTTGGGGTTACTTTGGTCTATCATTTTGCACTGGCAGGTG AAAGATGTCATGAAGGATGTGATGTCAGACCTGCAGCAGACAAACTCAGAAAAGATCCTGCTCAGCTG GGTGAGACAGACCACTAGGCCTTACAGTCAAGTCAATGTCCTCAACTTCACCACCAGCTGGACAGATG GCCTGGCCTTTAATGCTGTCCTCCACAGACATAAACCTGATCTCTTCAGCTGGGATAAAGTTGTCAAA ATGTCACCAATTGAGAGGCTTGAACATGCTTTCAGCAAGGCCCAAACTTATTTGGGAATTGAAAAGCT GTTAGATCCTGAAGATGTGGCAGTGCAGCTTCCAGACAAGAAATCCATAATTATGTATTTAACATCTT TGTTTGAGGTGCTACCTCAGCAAGTCACCATTGATGCCATCAGAGAGGTAGAGACTCTCCCAAGGAAA T ATAAAAAAGAAT GT GAGGAAGAGGCAAT TAAT ATACAGT CCACAGCCCCT GAGGAGGAGCAT GAGAG TCCCAGAGCTGAGACTCCCAGCACAGTCACAGAGGTGGACATGGATCTGGACAGTTATCAGATTGCTC TGGAGGAAGTGCTGACCTGGTTGCTTTCAGCTGAAGACACTTTCCAGGAGCAGGATGACATTTCTGAT GATGTGGAGGAAGTCAAAGACCAGTTTGCAACTCATGAGGCTTTTATGATGGAACTGACTGCTCACCA GAGCAGTGTGGGCAGTGTGCTGCAGGCAGGCAACCAACTGATAACCCAAGGAACTCTGAGTGATGAAG AAGAATTTGAGATTCAGGAACAGATGACTCTGCTGAATGCCAGATGGGAGGCTCTTAGGGTGGAGAGT ATGGACAGGCAGTCAAGACTGCATGATGTGCTGATGGAACTGCAGAAGAAGCAACTGCAGCAGCTCTCAGCCTGGTTAACACTCACTGAGGAGAGGATTCAGAAGATGGAAACCTGCCCTCTGGATGATGATGTCA AATCTCTACAAAAGCTGCTAGAAGAACATAAAAGTTTGCAATCTGATCTTGAGGCTGAACAGGTGAAA GTAAATTCACTAACTCACATGGTGGTGATTGTTGATGAAAACAGTGGAGAGAGTGCAACAGCTATCCT AGAAGACCAGTTACAGAAACTTGGTGAGAGGTGGACTGCAGTCTGCAGATGGACAGAAGAAAGATGGA ATAGGTTACAAGAAATCAATATATTGTGGCAGGAATTATTGGAAGAACAGTGCTTGTTGAAAGCTTGG TTAACTGAGAAAGAAGAGGCCTTAAATAAAGTCCAGACAAGCAACTTCAAAGACCAAAAGGAACTAAG TGTGTCTGTTAGGAGGCTGGCTATTTTGAAGGAAGACATGGAAATGAAGAGACAAACCTTGGATCAGC TGAGTGAGATTGGGCAGGATGTGGGTCAATTACTTGATAATTCCAAGGCCTCTAAGAAGATCAACAGT GACTCTGAAGAACTGACTCAAAGATGGGATTCTCTTGTTCAGAGATTGGAAGATTCCTCCAACCAGGT GACTCAGGCAGTGGCCAAGTTAGGGATGTCTCAGATTCCTCAGAAGGACCTTTTGGAGACAGTTAGAG TAAGAGAACAAGCCATTACTAAAAAATCCAAGCAGGAACTGCCTCCTCCTCCTCCCCCAAAGAAGAGA CAGATCCATGTGGATTTGGAAAAACTCAGGGACCTGCAGGGAGCCATGGATGATCTGGATGCTGACAT GAAGGAGGCTGAAAGTGTGAGAAATGGATGGAAGCCAGTGGGAGACTTACTCATTGACTCACTGCAGG ATCACATTGAGAAAATCATGGCATTTAGGGAAGAAATTGCACCCATCAACTTTAAAGTTAAAACTGTG AATGATTTATCTAGCCAGCTGAGTCCCCTTGACCTGCATCCAAGCCTAAAGATGTCTAGACAGCTAGA TGATCTTAATATGAGGTGGAAACTTTTACAGGTTTCTGTTGATGACAGACTTAAACAGCTTCAGGAAG CCCACAGAGATTTTGGGCCATCCTCTCAGCATTTTCTCTCTACTTCTGTGCAGCTGCCCTGGCAAAGA T C CAT T T C AC AT AAT AAAGT GO C AT AT T AC AT C AAC C AT C AAAC ACAGAC C AC AT GT T GGGAC C ATC C TAAAATGACTGAACTCTTTCAAAGCCTTGCAGACCTGAATAATGTAAGATTTTCAGCCTACAGGACAG CTATCAAAATCAGGAGACTACAAAAAGCACTATGTTTGGACCTCTTAGAGTTGAGTACTACAAATGAA ATTTTCAAACAGCACAAGTTGAACCAAAATGACCAGCTCCTCAGTGTGCCAGATGTAATCAACTGTCT GACAACAACCTATGATGGACTTGAGCAAATGCATAAGGACCTGGTCAATGTGCCACTCTGTGTGGATA TGTGTCTCAATTGGTTGCTCAATGTGTATGACACAGGTAGGACAGGAAAAATTAGGGTGCAGAGTCTG AAGATAGGATTAATGTCTCTCAGCAAAGGTCTCTTGGAAGAAAAATACAGGTATCTCTTTAAGGAAGT GGCAGGTCCAACAGAAATGTGTGATCAGAGGCAGCTGGGCCTGTTACTTCATGATGCCATCCAGATCC CTAGGCAGCTGGGTGAGGTAGCAGCCTTTGGTGGCTCAAATATTGAGCCCTCTGTTAGAAGCTGCTTC CAACAGAATAACAATAAACCTGAAATAAGTGTGAAAGAGTTTATAGATTGGATGCATTTGGAGCCCCA GTCCATGGTTTGGCTCCCAGTTTTACATAGAGTTGCAGCAGCTGAGACTGCCAAACATCAGGCCAAAT GCAACATCTGTAAAGAATGTCCAATTGTAGGCTTCAGGTATAGGTCTCTTAAGCATTTTAACTATGAT GTGTGCCAGAGTTGTTTCTTTTCTGGCAGAACAGCTAAAGGTCACAAATTACATTACCCAATGGTGGA ATATTGTATACCTACAACATCTGGGGAAGATGTTAGAGACTTCACAAAGGTACTTAAGAACAAGTTCA GGAGTAAGAAGTACTTTGCCAAACACCCCAGATTGGGTTACCTGCCAGTCCAGACAGTTCTGGAAGGT GACAAC T T AGAGAC T C AGGC C AT GT GA

[0188] G13 ( SEQ ID NO : 110 )ATGGCTAAGTATGGAGAACATGAAGCTAGTCCTGACAATGGGCAGAATGAGTTCAGTGACATCATTAA GTCCAGATCTGATGAGCACAATGATGTCCAGAAGAAAACCTTTACCAAATGGATAAATGCCAGGTTTT CAAAGAGTGGGAAACCACCTATCAATGATATGTTCACAGACCTCAAAGATGGAAGGAAGCTACTGGAT CTTCTAGAAGGCCTCACTGGGACATCACTGCCTAAGGAAAGGGGTTCCACAAGGGTACATGCTTTAAA TAATGTCAACAGGGTGCTGCAGGTTTTACATCAGAACAATGTGGAACTGGTGAATATTGGGGGTACAG ACATTGTGGATGGCAATCACAAACTGACTTTGGGGTTACTTTGGTCAATCATTTTGCACTGGCAGGTG AAAGATGTGATGAAGGATGTTATGTCTGACCTGCAGCAGACTAACAGTGAAAAGATCCTGCTCAGCTG GGTGAGGCAGACCACTAGGCCCTACTCCCAAGTCAATGTTCTCAACTTCACCACCTCTTGGACAGATG GCTTAGCCTTTAATGCTGTGCTCCACAGGCATAAACCAGACCTCTTCAGCTGGGATAAAGTTGTCAAA ATGTCACCAATTGAGAGACTTGAACATGCCTTCAGCAAGGCTCAAACCTATTTGGGAATTGAAAAGCT GTTAGATCCAGAAGATGTGGCTGTTCAGCTTCCAGACAAGAAATCCATAATTATGTATTTAACATCTT TGTTTGAAGTGCTACCTCAGCAAGTCACTATAGATGCTATCAGGGAGGTAGAGACACTCCCTAGGAAA T ATAAAAAAGAAT GT GAAGAAGAGGCAAT T AAT ATACAGAGTACAGCCCCAGAAGAGGAGCAT GAGAG TCCCAGGGCTGAGACTCCCAGCACTGTCACAGAGGTAGACATGGATCTGGACTCTTATCAGATTGCAC TGGAGGAAGTGCTGACCTGGTTGCTTTCTGCAGAGGACACTTTCCAGGAGCAGGATGACATTTCTGAT GATGTTGAGGAAGTCAAAGACCAGTTTGCTACCCATGAGGCTTTTATGATGGAACTGACTGCTCACCA GAGCAGTGTGGGCAGTGTGCTGCAGGCAGGCAACCAACTGATAACCCAAGGAACTCTGTCAGATGAAG AAGAATTTGAGATTCAGGAACAGATGACTCTGCTGAATGCTAGATGGGAGGCTCTTAGGGTGGAGAGT ATGGACAGACAGAGTAGGCTGCATGATGTCCTGATGGAACTGCAGAAGAAGCAACTGCAGCAGCTCAGTGCTTGGTTAACACTCACAGAGGAGAGAATTCAGAAGATGGAAACCTGCCCCCTGGATGATGATGTCA AATCTCTACAAAAGCTGCTAGAAGAACATAAAAGTTTGCAATCAGATCTTGAGGCTGAGCAGGTGAAA GTAAATTCACTAACTCACATGGTGGTCATTGTTGATGAAAACAGTGGTGAGAGTGCTACAGCCATCCT AGAAGACCAGTTACAGAAACTTGGAGAGAGGTGGACTGCAGTATGCAGATGGACAGAAGAAAGATGGA ATAGGTTACAAGAAATCAATATATTGTGGCAGGAATTATTGGAAGAACAGTGCTTGTTGAAAGCTTGG T T AACAGAAAAAGAAGAGGC C T TAAAT AAAGT C C AGAC CAGCAAC T T C AAAGAC C AAAAGGAAC T AAG TGTGAGTGTGAGGAGGCTGGCTATTTTGAAGGAAGACATGGAAATGAAGAGGCAAACATTGGATCAGC TGAGTGAAATTGGCCAGGATGTGGGACAATTACTAGATAATTCCAAGGCCTCTAAGAAGATCAACTCT GACTCTGAGGAACTGACTCAAAGATGGGATTCTTTGGTTCAGAGACTTGAAGATTCCTCCAACCAGGT GACTCAGGCTGTTGCTAAGCTGGGGATGTCACAGATTCCTCAGAAGGACCTTTTGGAGACTGTAAGAG TAAGAGAACAAGCAATTACCAAAAAATCAAAGCAGGAACTGCCTCCTCCTCCTCCCCCAAAGAAGAGA CAGATCCATGTGGATTTAGAGAAACTCAGAGACCTGCAGGGGGCTATGGATGACCTGGATGCAGATAT GAAGGAGGCTGAGAGTGTGAGGAATGGCTGGAAGCCTGTGGGAGACTTACTCATTGATAGCCTGCAGG ATCACATTGAGAAAATCATGGCCTTTAGAGAAGAAATTGCCCCTATCAACTTTAAAGTTAAAACAGTC AATGACTTATCCAGCCAGCTGTCCCCACTTGACCTGCATCCATCCCTAAAGATGTCTAGACAGCTAGA TGACCTTAATATGAGGTGGAAACTTTTACAGGTTAGTGTGGATGATAGGCTTAAACAGCTTCAGGAAG CCCACAGAGATTTTGGACCATCCTCTCAGCATTTTCTCTCTACTAGTGTTCAGCTGCCATGGCAAAGA T C CAT T T C AC AT AAT AAAGT GO C AT AT T AC AT C AAC C AT C AAAC ACAGAC AAC C T GT T GGGAC C ATC C TAAAATGACAGAACTCTTTCAATCCCTTGCTGATCTGAATAATGTGAGGTTTTCAGCTTACAGAACTG CCATCAAAATCAGAAGACTACAAAAAGCACTATGTCTTGATCTCTTAGAGTTGAGTACCACAAATGAA ATTTTCAAACAGCACAAGTTGAACCAAAATGACCAGCTCCTCAGTGTTCCAGATGTCATCAACTGTCT GACCACAACATATGATGGCTTGGAGCAAATGCATAAGGACCTGGTCAATGTGCCCCTCTGTGTGGATA TGTGTCTCAATTGGTTGCTCAATGTCTATGACACTGGTAGGACAGGCAAAATTAGAGTGCAGAGTCTG AAGATTGGTTTAATGTCTCTCAGTAAAGGTCTCTTGGAAGAAAAATACAGATATCTCTTTAAGGAAGT GGCTGGGCCCACTGAAATGTGTGACCAGAGGCAGCTGGGCCTGTTACTTCATGATGCCATCCAGATCC CAAGGCAGCTGGGGGAAGTAGCAGCCTTTGGAGGCAGCAATATTGAACCTTCTGTTAGAAGCTGCTTC CAACAGAATAACAATAAACCAGAGATAAGTGTCAAAGAGTTTATTGACTGGATGCATCTGGAACCTCA GTCCATGGTTTGGCTCCCAGTGTTACATAGGGTGGCTGCTGCAGAAACTGCCAAACATCAGGCCAAAT GCAACATCTGTAAAGAATGTCCAATTGTGGGTTTCAGGTATAGGTCCCTTAAGCATTTTAACTATGAT GTCTGCCAGAGTTGTTTCTTTAGTGGGAGAACAGCAAAAGGTCACAAATTACATTACCCAATGGTGGA GTATTGTATACCTACAACATCTGGGGAGGATGTAAGAGACTTCACAAAGGTACTTAAGAACAAGTTCA GGTCAAAGAAGTACTTTGCTAAACACCCTAGACTGGGTTACCTGCCTGTCCAGACTGTGCTTGAGGGT GACAAC T T AGAGAC T C AGGC C AT GT GA

[0189] G1 ( SEQ ID NO : 111 )ATGGCTAAGTATGGAGAACATGAGGCCAGTCCAGACAATGGGCAGAATGAGTTCAGTGACATCATTAA GTCCAGAAGTGATGAACACAATGATGTACAGAAGAAAACCTTTACCAAATGGATAAATGCTAGATTTT CAAAGTCTGGGAAACCACCTATCAATGATATGTTCACAGACCTCAAAGATGGCAGAAAGCTATTGGAC CTTCTAGAAGGCCTCACTGGCACATCACTGCCCAAGGAAAGAGGTTCCACAAGGGTACATGCATTAAA TAATGTTAACAGGGTGCTGCAGGTTTTACATCAGAACAATGTGGAACTGGTGAATATAGGTGGAACTG ATATTGTGGATGGCAATCACAAACTGACTTTGGGGTTACTTTGGAGTATCATTTTGCACTGGCAGGTG AAAGATGTTATGAAGGATGTGATGTCTGACCTGCAGCAGACCAACTCAGAGAAGATCCTGCTCAGCTG GGTGAGGCAGACCACTAGGCCATACTCCCAAGTCAATGTGCTCAACTTCACCACCTCCTGGACAGATG GCCTTGCCTTTAATGCTGTCCTCCACAGACATAAACCTGATCTCTTCAGCTGGGATAAAGTTGTCAAA ATGTCACCAATTGAGAGGCTTGAACATGCCTTCAGCAAGGCCCAAACTTATTTGGGAATTGAAAAGCT GTTAGATCCTGAAGATGTGGCTGTGCAGCTTCCAGACAAGAAATCCATAATTATGTATTTAACATCTT TGTTTGAGGTGCTACCTCAGCAAGTCACAATTGATGCTATCAGAGAGGTAGAGACCCTCCCCAGGAAA TATAAAAAAGAATGTGAGGAAGAGGCAATTAATATACAGAGCACAGCTCCAGAGGAGGAGCATGAGAG TCCCAGGGCAGAGACTCCCAGCACTGTTACAGAGGTTGACATGGATCTGGACTCATATCAGATTGCCC TGGAGGAAGTGCTGACCTGGTTGCTTAGTGCAGAGGACACTTTCCAGGAGCAGGATGACATTAGTGAT GATGTGGAAGAAGTCAAAGACCAGTTTGCCACCCATGAGGCTTTTATGATGGAACTGACTGCCCACCA GAGCAGTGTGGGCTCTGTTCTGCAGGCTGGCAACCAACTGATAACCCAAGGAACTCTGTCAGATGAAG AAGAAT T T GAAAT T CAGGAACAGATGACACT GCT GAAT GCAAGAT GGGAGGCT CT T AGGGT GGAGAGT ATGGACAGACAGTCTAGGCTGCATGATGTGCTGATGGAACTGCAGAAGAAGCAACTGCAGCAGCTCTCAGCCTGGTTAACACTCACAGAGGAGAGAATTCAGAAGATGGAAACATGCCCACTGGATGATGATGTGA AATCTCTACAAAAGCTGCTAGAAGAACATAAAAGTTTGCAATCAGATCTTGAGGCTGAGCAGGTGAAA GTAAATTCACTAACTCACATGGTGGTTATTGTGGATGAAAACTCAGGTGAATCAGCAACAGCTATCCT AGAAGACCAGTTACAGAAACTTGGAGAGAGGTGGACAGCTGTATGCAGGTGGACTGAAGAAAGGTGGA AT AGAT T ACAAGAAAT CAAT AT AT TGT GGCAGGAAT T ATT GGAAGAACAGT GCT T GT T GAAAGCT TGG TTAACTGAAAAAGAAGAGGCCTTAAATAAAGTCCAGACAAGCAACTTCAAAGACCAAAAGGAACTAAG TGTGAGTGTTAGGAGGCTGGCTATTTTGAAGGAAGACATGGAAATGAAGAGGCAAACATTGGATCAGC TGAGTGAGATTGGCCAGGATGTGGGACAATTACTTGACAATTCCAAGGCATCTAAGAAGATCAACTCT GACAGTGAGGAACTGACTCAAAGATGGGATTCTTTGGTGCAGAGACTAGAGGATTCCTCCAACCAGGT GACTCAGGCTGTGGCAAAGCTGGGGATGTCTCAGATTCCTCAGAAGGACCTTCTGGAGACTGTTAGAG TAAGAGAACAAGCTATTACCAAAAAATCTAAGCAGGAACTGCCTCCTCCTCCACCCCCAAAGAAGAGG CAGATCCATGTGGATTTGGAAAAACTCAGAGACCTGCAGGGGGCTATGGATGACCTGGATGCAGACAT GAAGGAGGCAGAGAGTGTGAGAAATGGCTGGAAGCCAGTGGGAGACTTACTCATTGATTCCCTGCAGG ATCACATTGAAAAAATCATGGCATTTAGGGAAGAAATAGCCCCAATCAACTTTAAAGTTAAAACAGTG AATGACTTAAGCTCTCAGCTGTCACCCCTTGACCTGCATCCATCACTAAAGATGTCTAGGCAGCTAGA TGATCTTAATATGAGGTGGAAACTTTTACAGGTTAGTGTAGATGATAGGCTTAAACAGCTTCAGGAAG CCCACAGAGATTTTGGTCCATCCTCTCAGCATTTTCTCTCTACCTCTGTGCAGCTGCCTTGGCAAAGA T C CAT T T C AC ATAAT AAAGT GO C AT AT T AC AT C AAC C AT C AAAC ACAGAC T AC AT GT T GGGAC C ATC C TAAAATGACAGAACTCTTTCAATCCCTTGCAGACCTGAATAATGTGAGGTTTTCAGCCTACAGAACTG CCATCAAAATCAGAAGACTACAAAAAGCACTATGTCTGGATCTCTTAGAGTTGAGTACCACCAATGAA ATTTTCAAACAGCACAAGTTGAACCAAAATGACCAGCTCCTCAGTGTCCCAGATGTCATCAACTGTCT GACTACAACTTATGATGGCCTTGAACAAATGCATAAGGACCTGGTCAATGTGCCACTCTGTGTGGACA TGTGTCTCAATTGGTTGCTCAATGTTTATGATACAGGTAGGACAGGAAAAATTAGGGTGCAGAGTCTG AAGATTGGATTAATGTCTCTCAGTAAAGGTCTCTTGGAAGAAAAATACAGATATCTCTTTAAGGAAGT TGCTGGGCCTACTGAAATGTGTGATCAGAGGCAGCTGGGCCTGTTACTTCATGATGCCATCCAGATCC CCAGGCAGCTGGGAGAGGTAGCAGCTTTTGGAGGCAGCAATATAGAGCCAAGTGTCAGGAGCTGCTTC CAACAGAATAACAATAAACCTGAAATATCAGTGAAAGAGTTTATAGATTGGATGCATTTGGAACCTCA GTCCATGGTTTGGCTCCCAGTTTTACATAGGGTGGCTGCAGCAGAGACTGCAAAACATCAGGCCAAAT GCAACATCTGTAAAGAATGTCCAATAGTAGGCTTCAGGTATAGGTCACTTAAGCATTTTAACTATGAT GTCTGCCAGAGTTGTTTCTTTAGTGGTAGAACTGCTAAAGGTCACAAATTACATTACCCAATGGTGGA ATATTGTATACCTACAACATCAGGTGAGGATGTGAGGGACTTCACAAAGGTACTTAAGAACAAGTTCA GGTCAAAGAAGTACTTTGCTAAACACCCAAGATTGGGTTACCTGCCTGTGCAGACAGTGTTAGAAGGT GACAAC T T AGAGAC T C AGGC C AT GT GA

[0190] Prior art construct- [ [US7771993B2 ] ] ( SEQ ID NO : 112 )ATGGCCAAGTATGGAGAACATGAAGCCAGTCCTGACAATGGGCAGAACGAATTCAGTGATATCATTAA GTCCAGATCTGATGAACACAATGACGTACAGAAGAAAACCTTTACCAAATGGATAAATGCTCGATTTT CAAAGAGT GGGAAACCACCCAT CAATGAT AT GT T CACAGACCT CAAAGAT GGAAGGAAGCT AT T GGAT CTTCTAGAAGGCCTCACAGGAACATCACTGCCAAAGGAACGTGGTTCCACAAGGGTACATGCCTTAAA TAACGTCAACAGAGTGCTGCAGGTTTTACATCAGAACAATGTGGAATTAGTGAATATAGGGGGAACTG ACATTGTGGATGGAAATCACAAACTGACTTTGGGGTTACTTTGGAGCATCATTTTGCACTGGCAGGTG AAAGATGTCATGAAGGATGTCATGTCGGACCTGCAGCAGACGAACAGTGAGAAGATCCTGCTCAGCTG GGTGCGTCAGACCACCAGGCCCTACAGCCAAGTCAACGTCCTCAACTTCACCACCAGCTGGACAGATG GACTCGCCTTTAATGCTGTCCTCCACCGACATAAACCTGATCTCTTCAGCTGGGATAAAGTTGTCAAA ATGTCACCAATTGAGAGACTTGAACATGCCTTCAGCAAGGCTCAAACTTATTTGGGAATTGAAAAGCT GTTAGATCCTGAAGATGTTGCCGTTCGGCTTCCTGACAAGAAATCCATAATTATGTATTTAACATCTT TGTTTGAGGTGCTACCTCAGCAAGTCACCATAGACGCCATCCGTGAGGTAGAGACACTCCCAAGGAAA TATAAAAAAGAATGTGAAGAAGAGGCAATTAATATACAGAGTACAGCGCCTGAGGAGGAGCATGAGAG TCCCCGAGCTGAAACTCCCAGCACTGTCACTGAGGTCGACATGGATCTGGACAGCTATCAGATTGCGT TGGAGGAAGTGCTGACCTGGTTGCTTTCTGCTGAGGACACTTTCCAGGAGCAGGATGATATTTCTGAT GATGTTGAAGAAGTCAAAGACCAGTTTGCAACCCATGAAGCTTTTATGATGGAACTGACTGCACACCA GAGCAGTGTGGGCAGCGTCCTGCAGGCAGGCAACCAACTGATAACACAAGGAACTCTGTCAGACGAAG AAGAATTTGAGATTCAGGAACAGATGACCCTGCTGAATGCTAGATGGGAGGCTCTTAGGGTGGAGAGT ATGGACAGACAGTCCCGGCTGCACGATGTGCTGATGGAACTGCAGAAGAAGCAACTGCAGCAGCTCTCCGCCTGGTTAACACTCACAGAGGAGCGCATTCAGAAGATGGAAACTTGCCCCCTGGATGATGATGTAA AATCTCTACAAAAGCTGCTAGAAGAACATAAAAGTTTGCAAAGTGATCTTGAGGCTGAACAGGTGAAA GTAAATTCACTAACTCACATGGTGGTCATTGTTGATGAAAACAGTGGTGAGAGCGCTACAGCTATCCT AGAAGACCAGTTACAGAAACTTGGTGAGCGCTGGACAGCAGTATGCCGTTGGACTGAAGAACGCTGGA ATAGGTTACAAGAAATCAATATATTGTGGCAGGAATTATTGGAAGAACAGTGCTTGTTGAAAGCTTGG TTAACCGAAAAAGAAGAGGCTTTAAATAAAGTCCAGACAAGCAACTTCAAAGACCAAAAGGAACTAAG TGTCAGTGTTCGACGTCTGGCTATTTTGAAGGAAGACATGGAAATGAAGCGTCAAACATTGGATCAGC TGAGTGAGATTGGCCAGGATGTGGGACAATTACTTGATAATTCCAAGGCATCTAAGAAGATCAACAGT GACTCAGAGGAACTGACTCAAAGATGGGATTCTTTGGTTCAGAGACTAGAAGATTCCTCCAACCAGGT GACTCAGGCTGTAGCAAAGCTGGGGATGTCTCAGATTCCTCAGAAGGACCTTTTGGAGACTGTTCGTG TAAGAGAACAAGCAATTACAAAAAAATCTAAGCAGGAACTGCCTCCTCCTCCTCCCCCAAAGAAGAGA CAGATCCATGTGGATTTGGAGAAACTCAGAGACCTGCAGGGAGCTATGGATGACCTGGACGCTGACAT GAAGGAGGCAGAGTCCGTGCGGAATGGCTGGAAGCCCGTGGGAGACTTACTCATTGACTCGCTGCAGG ATCACATTGAAAAAATCATGGCATTTAGAGAAGAAATTGCACCAATCAACTTTAAAGTTAAAACGGTG AATGATTTATCCAGTCAGCTGTCTCCACTTGACCTGCATCCCTCTCTAAAGATGTCTCGCCAGCTAGA TGACCTTAATATGCGATGGAAACTTTTACAGGTTTCTGTGGATGATCGCCTTAAACAGCTTCAGGAAG CCCACAGAGATTTTGGACCATCCTCTCAGCATTTTCTCTCTACGTCAGTCCAGCTGCCGTGGCAAAGA T C CAT T T C AC AT AAT AAAGT GO C C T AT T AC AT C AAC C AT C AAAC ACAGAC C AC C T GT T GGGAC C ATC C TAAAATGACCGAACTCTTTCAATCCCTTGCTGACCTGAATAATGTACGTTTTTCTGCCTACCGTACAG CAAT CAAAAT CCGAAGACTACAAAAAGCACT AT GTT T GGAT CT CT TAGAGT TGAGT ACAACAAAT GAA ATTTTCAAACAGCACAAGTTGAACCAAAATGACCAGCTCCTCAGTGTTCCAGATGTCATCAACTGTCT GACAACAACTTATGATGGACTTGAGCAAATGCATAAGGACCTGGTCAACGTTCCACTCTGTGTTGATA TGTGTCTCAATTGGTTGCTCAATGTCTATGACACGGGTCGAACTGGAAAAATTAGAGTGCAGAGTCTG AAGATTGGATTAATGTCTCTCTCCAAAGGTCTCTTGGAAGAAAAATACAGATATCTCTTTAAGGAAGT TGCGGGGCCGACAGAAATGTGTGACCAGAGGCAGCTGGGCCTGTTACTTCATGATGCCATCCAGATCC CCCGGCAGCTAGGTGAAGTAGCAGCTTTTGGAGGCAGTAATATTGAGCCTAGTGTTCGCAGCTGCTTC CAACAGAAT AACAAT AAACCAGAAATAAGT GTGAAAGAGT T TAT AGAT TGGAT GCAT T TGGAACCACA GTCCATGGTTTGGCTCCCAGTTTTACATCGAGTGGCAGCAGCGGAGACTGCAAAACATCAGGCCAAAT GCAACATCTGTAAAGAATGTCCAATTGTCGGGTTCAGGTATAGAAGCCTTAAGCATTTTAACTATGAT GTCTGCCAGAGTTGTTTCTTTTCGGGTCGAACAGCAAAAGGTCACAAATTACATTACCCAATGGTGGA ATATTGTATACCTACAACATCTGGGGAAGATGTACGAGACTTCACAAAGGTACTTAAGAACAAGTTCA GGTCGAAGAAGTACTTTGCCAAACACCCTCGACTTGGTTACCTGCCTGTCCAGACAGTTCTTGAAGGT GACAACTTAGAGACTTGA

[0191] wt_human ( SEQ I D NO : 113 )ATGGCCAAGTATGGAGAACATGAAGCCAGTCCTGACAATGGGCAGAACGAATTCAGTGATATCATTAA GTCCAGATCTGATGAACACAATGACGTACAGAAGAAAACCTTTACCAAATGGATAAATGCTCGATTTT CAAAGAGT GGGAAACCACCCAT CAATGAT AT GT T CACAGACCT CAAAGAT GGAAGGAAGCT AT TGGAT CTTCTAGAAGGCCTCACAGGAACATCACTGCCAAAGGAACGTGGTTCCACAAGGGTACATGCCTTAAA TAACGTCAACAGAGTGCTGCAGGTTTTACATCAGAACAATGTGGAATTAGTGAATATAGGGGGAACTG ACATTGTGGATGGAAATCACAAACTGACTTTGGGGTTACTTTGGAGCATCATTTTGCACTGGCAGGTG AAAGATGTCATGAAGGATGTCATGTCGGACCTGCAGCAGACGAACAGTGAGAAGATCCTGCTCAGCTG GGTGCGTCAGACCACCAGGCCCTACAGCCAAGTCAACGTCCTCAACTTCACCACCAGCTGGACAGATG GACTCGCCTTTAATGCTGTCCTCCACCGACATAAACCTGATCTCTTCAGCTGGGATAAAGTTGTCAAA ATGTCACCAATTGAGAGACTTGAACATGCCTTCAGCAAGGCTCAAACTTATTTGGGAATTGAAAAGCT GTTAGATCCTGAAGATGTTGCCGTTCAGCTTCCTGACAAGAAATCCATAATTATGTATTTAACATCTT TGTTTGAGGTGCTACCTCAGCAAGTCACCATAGACGCCATCCGTGAGGTAGAGACACTCCCAAGGAAA TATAAAAAAGAATGTGAAGAAGAGGCAATTAATATACAGAGTACAGCGCCTGAGGAGGAGCATGAGAG TCCCCGAGCTGAAACTCCCAGCACTGTCACTGAGGTTGACATGGATCTGGACAGCTATCAGATTGCGT TGGAGGAAGTGCTGACCTGGTTGCTTTCTGCTGAGGACACTTTCCAGGAGCAGGATGATATTTCTGAT GATGTTGAAGAAGTCAAAGACCAGTTTGCAACCCATGAAGCTTTTATGATGGAACTGACTGCACACCA GAGCAGTGTGGGCAGCGTCCTGCAGGCAGGCAACCAACTGATAACACAAGGAACTCTGTCAGACGAAG AAGAATTTGAGATTCAGGAACAGATGACCCTGCTGAATGCTAGATGGGAGGCTCTTAGGGTGGAGAGT ATGGACAGACAGTCCCGGCTGCACGATGTGCTGATGGAACTGCAGAAGAAGCAACTGCAGCAGCTCTCCGCCTGGTTAACACTCACAGAGGAGCGCATTCAGAAGATGGAAACTTGCCCCCTGGATGATGATGTAA AATCTCTACAAAAGCTGCTAGAAGAACATAAAAGTTTGCAAAGTGATCTTGAGGCTGAACAGGTGAAA GTAAATTCACTAACTCACATGGTGGTCATTGTTGATGAAAACAGTGGTGAGAGTGCTACAGCTATCCT AGAAGACCAGTTACAGAAACTTGGTGAGCGCTGGACAGCAGTATGCCGTTGGACTGAAGAACGCTGGA ATAGGTTACAAGAAATCAATATATTGTGGCAGGAATTATTGGAAGAACAGTGCTTGTTGAAAGCTTGG TTAACCGAAAAAGAAGAGGCTTTAAATAAAGTCCAGACAAGCAACTTCAAAGACCAAAAGGAACTAAG TGTCAGTGTTCGACGTCTGGCTATTTTGAAGGAAGACATGGAAATGAAGCGTCAAACATTGGATCAGC TGAGTGAGATTGGCCAGGATGTGGGACAATTACTTGATAATTCCAAGGCATCTAAGAAGATCAACAGT GACTCAGAGGAACTGACTCAAAGATGGGATTCTTTGGTTCAGAGACTAGAAGATTCCTCCAACCAGGT GACTCAGGCTGTAGCAAAGCTGGGGATGTCTCAGATTCCTCAGAAGGACCTTTTGGAGACTGTTCGTG TAAGAGAACAAGCAATTACAAAAAAATCTAAGCAGGAACTGCCTCCTCCTCCTCCCCCAAAGAAGAGA CAGATCCATGTGGATTTGGAGAAACTCAGAGACCTGCAGGGAGCTATGGATGACCTGGACGCTGACAT GAAGGAGGCAGAGTCCGTGCGGAATGGCTGGAAGCCCGTGGGAGACTTACTCATTGACTCGCTGCAGG ATCACATTGAAAAAATCATGGCATTTAGAGAAGAAATTGCACCAATCAACTTTAAAGTTAAAACGGTG AATGATTTATCCAGTCAGCTGTCTCCACTTGACCTGCATCCCTCTCTAAAGATGTCTCGCCAGCTAGA TGACCTTAATATGCGATGGAAACTTTTACAGGTTTCTGTGGATGATCGCCTTAAACAGCTTCAGGAAG CCCACAGAGATTTTGGACCATCCTCTCAGCATTTTCTCTCTACGTCAGTCCAGCTGCCGTGGCAAAGA T C CAT T T C AC AT AAT AAAGT GO C C T AT T AC AT C AAC C AT C AAAC ACAGAC C AC C T GT T GGGAC C ATC C TAAAATGACCGAACTCTTTCAATCCCTTGCTGACCTGAATAATGTACGTTTTTCTGCCTACCGTACAG CAAT CAAAAT CCGAAGACTACAAAAAGCACT AT GTT T GGAT CT CT TAGAGT TGAGT ACAACAAAT GAA ATTTTCAAACAGCACAAGTTGAACCAAAATGACCAGCTCCTCAGTGTTCCAGATGTCATCAACTGTCT GACAACAACTTATGATGGACTTGAGCAAATGCATAAGGACCTGGTCAACGTTCCACTCTGTGTTGATA TGTGTCTCAATTGGTTGCTCAATGTCTATGACACGGGTCGAACTGGAAAAATTAGAGTGCAGAGTCTG AAGATTGGATTAATGTCTCTCTCCAAAGGTCTCTTGGAAGAAAAATACAGATATCTCTTTAAGGAAGT TGCAGGGCCAACAGAAATGTGTGACCAGAGGCAGCTGGGCCTGTTACTTCATGATGCCATCCAGATCC CCCGGCAGCTAGGTGAAGTAGCAGCTTTTGGAGGCAGTAATATTGAGCCTAGTGTTCGCAGCTGCTTC CAACAGAAT AACAAT AAACCAGAAATAAGT GTGAAAGAGT T TAT AGAT TGGAT GCAT T TGGAACCACA GTCCATGGTTTGGCTCCCAGTTTTACATCGAGTGGCAGCAGCGGAGACTGCAAAACATCAGGCCAAAT GCAACATCTGTAAAGAATGTCCAATTGTCGGGTTCAGGTATAGAAGCCTTAAGCATTTTAACTATGAT GTCTGCCAGAGTTGTTTCTTTTCGGGTCGAACAGCAAAAGGTCACAAATTACATTACCCAATGGTGGA ATATTGTATACCTACAACATCTGGGGAAGATGTACGAGACTTCACAAAGGTACTTAAGAACAAGTTCA GGTCGAAGAAGTACTTTGCCAAACACCCTCGACTTGGTTACCTGCCTGTCCAGACAGTTCTTGAAGGT GACAAC T T AGAGAC T C AGGC AAT GT GANucleic Acids

[0192] In one aspect of any of the embodiments, described herein is a nucleic acid encoding a polypeptide described herein.

[0193] In some embodiments of any of the aspects, the nucleic acid comprises a sequence with at least 70% sequence identity to one of SEQ ID NOs: 85-87. In some embodiments of any of the aspects, the nucleic acid comprises a sequence with at least 75% sequence identity to one of SEQ ID NOs: 85-87. In some embodiments of any of the aspects, the nucleic acid comprises a sequence with at least 80% sequence identity to one of SEQ ID NOs: 85-87. In some embodiments of any of the aspects, the nucleic acid comprises a sequence with at least 85% sequence identity to one of SEQ ID NOs: 85-87. In some embodiments of any of the aspects, the nucleic acid comprises a sequence with at least 90% sequence identity to one of SEQ ID NOs: 85-87. In some embodiments of any of the aspects, the nucleic acid comprises a sequence with at least 95% sequence identity to one of SEQ ID NOs: 85-87. In some embodiments of any of the aspects, the nucleic acid comprises a sequence withat least 98% sequence identity to one of SEQ ID NOs: 85-87. In some embodiments of any of the aspects, the nucleic acid comprises a sequence with at least 99% sequence identity to one of SEQ ID NOs: 85-87. In some embodiments of any of the aspects, the nucleic acid comprises a sequence identical to one of SEQ ID NOs: 85-87.

[0194] In some embodiments of any of the aspects, the nucleic acid comprises a sequence with at least 70% sequence identity to SEQ ID NO: 85. In some embodiments of any of the aspects, the nucleic acid comprises a sequence with at least 75% sequence identity to SEQ ID NO: 85. In some embodiments of any of the aspects, the nucleic acid comprises a sequence with at least 80% sequence identity to SEQ ID NO: 85. In some embodiments of any of the aspects, the nucleic acid comprises a sequence with at least 85% sequence identity to SEQ ID NO: 85. In some embodiments of any of the aspects, the nucleic acid comprises a sequence with at least 90% sequence identity to SEQ ID NO: 85. In some embodiments of any of tire aspects, the nucleic acid comprises a sequence with at least 95% sequence identity to SEQ ID NO: 85. In some embodiments of any of the aspects, the nucleic acid comprises a sequence with at least 98% sequence identity to SEQ ID NO: 85. In some embodiments of any of the aspects, the nucleic acid comprises a sequence with at least 99% sequence identity to SEQ ID NO: 85. In some embodiments of any of the aspects, the nucleic acid comprises a sequence identical to SEQ ID NO: 85.

[0195] In some embodiments of any of the aspects, the nucleic acid comprises a sequence with at least 70% sequence identity to SEQ ID NO: 86. In some embodiments of any of the aspects, the nucleic acid comprises a sequence with at least 75% sequence identity to SEQ ID NO: 86. In some embodiments of any of the aspects, the nucleic acid comprises a sequence with at least 80% sequence identity to SEQ ID NO: 86. In some embodiments of any of the aspects, the nucleic acid comprises a sequence with at least 85% sequence identity to SEQ ID NO: 86. In some embodiments of any of the aspects, the nucleic acid comprises a sequence with at least 90% sequence identity to SEQ ID NO: 86. In some embodiments of any of the aspects, the nucleic acid comprises a sequence w ith at least 95% sequence identity to SEQ ID NO: 86. In some embodiments of any of the aspects, the nucleic acid comprises a sequence with at least 98% sequence identity to SEQ ID NO: 86. In some embodiments of any of the aspects, the nucleic acid comprises a sequence with at least 99% sequence identity' to SEQ ID NO: 86. In some embodiments of any of the aspects, the nucleic acid comprises a sequence identical to SEQ ID NO: 86.

[0196] In some embodiments of any of the aspects, the nucleic acid comprises a sequence with at least 70% sequence identity to SEQ ID NO: 87. In some embodiments of any of the aspects, the nucleic acid comprises a sequence with at least 75% sequence identity to SEQ ID NO: 87. In some embodiments of any of the aspects, the nucleic acid comprises a sequence with at least 80% sequence identity to SEQ ID NO: 87. In some embodiments of any of the aspects, the nucleic acid comprises a sequence with at least 85% sequence identity to SEQ ID NO: 87. In some embodiments of any of theaspects, the nucleic acid comprises a sequence with at least 90% sequence identity to SEQ ID NO: 87.In some embodiments of any of the aspects, the nucleic acid comprises a sequence with at least 95% sequence identity to SEQ ID NO: 87. In some embodiments of any of the aspects, the nucleic acid comprises a sequence with at least 98% sequence identity' to SEQ ID NO: 87. In some embodiments of any of the aspects, the nucleic acid comprises a sequence with at least 99% sequence identity to SEQ ID NO: 87. In some embodiments of any of the aspects, the nucleic acid comprises a sequence identical to SEQ ID NO: 87.

[0197] In some embodiments of any of the aspects, the nucleic acid comprises a sequence which is codon-optimized for expression in human cells.

[0198] In some embodiments of any of the aspects, the portion of the nucleic acid encoding the utrophin NT domain comprises a codon-optimized sequence selected from one of SEQ ID NOs: 400- 412, or a sequence having at least 70%. at least 75%, at least 80%, at least 85%. at least 90%, at least 95%, at least 98%. or at least 99% sequence identity to one of the foregoing sequences.

[0199] In some embodiments of any of the aspects, the portion of the nucleic acid encoding the utrophin NT domain comprises the codon-optimized sequence of SEQ ID NO: 400, or a sequence having at least 70%, at least 75%. at least 80%, at least 85%, at least 90%. at least 95%, at least 98%, or at least 99% sequence identity to SEQ ID NO: 400. In some embodiments of any of the aspects, the portion of the nucleic acid encoding the utrophin NT domain comprises the codon-optimized sequence of SEQ ID NO: 400.

[0200] SEQ ID NO: 400 Codon-optimized sequence encoding utrophin NT domainATGGCCAAGTACGGCGAGCACGAGGCCTCCCCCGACAACGGCCAGAACGAGTTCTCCGACATCATCAA GTCCCGCTCCGACGAGCACAACGACGTGCAGAAGAAGACCTTCACCAAGTGGATCAACGCCCGCTTCT CCAAGTCCGGCAAGCCCCCCATCAACGACATGTTCACCGACCTGAAGGACGGCCGCAAGCTGCTGGAC CTGCTGGAGGGCCTGACCGGCACCTCCCTGCCCAAGGAGCGCGGCTCCACCCGCGTGCACGCCCTGAA CAACGTGAACCGCGTGCTGCAGGTGCTGCACCAGAACAACGTGGAGCTGGTGAACATCGGCGGCACCG ACATCGTGGACGGCAACCACAAGCTGACCCTGGGCCTGCTGTGGTCCATCATCCTGCACTGGCAGGTG AAGGACGTGATGAAGGACGTGATGTCCGACCTGCAGCAGACCAACTCCGAGAAGATCCTGCTGTCCTG GGTGCGCCAGACCACCCGCCCCTACTCCCAGGTGAACGTGCTGAACTTCACCACCTCCTGGACCGACG GCCTGGCCTTCAACGCCGTGCTGCACCGCCACAAGCCCGACCTGTTCTCCTGGGACAAGGTGGTGAAG ATGTCCCCCATCGAGCGCCTGGAGCACGCCTTCTCCAAGGCCCAGACCTACCTGGGCATCGAGAAGCT GCTGGACCCCGAGGACGTGGCCGTGCAGCTGCCCGACAAGAAGTCCATCATCATGTAC

[0201] In some embodiments of any of the aspects, the portion of the nucleic acid encoding the utrophin NT domain comprises the codon-optimized sequence of SEQ ID NO: 401, or a sequence having at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, or at least 99% sequence identity to SEQ ID NO: 401. In some embodiments of any of the aspects, the portion of the nucleic acid encoding the utrophin NT domain comprises the codon-optimized sequence of SEQ ID NO: 401.

[0202] SEQ ID NO: 401 Codon-optimized sequence encoding utrophin NT domainATGGCCAAGTACGGCGAGCACGAGGCCTCCCCCGACAACGGCCAGAACGAGTTCTCCGACATCATCAA GTCCCGCTCCGACGAGCACAACGACGTGCAGAAGAAGACCTTCACCAAGTGGATCAACGCCCGCTTCT CCAAGTCCGGCAAGCCCCCCATCAACGACATGTTCACCGACCTGAAGGACGGCCGCAAGCTGCTGGAC CTGCTGGAGGGCCTGACCGGCACCTCCCTGCCCAAGGAGCGCGGCTCCACCCGCGTGCACGCCCTGAA CAACGTGAACCGCGTGCTGCAGGTGCTGCACCAGAACAACGTGGAGCTGGTGAACATCGGCGGCACCG ACATCGTGGACGGCAACCACAAGCTGACCCTGGGCCTGCTGTGGTCCATCATCCTGCACTGGCAGGTG AAGGACGTGATGAAGGACGTGATGTCCGACCTGCAGCAGACCAACTCCGAGAAGATCCTGCTGTCCTG GGTGCGCCAGACCACCCGCCCCTACTCCCAGGTGAACGTGCTGAACTTCACCACCTCCTGGACCGACG GCCTGGCCTTCAACGCCGTGCTGCACCGCCACAAGCCCGACCTGTTCTCCTGGGACAAGGTGGTGAAG ATGTCCCCCATCGAGCGCCTGGAGCACGCCTTCTCCAAGGCCCAGACCTACCTGGGCATCGAGAAGCT GCTGGACCCCGAGGACGTGGCCGTGCAGCTGCCCGACAAGAAGTCCATCATCATGTACCTGACCTCCCTGTTCGAGGTGCTGCCCCAG CAGGTGACCATCGACGCCATCCGCGAGGTGGAG

[0203] In some embodiments of any of the aspects, the portion of the nucleic acid encoding the utrophin NT domain comprises the codon-optimized sequence of SEQ ID NO: 402, or a sequence having at least 70%. at least 75%, at least 80%, at least 85%. at least 90%, at least 95%, at least 98%. or at least 99% sequence identity to SEQ ID NO: 402. In some embodiments of any of the aspects, the portion of the nucleic acid encoding the utrophin NT domain comprises the codon-optimized sequence of SEQ ID NO: 402.

[0204] SEQ ID NO: 402 Codon-optimized sequence encoding utrophin NT domainATCAACGCCCGGTTCAGCAAGAGCGGCAAGCCCCCCATCAACGACATGTTCACCGACCTGAAGGACGG CCGGAAGCTGCTGGACCTGCTGGAGGGCCTGACCGGCACCAGCCTGCCCAAGGAGCGGGGCAGCACCC GGGTGCACGCCCTGAACAACGTGAACCGGGTGCTGCAGGTGCTGCACCAGAACAACGTGGAGCTGGTG AACATCGGCGGCACCGACATCGTGGACGGCAACCACAAGCTGACCCTGGGCCTGCTGTGGAGCATCAT CCTGCACTGGCAGGTGAAGGACGTGATGAAGGACGTGATGAGCGACCTGCAGCAGACCAACAGCGAGA AGATCCTGCTGAGCTGGGTGCGGCAGACCACCCGGCCCTACAGCCAGGTGAACGTGCTGAACTTCACC ACCAGCTGGACCGACGGCCTGGCCTTCAACGCCGTGCTGCACCGGCACAAGCCCGACCTGTTCAGCTG GGACAAGGTGGTGAAGATGAGCCCCATCGAGCGGCTGGAGCACGCCTTCAGCAAGGCCCAGACCTACC TGGGCATCGAGAAGCTGCTGGACCCCGAGGACGTGGCCGTGCAGCTGCCCGACAAGAAGAGCATCATC ATGTACCTGACCAGCCTGTTCGAGGTGCTGCCCCAGCAGGTGACCATCGACGCCATCCGGGAGGTGGA G

[0205] In some embodiments of any of the aspects, the portion of the nucleic acid encoding the utrophin NT domain comprises the codon-optimized sequence of SEQ ID NO: 403, or a sequence having at least 70%, at least 75%. at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, or at least 99% sequence identity’ to SEQ ID NO: 403. In some embodiments of any of the aspects, the portion of the nucleic acid encoding the utrophin NT domain comprises the codon-optimized sequence of SEQ ID NO: 403.

[0206] SEQ ID NO: 403 Codon-optimized sequence encoding utrophin NTATGGCCAAGTACGGCGAGCACGAGGCCTCCCCTGACAACGGCCAGAACGAGTTCTCCGACATCATCAA GTCCAGGTCCGACGAGCACAACGACGTGCAGAAGAAGACCTTCACCAAGTGGATCAACGCCAGGTTCT CCAAGTCCGGCAAGCCTCCTATCAACGACATGTTCACCGACCTGAAGGACGGCAGGAAGCTGCTGGAC CTGCTGGAGGGCCTGACCGGCACCTCCCTGCCTAAGGAGAGGGGCTCCACCAGGGTGCACGCCCTGAA CAACGTGAACAGGGTGCTGCAGGTGCTGCACCAGAACAACGTGGAGCTGGTGAACATCGGCGGCACCG ACATCGTGGACGGCAACCACAAGCTGACCCTGGGCCTGCTGTGGTCCATCATCCTGCACTGGCAGGTG AAGGACGTGATGAAGGACGTGATGTCCGACCTGCAGCAGACCAACTCCGAGAAGATCCTGCTGTCCTG GGTGAGGCAGACCACCAGGCCTTACTCCCAGGTGAACGTGCTGAACTTCACCACCTCCTGGACCGACGGCCTGGCCTTCAACGCCGTGCTGCACAGGCACAAGCCTGACCTGTTCTCCTGGGACAAGGTGGTGAAG ATGTCCCCTATCGAGAGGCTGGAGCACGCCTTCTCCAAGGCCCAGACCTACCTGGGCATCGAGAAGCT GCTGGACCCTGAGGACGTGGCCGTGCAGCTGCCTGACAAGAAGTCCATCATCATGTACCTGACCTCCC TGTTCGAGGTGCTGCCTCAGCAGGTGACCATCGACGCCATCAGGGAGGTGGAG

[0207] In some embodiments of any of the aspects, the portion of the nucleic acid encoding the utrophin NT domain comprises the codon-optimized sequence of SEQ ID NO: 404, or a sequence having at least 70%. at least 75%, at least 80%, at least 85%. at least 90%, at least 95%, at least 98%. or at least 99% sequence identity to SEQ ID NO: 404. In some embodiments of any of the aspects, the portion of the nucleic acid encoding the utrophin NT domain comprises the codon-optimized sequence of SEQ ID NO: 404.

[0208] SEQ ID NO: 404 Codon-optimized sequence encoding utrophin NTATGGCCAAGTACGGCGAGCACGAGGCCTCCCCCGACAACGGCCAGAACGAGTTCTCCGACATCATCAA GTCCAGGTCCGACGAGCACAACGACGTGCAGAAGAAGACCTTCACCAAGTGGATCAACGCCAGGTTCT CCAAGTCCGGCAAGCCCCCCATCAACGACATGTTCACCGACCTGAAGGACGGCAGGAAGCTGCTGGAC CTGCTGGAGGGCCTGACCGGCACCTCCCTGCCCAAGGAGAGGGGCTCCACCAGGGTGCACGCCCTGAA CAACGTGAACAGGGTGCTGCAGGTGCTGCACCAGAACAACGTGGAGCTGGTGAACATCGGCGGCACCG ACATCGTGGACGGCAACCACAAGCTGACCCTGGGCCTGCTGTGGTCCATCATCCTGCACTGGCAGGTG AAGGACGTGATGAAGGACGTGATGTCCGACCTGCAGCAGACCAACTCCGAGAAGATCCTGCTGTCCTG GGTGAGGCAGACCACCAGGCCCTACTCCCAGGTGAACGTGCTGAACTTCACCACCTCCTGGACCGACG GCCTGGCCTTCAACGCCGTGCTGCACAGGCACAAGCCCGACCTGTTCTCCTGGGACAAGGTGGTGAAG ATGTCCCCCATCGAGAGGCTGGAGCACGCCTTCTCCAAGGCCCAGACCTACCTGGGCATCGAGAAGCT GCTGGACCCCGAGGACGTGGCCGTGCAGCTGCCCGACAAGAAGTCCATCATCATGTACCTGACCTCCC TGTTCGAGGTGCTGCCCCAGCAGGTGACCATCGACGCCATCAGGGAGGTGGAG

[0209] In some embodiments of any of the aspects, the portion of the nucleic acid encoding the utrophin NT domain comprises the codon-optimized sequence of SEQ ID NO: 405, or a sequence having at least 70%, at least 75%. at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, or at least 99% sequence identity to SEQ ID NO: 405. In some embodiments of any of the aspects, the portion of the nucleic acid encoding the utrophin NT domain comprises the codon-optimized sequence of SEQ ID NO: 405.

[0210] SEQ ID NO: 405 Codon-optimized sequence encoding utrophin NTATGGCCAAGTATGGGGAGCATGAGGCTAGTCCTGACAATGGGCAGAATGAATTCAGTGACATCATTAA GTCTAGGTCAGATGAGCACAATGATGTACAGAAGAAAACCTTTACTAAATGGATAAATGCCAGGTTTT CAAAGAGTGGGAAACCACCCATCAATGATATGTTCACTGACCTCAAAGATGGCAGGAAGCTATTGGAT CTTCTAGAGGGCCTCACAGGTACATCACTGCCAAAGGAAAGGGGTTCCACAAGAGTACATGCATTAAA TAATGTCAACAGGGTGCTGCAGGTTTTACATCAGAACAATGTGGAATTAGTGAATATAGGAGGAACTG ACATAGTGGATGGAAATCACAAACTGACATTGGGGTTACTTTGGAGCATCATTTTGCACTGGCAGGTG AAAGATGTGATGAAGGATGTCATGTCTGACCTGCAGCAGACCAACTCAGAGAAGATCCTGCTCAGCTG GGTGAGGCAGACTACCAGGCCCTACTCTCAAGTCAATGTGCTCAACTTCACCACCAGCTGGACAGATG GCCTGGCCTTTAATGCAGTGCTCCACAGGCATAAACCTGACCTCTTCAGCTGGGATAAAGTTGTCAAA ATGTCACCAATTGAGAGACTTGAACATGCTTTCAGCAAGGCTCAAACATATTTGGGAATAGAGAAGCT GTTAGATCCTGAAGATGTTGCAGTTCAGCTTCCAGACAAGAAAAGTATAATTATGTATTTAACTAGTT TGTTTGAGGTGCTACCTCAGCAAGTCACCATAGATGCCATCAGGGAGGTAGAG

[0211] In some embodiments of any of the aspects, the portion of the nucleic acid encoding the utrophin NT domain comprises the codon-optimized sequence of SEQ ID NO: 406, or a sequence having at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, or at least 99% sequence identity to SEQ ID NO: 406. In some embodiments of any of the aspects, the portion of the nucleic acid encoding the utrophin NT domain comprises the codon-optimized sequence of SEQ ID NO: 406.

[0212] SEQ ID NO: 406 Codon-optimized sequence encoding utrophin NTATGGCTAAGTATGGAGAGCATGAGGCCAGTCCAGACAATGGCCAGAATGAATTCAGTGACATCATTAA GTCCAGGTCTGATGAACACAATGATGTACAGAAGAAAACCTTTACCAAATGGATAAATGCCAGGTTTA GCAAGAGTGGCAAACCACCCATCAATGATATGTTCACTGACCTCAAAGATGGCAGGAAGCTATTGGAT CTTCTAGAAGGCCTCACAGGAACATCACTGCCAAAGGAAAGAGGTTCCACCAGGGTACATGCTTTAAA TAATGTCAACAGGGTGCTGCAGGTTTTACATCAGAACAATGTGGAGTTAGTGAATATAGGAGGAACTG ACATAGTGGATGGCAATCACAAACTGACATTGGGGTTACTTTGGAGCATCATTTTGCACTGGCAGGTG AAAGATGTCATGAAGGATGTAATGTCAGACCTGCAGCAGACCAACAGTGAGAAGATCCTGCTCAGCTG GGTGAGGCAGACAACCAGGCCCTACAGTCAAGTCAATGTCCTCAACTTCACCACCAGCTGGACTGATG GACTGGCATTTAATGCTGTGCTCCACAGGCATAAACCTGACCTCTTCAGCTGGGATAAAGTTGTCAAA ATGTCACCAATTGAGAGGCTTGAACATGCCTTCAGCAAGGCTCAAACTTATTTGGGAATAGAGAAGCT GTTAGACCCAGAAGATGTGGCTGTGCAGCTTCCTGACAAGAAATCAATAATTATGTATTTAACTAGCT TGTTTGAGGTGCTACCACAGCAAGTCACCATAGATGCAATCAGAGAGGTAGAG

[0213] In some embodiments of any of the aspects, the portion of the nucleic acid encoding the utrophin NT domain comprises the codon-optimized sequence of SEQ ID NO: 407, or a sequence having at least 70%, at least 75%. at least 80%, at least 85%, at least 90%. at least 95%, at least 98%, or at least 99% sequence identity to SEQ ID NO: 407. In some embodiments of any of the aspects, the portion of the nucleic acid encoding the utrophin NT domain comprises the codon-optimized sequence of SEQ ID NO: 407.

[0214] SEQ ID NO: 407 Codon-optimized sequence encoding utrophin NTATGGCTAAGTATGGGGAGCATGAGGCCAGTCCAGACAATGGACAGAATGAGTTCAGTGACATCATTAA GTCTAGGTCAGATGAGCACAATGATGTCCAGAAGAAAACCTTTACTAAATGGATAAATGCCAGATTTA GCAAGAGTGGGAAACCACCCATCAATGACATGTTCACTGACCTCAAAGATGGCAGGAAGCTATTGGAT CTTCTAGAGGGCCTCACTGGAACATCACTGCCAAAGGAAAGGGGTTCCACCAGGGTACATGCCTTAAA TAATGTCAACAGGGTGCTGCAGGTTTTACATCAGAACAATGTGGAATTAGTGAATATAGGAGGAACTG ACATAGTGGATGGCAATCACAAACTGACTTTGGGGTTACTTTGGAGCATCATTTTGCACTGGCAGGTG AAAGATGTGATGAAGGATGTGATGTCAGACCTGCAGCAGACCAACTCAGAAAAGATCCTGCTCAGCTG GGTGAGGCAGACAACCAGGCCCTACTCCCAAGTCAATGTCCTCAACTTCACCACCAGCTGGACAGATG GCCTGGCATTTAATGCTGTCCTCCACAGGCATAAACCAGACCTCTTCAGCTGGGATAAAGTTGTCAAA ATGTCACCAATAGAGAGGCTTGAACATGCTTTCAGCAAGGCTCAAACATATTTGGGAATAGAAAAGCT GCTGGATCCTGAAGATGTGGCTGTCCAGCTTCCTGACAAGAAATCAATAATTATGTATTTAACAAGCT TGTTTGAGGTGCTACCACAGCAAGTCACCATAGATGCAATCAGAGAGGTAGAG

[0215] In some embodiments of any of the aspects, the portion of the nucleic acid encoding the utrophin NT domain comprises the codon-optimized sequence of SEQ ID NO: 408, or a sequence having at least 70%, at least 75%. at least 80%, at least 85%, at least 90%, at least 95%, at least 98%,or at least 99% sequence identity to SEQ ID NO: 408. In some embodiments of any of the aspects, the portion of the nucleic acid encoding the utrophin NT domain comprises the codon-optimized sequence of SEQ ID NO: 408.

[0216] SEQ ID NO: 408 Codon-optimized sequence encoding utrophin NTATGGCAAAGTATGGGGAGCATGAAGCAAGTCCAGACAATGGACAGAATGAATTCTCAGATATCATTAA GTCCAGGTCTGATGAACACAATGATGTACAGAAGAAAACCTTTACCAAATGGATAAATGCCAGGTTTA GCAAGAGTGGCAAACCACCCATCAATGATATGTTCACTGACCTCAAAGATGGAAGGAAGCTATTGGAT CTTCTGGAAGGCCTCACTGGAACATCACTGCCAAAGGAAAGGGGTTCCACCAGAGTACATGCCTTAAA TAATGTCAACAGGGTGCTGCAGGTTTTACATCAGAACAATGTTGAATTAGTGAATATAGGTGGCACTG ATATAGTTGATGGGAATCACAAACTGACCTTGGGGTTACTTTGGAGCATCATTTTGCACTGGCAGGTG AAAGATGTCATGAAGGATGTGATGTCTGACCTGCAGCAGACAAACAGTGAGAAGATCCTGCTCAGCTG GGTGAGGCAGACCACCAGACCCTACAGCCAAGTCAATGTCCTCAACTTCACCACCAGCTGGACAGATG GCCTGGCTTTTAATGCAGTGCTCCACAGGCATAAACCAGATCTCTTCAGCTGGGATAAAGTTGTCAAA ATGTCACCAATAGAAAGGCTTGAACATGCCTTCAGCAAGGCTCAAACCTATTTGGGAATAGAGAAGCT GTTAGACCCAGAAGATGTTGCAGTCCAGCTTCCTGACAAGAAATCTATAATTATGTATTTAACTTCCT TGTTTGAGGTGCTACCCCAGCAAGTCACCATAGATGCCATCAGGGAGGTAGAG

[0217] In some embodiments of any of the aspects, the portion of the nucleic acid encoding the utrophin NT domain comprises the codon-optimized sequence of SEQ ID NO: 409, or a sequence having at least 70%, at least 75%. at least 80%, at least 85%, at least 90%. at least 95%, at least 98%, or at least 99% sequence identity to SEQ ID NO: 409. In some embodiments of any of the aspects, the portion of the nucleic acid encoding the utrophin NT domain comprises the codon-optimized sequence of SEQ ID NO: 409.

[0218] SEQ ID NO: 409 Codon-optimized sequence encoding utrophin NTATGGCCAAGTATGGGGAACATGAAGCCAGTCCAGACAATGGCCAGAATGAATTCAGTGATATCATTAA GTCCAGATCAGATGAGCACAATGATGTGCAGAAGAAAACCTTTACCAAATGGATAAATGCTAGGTTTT CAAAGTCAGGTAAACCACCCATCAATGACATGTTCACTGACCTCAAAGATGGAAGGAAGCTACTTGAT CTTCTAGAAGGCCTCACAGGAACATCACTGCCTAAGGAAAGAGGTTCCACAAGGGTACATGCCTTAAA TAATGTCAACAGAGTGCTGCAGGTTTTACATCAGAACAATGTGGAATTAGTTAATATTGGGGGCACTG ACATAGTGGATGGCAATCACAAACTGACTTTGGGGTTACTTTGGTCAATCATTTTGCACTGGCAGGTG AAAGATGTCATGAAGGATGTCATGTCAGACCTGCAGCAGACTAACTCTGAGAAGATCCTGCTCAGCTG GGTGAGGCAGACCACCAGGCCATACTCCCAAGTCAATGTGCTCAACTTCACCACCAGCTGGACAGATG GACTGGCCTTTAATGCTGTCCTCCACAGGCATAAACCTGATCTCTTCAGCTGGGATAAAGTTGTCAAA ATGTCACCAATTGAGAGACTTGAACATGCCTTCAGCAAGGCCCAAACATATTTGGGAATAGAAAAGCT GTTAGATCCAGAAGATGTTGCTGTTCAGCTTCCAGACAAGAAATCCATAATTATGTATTTAACATCTT TGTTTGAGGTGCTACCTCAGCAAGTCACCATAGATGCTATCAGGGAGGTAGAG

[0219] In some embodiments of any of the aspects, the portion of the nucleic acid encoding the utrophin NT domain comprises the codon-optimized sequence of SEQ ID NO: 410, or a sequence having at least 70%, at least 75%, at least 80%, at least 85%. at least 90%, at least 95%, at least 98%. or at least 99% sequence identity to SEQ ID NO: 410. In some embodiments of any of the aspects, the portion of the nucleic acid encoding the utrophin NT domain comprises the codon-optimized sequence of SEQ ID NO: 410.

[0220] SEQ ID NO: 410 Codon-optimized sequence encoding utrophin NTATGGCTAAGTATGGGGAACATGAGGCCAGTCCAGACAATGGGCAGAATGAATTCTCTGATATCATTAA GTCCAGATCTGATGAACACAATGATGTGCAGAAGAAAACCTTTACCAAATGGATAAATGCTAGATTTT CAAAGAGTGGGAAACCACCCATCAATGACATGTTCACTGACCTCAAAGATGGGAGAAAGCTACTAGAT CTTCTAGAAGGCCTCACTGGAACATCACTGCCCAAGGAAAGGGGTTCCACAAGGGTACATGCCTTAAA TAATGTCAACAGAGTGCTGCAGGTTTTACATCAGAACAATGTGGAACTGGTGAATATAGGTGGCACTG ACATTGTGGATGGCAATCACAAACTGACTTTGGGGTTACTTTGGTCTATCATTTTGCACTGGCAGGTG AAAGATGTCATGAAGGATGTGATGTCAGACCTGCAGCAGACAAACTCAGAAAAGATCCTGCTCAGCTG GGTGAGACAGACCACTAGGCCTTACAGTCAAGTCAATGTCCTCAACTTCACCACCAGCTGGACAGATG GCCTGGCCTTTAATGCTGTCCTCCACAGACATAAACCTGATCTCTTCAGCTGGGATAAAGTTGTCAAA ATGTCACCAATTGAGAGGCTTGAACATGCTTTCAGCAAGGCCCAAACTTATTTGGGAATTGAAAAGCT GTTAGATCCTGAAGATGTGGCAGTGCAGCTTCCAGACAAGAAATCCATAATTATGTATTTAACATCTT TGTTTGAGGTGCTACCTCAGCAAGTCACCATTGATGCCATCAGAGAGGTAGAG

[0221] In some embodiments of any of the aspects, the portion of the nucleic acid encoding the utrophin NT domain comprises the codon-optimized sequence of SEQ ID NO: 411. or a sequence having at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, or at least 99% sequence identity to SEQ ID NO: 411. In some embodiments of any of the aspects, the portion of the nucleic acid encoding the utrophin NT domain comprises the codon-optimized sequence of SEQ ID NO: 411.

[0222] SEQ ID NO: 411 Codon-optimized sequence encoding utrophin NTATGGCTAAGTATGGAGAACATGAAGCTAGTCCTGACAATGGGCAGAATGAGTTCAGTGACATCATTAA GTCCAGATCTGATGAGCACAATGATGTCCAGAAGAAAACCTTTACCAAATGGATAAATGCCAGGTTTT CAAAGAGTGGGAAACCACCTATCAATGATATGTTCACAGACCTCAAAGATGGAAGGAAGCTACTGGAT CTTCTAGAAGGCCTCACTGGGACATCACTGCCTAAGGAAAGGGGTTCCACAAGGGTACATGCTTTAAA TAATGTCAACAGGGTGCTGCAGGTTTTACATCAGAACAATGTGGAACTGGTGAATATTGGGGGTACAG ACATTGTGGATGGCAATCACAAACTGACTTTGGGGTTACTTTGGTCAATCATTTTGCACTGGCAGGTG AAAGATGTGATGAAGGATGTTATGTCTGACCTGCAGCAGACTAACAGTGAAAAGATCCTGCTCAGCTG GGTGAGGCAGACCACTAGGCCCTACTCCCAAGTCAATGTTCTCAACTTCACCACCTCTTGGACAGATG GCTTAGCCTTTAATGCTGTGCTCCACAGGCATAAACCAGACCTCTTCAGCTGGGATAAAGTTGTCAAA ATGTCACCAATTGAGAGACTTGAACATGCCTTCAGCAAGGCTCAAACCTATTTGGGAATTGAAAAGCT GTTAGATCCAGAAGATGTGGCTGTTCAGCTTCCAGACAAGAAATCCATAATTATGTATTTAACATCTT TGTTTGAAGTGCTACCTCAGCAAGTCACTATAGATGCTATCAGGGAGGTAGAG

[0223] In some embodiments of any of the aspects, the portion of the nucleic acid encoding the utrophin NT domain comprises the codon-optimized sequence of SEQ ID NO: 412, or a sequence having at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, at least 98%. or at least 99% sequence identity to SEQ ID NO: 412. In some embodiments of any of the aspects, the portion of the nucleic acid encoding the utrophin NT domain comprises the codon-optimized sequence of SEQ ID NO: 412.

[0224] SEQ ID NO: 412 Codon-optimized sequence encoding utrophin NTATGGCTAAGTATGGAGAACATGAGGCCAGTCCAGACAATGGGCAGAATGAGTTCAGTGACATCATTAA GTCCAGAAGTGATGAACACAATGATGTACAGAAGAAAACCTTTACCAAATGGATAAATGCTAGATTTT CAAAGTCTGGGAAACCACCTATCAATGATATGTTCACAGACCTCAAAGATGGCAGAAAGCTATTGGAC CTTCTAGAAGGCCTCACTGGCACATCACTGCCCAAGGAAAGAGGTTCCACAAGGGTACATGCATTAAA TAATGTTAACAGGGTGCTGCAGGTTTTACATCAGAACAATGTGGAACTGGTGAATATAGGTGGAACTG ATATTGTGGATGGCAATCACAAACTGACTTTGGGGTTACTTTGGAGTATCATTTTGCACTGGCAGGTGAAAGATGTTATGAAGGATGTGATGTCTGACCTGCAGCAGACCAACTCAGAGAAGATCCTGCTCAGCTG GGTGAGGCAGACCACTAGGCCATACTCCCAAGTCAATGTGCTCAACTTCACCACCTCCTGGACAGATG GCCTTGCCTTTAATGCTGTCCTCCACAGACATAAACCTGATCTCTTCAGCTGGGATAAAGTTGTCAAA ATGTCACCAATTGAGAGGCTTGAACATGCCTTCAGCAAGGCCCAAACTTATTTGGGAATTGAAAAGCT GTTAGATCCTGAAGATGTGGCTGTGCAGCTTCCAGACAAGAAATCCATAATTATGTATTTAACATCTT TGTTTGAGGTGCTACCTCAGCAAGTCACAATTGATGCTATCAGAGAGGTAGAG

[0225] In some embodiments of any of the aspects, the portion of the nucleic acid encoding the utrophin hinge 1 domain comprises a codon-optimized sequence selected from one of SEQ ID NOs: 413-424, or a sequence having at least 70%. at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, or at least 99% sequence identity to one of the foregoing sequences.

[0226] In some embodiments of any of the aspects, the portion of the nucleic acid encoding the utrophin hinge 1 domain comprises the codon-optimized sequence of SEQ ID NO: 413, or a sequence having at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, at least 98%. or at least 99% sequence identity to SEQ ID NO: 413. In some embodiments of any of the aspects, the portion of the nucleic acid encoding the utrophin hinge 1 domain comprises the codon-optimized sequence of SEQ ID NO: 413.

[0227] SEQ ID NO: 413 Codon-optimized sequence encoding utrophin hinge 1 domainACCCTGCCCCGCAAGTACAAGAAGGAGTGCGAGGAGGAGGCCATCAACATCCAGTCCACCGCCCCCGA GGAGGAGCACGAGTCCCCCCGCGCCGAGACCCCCTCCACC

[0228] In some embodiments of any of the aspects, the portion of the nucleic acid encoding the utrophin hinge 1 domain comprises the codon-optimized sequence of SEQ ID NO: 414, or a sequence having at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, at least 98%. or at least 99% sequence identity to SEQ ID NO: 414. In some embodiments of any of the aspects, the portion of the nucleic acid encoding the utrophin hinge 1 domain comprises the codon-optimized sequence of SEQ ID NO: 414.

[0229] SEQ ID NO: 414 Codon-optimized sequence encoding utrophin hinge 1 domainACCCTGCCCCGGAAGTACAAGAAGGAGTGCGAGGAGGAGGCCATCAACATCCAGAGCACCGCCCCCGA GGAGGAGCACGAGAGCCCCC

[0230] In some embodiments of any of the aspects, the portion of the nucleic acid encoding the utrophin hinge 1 domain comprises the codon-optimized sequence of SEQ ID NO: 415, or a sequence having at least 70%, at least 75%. at least 80%, at least 85%, at least 90%. at least 95%, at least 98%, or at least 99% sequence identity to SEQ ID NO: 415. In some embodiments of any of the aspects, the portion of the nucleic acid encoding the utrophin hinge 1 domain comprises the codon-optimized sequence of SEQ ID NO: 415.

[0231] SEQ ID NO: 415 Codon-optimized sequence encoding utrophin hinge 1 domainACCCTGCCTAGGAAGTACAAGAAGGAGTGCGAGGAGGAGGCCATCAACATCCAGTCCACCGCCCCTGA GGAGGAGCACGAGTCCCCTAGGGCCGAGACCCCTTCCACC

[0232] In some embodiments of any of the aspects, the portion of the nucleic acid encoding the utrophin hinge 1 domain comprises the codon-optimized sequence of SEQ ID NO: 416, or a sequence having at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, or at least 99% sequence identity to SEQ ID NO: 416. In some embodiments of any of the aspects, the portion of the nucleic acid encoding the utrophin hinge 1 domain comprises the codon-optimized sequence of SEQ ID NO: 416.

[0233] SEQ ID NO: 416 Codon-optimized sequence encoding utrophin hinge 1 domainACCCTGCCCAGGAAGTACAAGAAGGAGTGCGAGGAGGAGGCCATCAACATCCAGTCCACCGCCCCCGA GGAGGAGCACGAGTCCCCCAGGGCCGAGACCCCCTCCACC

[0234] In some embodiments of any of the aspects, the portion of the nucleic acid encoding the utrophin hinge 1 domain comprises the codon-optimized sequence of SEQ ID NO: 417, or a sequence having at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, or at least 99% sequence identity to SEQ ID NO: 417. In some embodiments of any of the aspects, the portion of the nucleic acid encoding the utrophin hinge 1 domain comprises the codon-optimized sequence of SEQ ID NO: 417.

[0235] SEQ ID NO: 417 Codon-optimized sequence encoding utrophin hinge 1 domainACCCTCCCAAGGAAATATAAAAAAGAATGTGAGGAAGAGGCTATTAATATACAGAGCACAGCACCTGA GGAGGAGCATGAGAGTCCCAGGGCTGAGACACCTAGCACT

[0236] In some embodiments of any of the aspects, the portion of the nucleic acid encoding the utrophin hinge 1 domain comprises the codon-optimized sequence of SEQ ID NO: 418, or a sequence having at least 70%, at least 75%, at least 80%, at least 85%. at least 90%, at least 95%, at least 98%. or at least 99% sequence identity to SEQ ID NO: 418. In some embodiments of any of the aspects, the portion of the nucleic acid encoding the utrophin hinge 1 domain comprises the codon-optimized sequence of SEQ ID NO: 418.

[0237] SEQ ID NO: 418 Codon-optimized sequence encoding utrophin hinge 1 domain ACCCTCCCAAGGAAATATAAAAAAGAATGTGAGGAAGAGGCCATTAATATACAGTCCACAGCACCAGA GGAGGAGCATGAGAGTCCCAGGGCTGAAACTCCCAGCACT

[0238] In some embodiments of any of the aspects, the portion of the nucleic acid encoding the utrophin hinge 1 domain comprises the codon-optimized sequence of SEQ ID NO: 419, or a sequence having at least 70%, at least 75%. at least 80%, at least 85%, at least 90%. at least 95%, at least 98%, or at least 99% sequence identity to SEQ ID NO: 419. In some embodiments of any of the aspects, the portion of the nucleic acid encoding the utrophin hinge 1 domain comprises the codon-optimized sequence of SEQ ID NO: 419.

[0239] SEQ ID NO: 419 Codon-optimized sequence encoding utrophin hinge 1 domainACCCTCCCAAGGAAATATAAAAAAGAATGTGAAGAAGAGGCTATTAATATACAGTCCACTGCCCCAGA GGAGGAGCATGAGAGTCCTAGGGCAGAGACCCCAAGCACT

[0240] In some embodiments of any of the aspects, the portion of the nucleic acid encoding the utrophin hinge 1 domain comprises the codon-optimized sequence of SEQ ID NO: 420, or a sequence having at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, or at least 99% sequence identity to SEQ ID NO: 420. In some embodiments of any of the aspects, the portion of the nucleic acid encoding the utrophin hinge 1 domain comprises the codon-optimized sequence of SEQ ID NO: 420.

[0241] SEQ ID NO: 420 Codon-optimized sequence encoding utrophin hinge 1 domainACCCTCCCAAGGAAATATAAAAAAGAATGTGAGGAAGAGGCCATTAATATACAGAGCACAGCTCCAGA GGAGGAGCATGAGAGTCCAAGGGCTGAGACCCCTAGCACA

[0242] In some embodiments of any of the aspects, the portion of the nucleic acid encoding the utrophin hinge 1 domain comprises the codon -optimized sequence of SEQ ID NO: 421, or a sequence having at least 70%. at least 75%, at least 80%, at least 85%. at least 90%, at least 95%, at least 98%. or at least 99% sequence identity to SEQ ID NO: 421. In some embodiments of any of the aspects, the portion of the nucleic acid encoding the utrophin hinge 1 domain comprises the codon-optimized sequence of SEQ ID NO: 421.

[0243] SEQ ID NO: 421 Codon-optimized sequence encoding utrophin hinge 1 domain ACCCTCCCAAGGAAATATAAAAAAGAATGTGAGGAAGAGGCAATTAATATACAGTCTACTGCTCCTGA GGAGGAGCATGAGAGTCCCAGAGCAGAAACTCCCAGCACA

[0244] In some embodiments of any of the aspects, the portion of the nucleic acid encoding the utrophin hinge 1 domain comprises the codon-optimized sequence of SEQ ID NO: 422, or a sequence having at least 70%. at least 75%, at least 80%, at least 85%. at least 90%, at least 95%, at least 98%. or at least 99% sequence identity to SEQ ID NO: 422. In some embodiments of any of the aspects, the portion of the nucleic acid encoding the utrophin hinge 1 domain comprises the codon-optimized sequence of SEQ ID NO: 422.

[0245] SEQ ID NO: 422 Codon-optimized sequence encoding utrophin hinge 1 domain ACTCTCCCAAGGAAATATAAAAAAGAATGTGAGGAAGAGGCAATTAATATACAGTCCACAGCCCCTGA GGAGGAGCATGAGAGTCCCAGAGCTGAGACTCCCAGCACA

[0246] In some embodiments of any of the aspects, the portion of the nucleic acid encoding the utrophin hinge 1 domain comprises the codon -optimized sequence of SEQ ID NO: 423, or a sequence having at least 70%. at least 75%, at least 80%, at least 85%. at least 90%, at least 95%, at least 98%. or at least 99% sequence identity to SEQ ID NO: 423. In some embodiments of any of the aspects, the portion of the nucleic acid encoding the utrophin hinge 1 domain comprises the codon-optimized sequence of SEQ ID NO: 423.

[0247] SEQ ID NO: 423 Codon-optimized sequence encoding utrophin hinge 1 domainAC AC T C C C T AGGAAAT AT AAAAAAGAAT GT GAAGAAGAGGC AAT TAATATACAGAGTACAGCCC C AGA AGAGGAGCATGAGAGTCCCAGGGCTGAGACTCCCAGCACT

[0248] In some embodiments of any of the aspects, the portion of the nucleic acid encoding the utrophin hinge 1 domain comprises the codon-optimized sequence of SEQ ID NO: 424, or a sequence having at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, or at least 99% sequence identity to SEQ ID NO: 424. In some embodiments of any of the aspects, the portion of the nucleic acid encoding the utrophin hinge 1 domain comprises the codon-optimized sequence of SEQ ID NO: 424.

[0249] SEQ ID NO: 424 Codon-optimized sequence encoding utrophin hinge 1 domainACCCTCCCCAGGAAATATAAAAAAGAATGTGAGGAAGAGGCAATTAATATACAGAGCACAGCTCCAGA GGAGGAGCATGAGAGTCCCAGGGCAGAGACTCCCAGCACT

[0250] In some embodiments of any of the aspects, the portion of the nucleic acid encoding the utrophin SLR1 domain comprises a codon-optimized sequence selected from one of SEQ ID NOs: 425-438, or a sequence having at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, or at least 99% sequence identity to one of the foregoing sequences. In some embodiments of any of the aspects, the portion of the nucleic acid encoding the utrophin SLR1 domain comprises a codon-optimized sequence selected from one of SEQ ID NOs: 425-432 and 434- 438, or a sequence having at least 70%, at least 75%, at least 80%, at least 85%. at least 90%, at least 95%, at least 98%. or at least 99% sequence identity to one of the foregoing sequences.

[0251] In some embodiments of any of the aspects, the portion of the nucleic acid encoding the utrophin SLR1 domain comprises the codon-optimized sequence of SEQ ID NO: 425. or a sequence having at least 70%. at least 75%, at least 80%, at least 85%. at least 90%, at least 95%, at least 98%. or at least 99% sequence identity to SEQ ID NO: 425. In some embodiments of any of the aspects, the portion of the nucleic acid encoding the utrophin SLR1 domain comprises the codon-optimized sequence of SEQ ID NO: 425.

[0252] SEQ ID NO: 425 Codon-optimized sequence encoding utrophin SLR1 domainGACTCCTACCAGATCGCCCTGGAGGAGGTGCTGACCTGGCTGCTGTCCGCCGAGGACACCTTCCAGGA GCAGGACGACATCTCCGACGACGTGGAGGAGGTGAAGGACCAGTTCGCCACCCACGAGGCCTTCATGA TGGAGCTGACCGCCCACCAGTCCTCCGTGGGCTCCGTGCTGCAGGCCGGCAACCAGCTGATCACCCAG GGCACCCTGTCCGACGAGGAGGAGTTCGAGATCCAGGAGCAGATGACCCTGCTGAACGCCCGCTGGGA GGCCCTGCGCGTGGAGTCCATGGACCGCCAGTCCCGCCTGCAC

[0253] In some embodiments of any of the aspects, the portion of the nucleic acid encoding the utrophin SLR1 domain comprises the codon-optimized sequence of SEQ ID NO: 426. or a sequence having at least 70%. at least 75%, at least 80%, at least 85%. at least 90%, at least 95%, at least 98%. or at least 99% sequence identity to SEQ ID NO: 426. In some embodiments of any of the aspects, the portion of the nucleic acid encoding the utrophin SLR1 domain comprises the codon-optimized sequence of SEQ ID NO: 426.

[0254] SEQ ID NO: 426 Codon-optimized sequence encoding utrophin SLR1 domainCTACCAGATCGCCCTGGAGGAGGTGCTGACCTGGCTGCTGAGCGCCGAGGACACCTTCCAGGAGCAGG ACGACATCAGCGACGACGTGGAGGAGGTGAAGGACCAGTTCGCCACCCACGAGGCCTTCATGATGGAG CTGACCGCCCACCAGAGCAGCGTGGGCAGCGTGCTGCAGGCCGGCAACCAGCTGATCACCCAGGGCAC CCTGAGCGACGAGGAGGAGTTCGAGATCCAGGAGCAGATGACCCTGCTGAACGCCCGGTGGGAGGCCC TGCGGGTGGAGAGCATGGACCGGCAGAGCCGGCTGCAC

[0255] In some embodiments of any of the aspects, the portion of the nucleic acid encoding the utrophin SLR1 domain comprises the codon-optimized sequence of SEQ ID NO: 427, or a sequence having at least 70%, at least 75%. at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, or at least 99% sequence identity’ to SEQ ID NO: 427. In some embodiments of any of the aspects, the portion of the nucleic acid encoding the utrophin SLR1 domain comprises the codon-optimized sequence of SEQ ID NO: 427.

[0256] SEQ ID NO: 427 Codon-optimized sequence encoding utrophin SLR1 domainGACTCCTACCAGATCGCCCTGGAGGAGGTGCTGACCTGGCTGCTGTCCGCCGAGGACACCTTCCAGGA GCAGGACGACATCTCCGACGACGTGGAGGAGGTGAAGGACCAGTTCGCCACCCACGAGGCCTTCATGA TGGAGCTGACCGCCCACCAGTCCTCCGTGGGCTCCGTGCTGCAGGCCGGCAACCAGCTGATCACCCAG GGCACCCTGTCCGACGAGGAGGAGTTCGAGATCCAGGAGCAGATGACCCTGCTGAACGCCAGGTGGGA GGCCCTGAGGGTGGAGTCCATGGACAGGCAGTCCAGGCTGCAC

[0257] In some embodiments of any of the aspects, the portion of the nucleic acid encoding the utrophin SLR1 domain comprises the codon-optimized sequence of SEQ ID NO: 428, or a sequence having at least 70%, at least 75%. at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, or at least 99% sequence identity to SEQ ID NO: 428. In some embodiments of any of the aspects, the portion of the nucleic acid encoding the utrophin SLR1 domain comprises the codon-optimized sequence of SEQ ID NO: 428.

[0258] SEQ ID NO: 428 Codon-optimized sequence encoding utrophin SLR1 domainGACTCCTACCAGATCGCCCTGGAGGAGGTGCTGACCTGGCTGCTGTCCGCCGAGGACACCTTCCAGGA GCAGGACGACATCTCCGACGACGTGGAGGAGGTGAAGGACCAGTTCGCCACCCACGAGGCCTTCATGA TGGAGCTGACCGCCCACCAGTCCTCCGTGGGCTCCGTGCTGCAGGCCGGCAACCAGCTGATCACCCAG GGCACCCTGTCCGACGAGGAGGAGTTCGAGATCCAGGAGCAGATGACCCTGCTGAACGCCAGGTGGGA GGCCCTGAGGGTGGAGTCCATGGACAGGCAGTCCAGGCTGCAC

[0259] In some embodiments of any of the aspects, the portion of the nucleic acid encoding the utrophin SLR1 domain comprises the codon-optimized sequence of SEQ ID NO: 430, or a sequence having at least 70%, at least 75%. at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, or at least 99% sequence identity’ to SEQ ID NO: 430. In some embodiments of any of the aspects, the portion of the nucleic acid encoding the utrophin SLR1 domain comprises the codon-optimizcd sequence of SEQ ID NO: 430.

[0260] SEQ ID NO: 430 Codon-optimized sequence encoding utrophin SLR1 domainGATAGCTATCAGATTGCTTTGGAGGAAGTGCTGACCTGGTTGCTTTCTGCAGAAGACACTTTCCAGGA GCAGGATGACATTTCTGATGATGTTGAAGAAGTCAAAGACCAGTTTGCCACCCATGAGGCATTTATGATGGAACTGACTGCCCACCAGTCCTCTGTGGGCTCTGTGCTGCAGGCAGGCAACCAACTGATAACTCAA GGAACACTGTCAGATGAAGAAGAATTTGAGATTCAGGAACAGATGACACTGCTGAATGCTAGATGGGA GGCCCTTAGGGTGGAGAGCATGGACAGGCAGTCCAGGCTGCAT

[0261] In some embodiments of any of the aspects, the portion of the nucleic acid encoding the utrophin SLR1 domain comprises the codon-optimized sequence of SEQ ID NO: 431. or a sequence having at least 70%. at least 75%, at least 80%, at least 85%. at least 90%, at least 95%, at least 98%. or at least 99% sequence identity to SEQ ID NO: 431. In some embodiments of any of the aspects, the portion of the nucleic acid encoding the utrophin SLR1 domain comprises the codon-optimized sequence of SEQ ID NO: 431.

[0262] SEQ ID NO: 431 Codon-optimized sequence encoding utrophin SLR1 domainGACAGCTATCAGATTGCATTGGAGGAAGTGCTGACCTGGTTGCTTTCTGCTGAGGACACTTTCCAGGA GCAGGATGATATTTCTGATGATGTGGAGGAAGTCAAAGACCAGTTTGCTACCCATGAGGCATTTATGA TGGAACTGACTGCACACCAGTCTTCTGTTGGGTCAGTGCTGCAGGCAGGTAACCAACTGATAACTCAA GGAACTCTGTCTGATGAAGAAGAATTTGAGATTCAGGAACAGATGACACTGCTGAATGCCAGATGGGA GGCTCTTAGGGTGGAGAGCATGGACAGGCAGTCCAGGCTGCAT

[0263] In some embodiments of any of the aspects, the portion of the nucleic acid encoding the utrophin SLR1 domain comprises the codon-optimized sequence of SEQ ID NO: 432, or a sequence having at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, or at least 99% sequence identity to SEQ ID NO: 432. In some embodiments of any of the aspects, the portion of the nucleic acid encoding the utrophin SLR1 domain comprises the codon-optimized sequence of SEQ ID NO: 432.

[0264] SEQ ID NO: 432 Codon-optimized sequence encoding utrophin SLR1 domainGATAGCTATCAGATAGCATTGGAGGAAGTGCTGACCTGGTTGCTTTCAGCTGAGGACACTTTCCAGGA GCAGGATGATATTTCTGATGATGTGGAGGAAGTCAAAGACCAGTTTGCCACCCATGAGGCATTTATGA TGGAACTGACTGCTCACCAGTCCAGTGTGGGCTCTGTTCTGCAGGCAGGGAACCAACTGATAACTCAA GGAACACTGTCTGATGAGGAAGAATTTGAGATTCAGGAACAGATGACTCTGCTGAATGCCAGATGGGA GGCCCTTAGGGTAGAGAGCATGGACAGGCAGTCCAGACTGCAT

[0265] In some embodiments of any of the aspects, the portion of the nucleic acid encoding the utrophin SLR1 domain comprises the codon-optimized sequence of SEQ ID NO: 434. or a sequence having at least 70%. at least 75%, at least 80%, at least 85%. at least 90%, at least 95%, at least 98%. or at least 99% sequence identity to SEQ ID NO: 434. In some embodiments of any of the aspects, the portion of the nucleic acid encoding the utrophin SLR1 domain comprises the codon-optimized sequence of SEQ ID NO: 434.

[0266] SEQ ID NO: 434 Codon-optimized sequence encoding utrophin SLR1 domainGACAGCTATCAGATTGCCTTGGAGGAAGTGCTGACCTGGTTGCTTTCAGCTGAGGACACTTTCCAGGA GCAGGATGACATTTCTGATGATGTTGAAGAAGTCAAAGACCAGTTTGCCACCCATGAAGCCTTTATGA TGGAACTGACTGCACACCAGTCCAGTGTAGGCTCTGTCCTGCAGGCTGGCAACCAACTGATAACCCAA GGAACCCTGTCTGATGAAGAAGAATTTGAGATTCAGGAACAGATGACTCTGCTGAATGCTAGATGGGA GGCACTTAGGGTGGAGAGTATGGACAGGCAGTCCAGACTGCAT

[0267] In some embodiments of any of the aspects, the portion of the nucleic acid encoding the utrophin SLR1 domain comprises the codon-optimized sequence of SEQ ID NO: 435. or a sequence having at least 70%. at least 75%, at least 80%, at least 85%. at least 90%, at least 95%, at least 98%. or at least 99% sequence identity to SEQ ID NO: 435. In some embodiments of any of the aspects, the portion of the nucleic acid encoding the utrophin SLR1 domain comprises the codon-optimized sequence of SEQ ID NO: 435.

[0268] SEQ ID NO: 435 Codon-optimized sequence encoding utrophin SLR1 domainGACAGCTATCAGATTGCTTTGGAGGAAGTGCTGACCTGGTTGCTTAGTGCAGAAGACACCTTCCAGGA GCAGGATGATATTTCAGATGATGTGGAAGAAGTCAAAGACCAGTTTGCCACCCATGAGGCTTTTATGA TGGAACTGACTGCACACCAGAGCTCTGTGGGCAGTGTCCTGCAGGCTGGCAACCAACTGATAACACAA GGAACTCTGTCAGATGAGGAAGAATTTGAGATTCAGGAACAGATGACACTGCTGAATGCTAGATGGGA GGCTCTTAGGGT GGAGAGTAT GGACAGGCAGT CCAGACT GCAT

[0269] In some embodiments of any of the aspects, the portion of the nucleic acid encoding the utrophin SLR1 domain comprises the codon-optimized sequence of SEQ ID NO: 436. or a sequence having at least 70%. at least 75%, at least 80%, at least 85%. at least 90%, at least 95%, at least 98%. or at least 99% sequence identity to SEQ ID NO: 436. In some embodiments of any of the aspects, the portion of the nucleic acid encoding the utrophin SLR1 domain comprises the codon-optimized sequence of SEQ ID NO: 436.

[0270] SEQ ID NO: 436 Codon-optimized sequence encoding utrophin SLR1 domainGACAGTTATCAGATTGCTCTGGAGGAAGTGCTGACCTGGTTGCTTTCAGCTGAAGACACTTTCCAGGA GCAGGATGACATTTCTGATGATGTGGAGGAAGTCAAAGACCAGTTTGCAACTCATGAGGCTTTTATGA TGGAACTGACTGCTCACCAGAGCAGTGTGGGCAGTGTGCTGCAGGCAGGCAACCAACTGATAACCCAA GGAACTCTGAGTGATGAAGAAGAATTTGAGATTCAGGAACAGATGACTCTGCTGAATGCCAGATGGGA GGCTCTTAGGGTGGAGAGTATGGACAGGCAGTCAAGACTGCAT

[0271] In some embodiments of any of the aspects, the portion of the nucleic acid encoding the utrophin SLR1 domain comprises the codon-optimized sequence of SEQ ID NO: 437, or a sequence having at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, or at least 99% sequence identity to SEQ ID NO: 437. In some embodiments of any of the aspects, the portion of the nucleic acid encoding the utrophin SLR1 domain comprises the codon-optimized sequence of SEQ ID NO: 437.

[0272] SEQ ID NO: 437 Codon-optimized sequence encoding utrophin SLR1 domainGACTCTTATCAGATTGCACTGGAGGAAGTGCTGACCTGGTTGCTTTCTGCAGAGGACACTTTCCAGGA GCAGGATGACATTTCTGATGATGTTGAGGAAGTCAAAGACCAGTTTGCTACCCATGAGGCTTTTATGA TGGAACTGACTGCTCACCAGAGCAGTGTGGGCAGTGTGCTGCAGGCAGGCAACCAACTGATAACCCAA GGAACTCTGTCAGATGAAGAAGAATTTGAGATTCAGGAACAGATGACTCTGCTGAATGCTAGATGGGA GGCTCTTAGGGTGGAGAGTATGGACAGACAGAGTAGGCTGCAT

[0273] In some embodiments of any of the aspects, the portion of the nucleic acid encoding the utrophin SLR1 domain comprises the codon-optimized sequence of SEQ ID NO: 438, or a sequence having at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, or at least 99% sequence identity to SEQ ID NO: 438. In some embodiments of any of the aspects, the portion of the nucleic acid encoding the utrophin SLR1 domain comprises the codon-optimized sequence of SEQ ID NO: 438.

[0274] SEQ ID NO: 438 Codon-optimized sequence encoding utrophin SLR1 domainGACTCATATCAGATTGCCCTGGAGGAAGTGCTGACCTGGTTGCTTAGTGCAGAGGACACTTTCCAGGA GCAGGATGACATTAGTGATGATGTGGAAGAAGTCAAAGACCAGTTTGCCACCCATGAGGCTTTTATGA TGGAACTGACTGCCCACCAGAGCAGTGTGGGCTCTGTTCTGCAGGCTGGCAACCAACTGATAACCCAA GGAAC CT GT CAGAT GAAGAAGAATTT GAAAT CAGGAACAGA GACACT GCT GAAT GCAAGA GGGA GGCTCTTAGGGTGGAGAGTATGGACAGACAGTCTAGGCTGCAT

[0275] In some embodiments of any of the aspects, the portion of the nucleic acid encoding the utrophin SLR2 domain comprises a codon-optimized sequence selected from one of SEQ ID NOs: 439-450, or a sequence having at least 70%. at least 75%, at least 80%. at least 85%, at least 90%, at least 95%, at least 98%, or at least 99% sequence identity to one of the foregoing sequences.

[0276] In some embodiments of any of the aspects, the portion of the nucleic acid encoding the utrophin SLR2 domain comprises the codon-optimized sequence of SEQ ID NO: 439, or a sequence having at least 70%, at least 75%. at least 80%. at least 85%, at least 90%. at least 95%, at least 98%, or at least 99% sequence identity to SEQ ID NO: 439. In some embodiments of any of the aspects, the portion of the nucleic acid encoding the utrophin SLR2 domain comprises the codon-optimized sequence of SEQ ID NO: 439.

[0277] SEQ ID NO: 439 Codon-optimized sequence encoding utrophin SLR2 domainGAGCTGCAGAAGAAGCAGCTGCAGCAGCTGTCCGCCTGGCTGACCCTGACCGAGGAGCGCATCCAGAA GATGGAGACCTGCCCCCTGGACGACGACGTGAAGTCCCTGCAGAAGCTGCTGGAGGAGCACAAGTCCC TGCAGTCCGACCTGGAGGCCGAGCAGGTGAAGGTGAACTCCCTGACCCACATGGTGGTGATCGTGGAC GAGAACTCCGGCGAGTCCGCCACCGCCATCCTGGAGGACCAGCTGCAGAAGCTGGGCGAGCGCTGGAC CGCCGTGTGCCGCTGGACCGAGGAGCGCTGGAACCGCCTGCAG

[0278] In some embodiments of any of the aspects, the portion of the nucleic acid encoding the utrophin SLR2 domain comprises the codon-optimized sequence of SEQ ID NO: 440, or a sequence having at least 70%, at least 75%. at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, or at least 99% sequence identity’ to SEQ ID NO: 440. In some embodiments of any of the aspects, the portion of the nucleic acid encoding the utrophin SLR2 domain comprises the codon-optimized sequence of SEQ ID NO: 440.

[0279] SEQ ID NO: 440 Codon-optimized sequence encoding utrophin SLR2 domainGAGCTGCAGAAGAAGCAGCTGCAGCAGCTGAGCGCCTGGCTGACCCTGACCGAGGAGCGGATCCAGAA GATGGAGACCTGCCCCCTGGACGACGACGTGAAGAGCCTGCAGAAGCTGCTGGAGGAGCACAAGAGCC TGCAGAGCGACCTGGAGGCCGAGCAGGTGAAGGTGAACAGCCTGACCCACATGGTGGTGATCGTGGAC GAGAACAGCGGCGAGAGCGCCACCGCCATCCTGGAGGACCAGCTGCAGAAGCTGGGCGAGCGGTGGAC CGCCGTGTGCCGGTGGACCGAGGAGCGGTGGAACCGGCTGCAG

[0280] In some embodiments of any of the aspects, the portion of the nucleic acid encoding the utrophin SLR2 domain comprises the codon-optimized sequence of SEQ ID NO: 441. or a sequence having at least 70%. at least 75%, at least 80%, at least 85%. at least 90%, at least 95%, at least 98%. or at least 99% sequence identity to SEQ ID NO: 441. In some embodiments of any of the aspects, the portion of the nucleic acid encoding the utrophin SLR2 domain comprises the codon-optimized sequence of SEQ ID NO: 441.

[0281] SEQ ID NO: 441 Codon-optimized sequence encoding utrophin SLR2 domainGAGCTGCAGAAGAAGCAGCTGCAGCAGCTGTCCGCCTGGCTGACCCTGACCGAGGAGAGGATCCAGAA GATGGAGACCTGCCCTCTGGACGACGACGTGAAGTCCCTGCAGAAGCTGCTGGAGGAGCACAAGTCCC TGCAGTCCGACCTGGAGGCCGAGCAGGTGAAGGTGAACTCCCTGACCCACATGGTGGTGATCGTGGAC GAGAACTCCGGCGAGTCCGCCACCGCCATCCTGGAGGACCAGCTGCAGAAGCTGGGCGAGAGGTGGAC CGCCGTGTGCAGGTGGACCGAGGAGAGGTGGAACAGGCTGCAG

[0282] In some embodiments of any of the aspects, the portion of the nucleic acid encoding the utrophin SLR2 domain comprises the codon-optimized sequence of SEQ ID NO: 442, or a sequence having at least 70%, at least 75%. at least 80%, at least 85%, at least 90%. at least 95%, at least 98%, or at least 99% sequence identity to SEQ ID NO: 442. In some embodiments of any of the aspects, the portion of the nucleic acid encoding the utrophin SLR2 domain comprises the codon-optimized sequence of SEQ ID NO: 442.

[0283] SEQ ID NO: 442 Codon-optimized sequence encoding utrophin SLR2 domainGAGCTGCAGAAGAAGCAGCTGCAGCAGCTGTCCGCCTGGCTGACCCTGACCGAGGAGAGGATCCAGAA GATGGAGACCTGCCCCCTGGACGACGACGTGAAGTCCCTGCAGAAGCTGCTGGAGGAGCACAAGTCCC TGCAGTCCGACCTGGAGGCCGAGCAGGTGAAGGTGAACTCCCTGACCCACATGGTGGTGATCGTGGAC GAGAACTCCGGCGAGTCCGCCACCGCCATCCTGGAGGACCAGCTGCAGAAGCTGGGCGAGAGGTGGAC CGCCGTGTGCAGGTGGACCGAGGAGAGGTGGAACAGGCTGCAG

[0284] In some embodiments of any of the aspects, the portion of the nucleic acid encoding the utrophin SLR2 domain comprises the codon-optimized sequence of SEQ ID NO: 443, or a sequence having at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, or at least 99% sequence identity to SEQ ID NO: 443. In some embodiments of any of the aspects, the portion of the nucleic acid encoding the utrophin SLR2 domain comprises the codon-optimized sequence of SEQ ID NO: 443.

[0285] SEQ ID NO: 443 Codon-optimized sequence encoding utrophin SLR2 domainGAACTGCAGAAGAAGCAACTGCAGCAGCTCTCTGCATGGTTAACACTCACTGAGGAGAGGATTCAGAA GAT G GAAAC T T GC C C C C T GGAT GAT GAT G C AAAT C T C T AC AAAAGC T GC T AGAAGAACA AAAAGT T TGCAATCTGACCTTGAGGCTGAACAGGTGAAAGTAAATTCACTAACTCACATGGTGGTGATTGTGGAT GAGAACAGTGGTGAGAGTGCTACTGCTATCCTAGAAGACCAGTTACAGAAACTTGGAGAGAGGTGGAC AGCAGT AT GCAGGT GGACTGAGGAAAGGT GGAAT AGAT TACAA

[0286] In some embodiments of any of the aspects, the portion of the nucleic acid encoding the utrophin SLR2 domain comprises the codon-optimized sequence of SEQ ID NO: 444. or a sequence having at least 70%. at least 75%, at least 80%, at least 85%. at least 90%, at least 95%, at least 98%.or at least 99% sequence identity to SEQ ID NO: 444. In some embodiments of any of the aspects, the portion of the nucleic acid encoding the utrophin SLR2 domain comprises the codon-optimized sequence of SEQ ID NO: 444.

[0287] SEQ ID NO: 444 Codon-optimized sequence encoding utrophin SLR2 domainGAACTGCAGAAGAAGCAACTGCAGCAGCTCTCTGCCTGGTTAACACTCACAGAGGAGAGGATTCAGAA GAT G GAAAC T T GC C C C C T GGAT GAT GAT GT AAAAT C T C T AC AAAAGC T GC T AGAAGAACAT AAAAGT T T GCAAAGT GATCT T GAGGCT GAACAGGTGAAAGT AAAT TCACT AACT CACATGGT GGT CAT AGT T GAT GAGAACTCAGGTGAGAGTGCCACAGCTATCCTAGAAGACCAGTTACAGAAACTGGGTGAGAGATGGAC TGCAGTCTGCAGGTGGACAGAAGAAAGGTGGAATAGGTTACAA

[0288] In some embodiments of any of the aspects, the portion of the nucleic acid encoding the utrophin SLR2 domain comprises the codon-optimized sequence of SEQ ID NO: 445, or a sequence having at least 70%, at least 75%. at least 80%, at least 85%, at least 90%. at least 95%, at least 98%, or at least 99% sequence identity to SEQ ID NO: 445. In some embodiments of any of the aspects, the portion of the nucleic acid encoding the utrophin SLR2 domain comprises the codon-optimized sequence of SEQ ID NO: 445.

[0289] SEQ ID NO: 445 Codon-optimized sequence encoding utrophin SLR2 domainGAACTGCAGAAGAAGCAACT GCAGCAGCT CT CT GCT T GGT T AACACT CACAGAGGAGAGGAT T CAGAA GAT G GAAAC T T GC C C C C T GGAT GAT GAT GT AAAAT C T C T AC AAAAGC T GC T AGAAGAACAT AAAAGT T T GCAAAGT GACCT T GAGGCAGAGCAGGTGAAAGT AAAT TCACT AACT CACATGGT GGT CAT T GT T GAT GAAAACTCAGGGGAGTCAGCTACAGCTATCCTAGAAGACCAGTTACAGAAATTGGGTGAGAGGTGGAC AGCTGTATGCAGGTGGACTGAGGAAAGGTGGAATAGGTTACAA

[0290] In some embodiments of any of the aspects, the portion of the nucleic acid encoding the utrophin SLR2 domain comprises the codon-optimized sequence of SEQ ID NO: 446, or a sequence having at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, or at least 99% sequence identity to SEQ ID NO: 446. In some embodiments of any of the aspects, the portion of the nucleic acid encoding the utrophin SLR2 domain comprises the codon-optimized sequence of SEQ ID NO: 446.

[0291] SEQ ID NO: 446 Codon-optimized sequence encoding utrophin SLR2 domainGAACTGCAGAAGAAGCAACT GCAGCAGCT CT CAGCAT GGT T AACACT CACAGAGGAGAGGAT T CAGAA GAT G GAAAC T T GC C C C C T GGAT GAT GAT GT GAAAT C T C TAG AAAAGC T GC T AGAAGAACAT AAAAGT T T GCAAT CAGATCT T GAGGCT GAACAGGTGAAAGT AAAT TCACT AACT CACATGGT GGT GAT T GT GGAT GAGAACTCAGGGGAGAGTGCTACAGCAATCCTAGAAGACCAGTTACAGAAACTGGGGGAGAGATGGAC AGCAGT CT GCAGGT GGACAGAGGAAAGAT GGAAT AGGT TACAA

[0292] In some embodiments of any of the aspects, the portion of the nucleic acid encoding the utrophin SLR2 domain comprises the codon-optimized sequence of SEQ ID NO: 447, or a sequence having at least 70%, at least 75%, at least 80%, at least 85%. at least 90%, at least 95%, at least 98%. or at least 99% sequence identity to SEQ ID NO: 447. In some embodiments of any of the aspects, the portion of the nucleic acid encoding the utrophin SLR2 domain comprises the codon-optimized sequence of SEQ ID NO: 447.

[0293] SEQ ID NO: 447 Codon-optimized sequence encoding utrophin SLR2 domainGAACTGCAGAAGAAGCAACTGCAGCAGCTCTCAGCCTGGTTAACACTCACAGAGGAGAGAATTCAGAA GATGGAAACCTGCCCACTGGATGATGATGTGAAATCTCTACAAAAGCTGCTAGAAGAACATAAAAGTT T GCAAT CT GACCT T GAGGCT GAACAGGTGAAAGT AAAT TCACT AACT CACATGGT GGT CAT T GT AGAT GAGAACAGT GGGGAGAGTGCCACAGCT AT CCTAGAAGACCAGT T ACAGAAACT T GGGGAGAGAT GGAC TGCAGTGTGCAGGTGGACTGAGGAAAGGTGGAATAGATTACAA

[0294] In some embodiments of any of the aspects, the portion of the nucleic acid encoding the utrophin SLR2 domain comprises the codon-optimized sequence of SEQ ID NO: 448, or a sequence having at least 70%, at least 75%. at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, or at least 99% sequence identity’ to SEQ ID NO: 448. In some embodiments of any of the aspects, the portion of the nucleic acid encoding the utrophin SLR2 domain comprises the codon-optimized sequence of SEQ ID NO: 448.

[0295] SEQ ID NO: 448 Codon-optimized sequence encoding utrophin SLR2 domainGAACTGCAGAAGAAGCAACTGCAGCAGCTCTCAGCCTGGTTAACACTCACTGAGGAGAGGATTCAGAA GAT G GAAAC C T GC C C T C T GGAT GAT GAT GT C AAAT C T C T AC AAAAGC T GC T AGAAGAACAT AAAAGT T TGCAATCTGATCTTGAGGCTGAACAGGTGAAAGTAAATTCACTAACTCACATGGTGGTGATTGTTGAT GAAAACAGT GGAGAGAGTGCAACAGCT AT CCTAGAAGACCAGT ACAGAAACT T GGT GAGAGGT GGAC TGCAGTGTGCAGAT GGACAGAAGAAAGAT GGAATAGGT T ACAA

[0296] In some embodiments of any of the aspects, the portion of the nucleic acid encoding the utrophin SLR2 domain comprises the codon-optimized sequence of SEQ ID NO: 449, or a sequence having at least 70%, at least 75%. at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, or at least 99% sequence identity to SEQ ID NO: 449. In some embodiments of any of the aspects, the portion of the nucleic acid encoding the utrophin SLR2 domain comprises the codon-optimized sequence of SEQ ID NO: 449.

[0297] SEQ ID NO: 449 Codon-optimized sequence encoding utrophin SLR2 domainGAACTGCAGAAGAAGCAACT GCAGCAGCT CAGT GCT T GGT T AACACT CACAGAGGAGAGAAT T CAGAA GAT G GAAAC C T GC C C C C T GGAT GAT GAT GT C AAAT C T C TAG AAAAGC T GC T AGAAGAACAT AAAAGT T T GCAAT CAGATCT T GAGGCT GAGCAGGTGAAAGT AAAT TCACT AACT CACATGGT GGT CAT T GT T GAT GAAAACAGTGGTGAGAGTGCTACAGCCATCCTAGAAGACCAGTTACAGAAACTTGGAGAGAGGTGGAC T GCAGT AT GCAGAT GGACAGAAGAAAGAT GGAATAGGT TACAA

[0298] In some embodiments of any of the aspects, the portion of the nucleic acid encoding the utrophin SLR2 domain comprises the codon-optimized sequence of SEQ ID NO: 450, or a sequence having at least 70%, at least 75%. at least 80%, at least 85%, at least 90%. at least 95%, at least 98%, or at least 99% sequence identity to SEQ ID NO: 450. In some embodiments of any of the aspects, the portion of the nucleic acid encoding the utrophin SLR2 domain comprises the codon-optimized sequence of SEQ ID NO: 450.

[0299] SEQ ID NO: 450 Codon-optimized sequence encoding utrophin SLR2 domainGAACTGCAGAAGAAGCAACTGCAGCAGCTCTCAGCCTGGTTAACACTCACAGAGGAGAGAATTCAGAA GATGGAAACATGCCCACTGGATGATGATGTGAAATCTCTACAAAAGCTGCTAGAAGAACATAAAAGTT T GCAAT CAGATCT T GAGGCT GAGCAGGTGAAAGT AAAT TCACT AACT CACATGGT GGT TAT T GT GGAT GAAAACT CAGGTGAAT CAGCAACAGC AT CCTAGAAGACCAGT T ACAGAAACT T GGAGAGAGGT GGAC AGCT GT AT GCAGGT GGACTGAAGAAAGGT GGAAT AGAT TACAA

[0300] In some embodiments of any of the aspects, the portion of the nucleic acid encoding the utrophin SLR3 domain comprises a codon-optimized sequence selected from one of SEQ ID NOs: 451-462, or a sequence having at least 70%, at least 75%, at least 80%, at least 85%. at least 90%, at least 95%, at least 98%, or at least 99% sequence identity to one of the foregoing sequences.

[0301] In some embodiments of any of the aspects, the portion of the nucleic acid encoding the utrophin SLR3 domain comprises the codon-optimized sequence of SEQ ID NO: 451, or a sequence having at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, or at least 99% sequence identity to SEQ ID NO: 451. In some embodiments of any of the aspects, the portion of the nucleic acid encoding the utrophin SLR3 domain comprises the codon-optimized sequence of SEQ ID NO: 451.

[0302] SEQ ID NO: 451 Codon-optimized sequence encoding utrophin SLR3 domainCAGGAGCTGCTGGAGGAGCAGTGCCTGCTGAAGGCCTGGCTGACCGAGAAGGAGGAGGCCCTGAACAA GGTGCAGACCTCCAACTTCAAGGACCAGAAGGAGCTGTCCGTGTCCGTGCGCCGCCTGGCCATCCTGA AGGAGGACATGGAGATGAAGCGCCAGACCCTGGACCAGCTGTCCGAGATCGGCCAGGACGTGGGCCAG CTGCTGGACAACTCCAAGGCCTCCAAGAAGATCAACTCCGACTCCGAGGAGCTGACCCAGCGCTGGGA CTCCCTGGTGCAGCGCCTGGAGGACTCCTCCAACCAGGTGACC

[0303] In some embodiments of any of the aspects, the portion of the nucleic acid encoding the utrophin SLR3 domain comprises the codon-optimized sequence of SEQ ID NO: 452, or a sequence having at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, or at least 99% sequence identity to SEQ ID NO: 452. In some embodiments of any of the aspects, the portion of the nucleic acid encoding the utrophin SLR3 domain comprises the codon-optimized sequence of SEQ ID NO: 452.

[0304] SEQ ID NO: 452 Codon-optimized sequence encoding utrophin SLR3 domainCAGGAGCTGCTGGAGGAGCAGTGCCTGCTGAAGGCCTGGCTGACCGAGAAGGAGGAGGCCCTGAACAA GGTGCAGACCAGCAACTTCAAGGACCAGAAGGAGCTGAGCGTGAGCGTGCGGCGGCTGGCCATCCTGA AGGAGGACATGGAGATGAAGCGGCAGACCCTGGACCAGCTGAGCGAGATCGGCCAGGACGTGGGCCAG CTGCTGGACAACAGCAAGGCCAGCAAGAAGATCAACAGCGACAGCGAGGAGCTGACCCAGCGGTGGGA CAGCCTGGTGCAGCGGCTGGAGGACAGCAGCAACCAGGTGACC

[0305] In some embodiments of any of the aspects, the portion of the nucleic acid encoding the utrophin SLR3 domain comprises the codon-optimized sequence of SEQ ID NO: 453, or a sequence having at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, or at least 99% sequence identity to SEQ ID NO: 453. In some embodiments of any of the aspects, theportion of the nucleic acid encoding the utrophin SLR3 domain comprises the codon-optimized sequence of SEQ ID NO: 453.

[0306] SEQ ID NO: 453 Codon-optimized sequence encoding utrophin SLR3 domainCAGGAGCTGCTGGAGGAGCAGTGCCTGCTGAAGGCCTGGCTGACCGAGAAGGAGGAGGCCCTGAACAA GGTGCAGACCTCCAACTTCAAGGACCAGAAGGAGCTGTCCGTGTCCGTGAGGAGGCTGGCCATCCTGA AGGAGGACATGGAGATGAAGAGGCAGACCCTGGACCAGCTGTCCGAGATCGGCCAGGACGTGGGCCAG CTGCTGGACAACTCCAAGGCCTCCAAGAAGATCAACTCCGACTCCGAGGAGCTGACCCAGAGGTGGGA CTCCCTGGTGCAGAGGCTGGAGGACTCCTCCAACCAGGTGACC

[0307] In some embodiments of any of the aspects, the portion of the nucleic acid encoding the utrophin SLR3 domain comprises the codon-optimized sequence of SEQ ID NO: 454, or a sequence having at least 70%, at least 75%. at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, or at least 99% sequence identity to SEQ ID NO: 454. In some embodiments of any of the aspects, the portion of the nucleic acid encoding the utrophin SLR3 domain comprises the codon-optimized sequence of SEQ ID NO: 454.

[0308] SEQ ID NO: 454 Codon-optimized sequence encoding utrophin SLR3 domainCAGGAGCTGCTGGAGGAGCAGTGCCTGCTGAAGGCCTGGCTGACCGAGAAGGAGGAGGCCCTGAACAA GGTGCAGACCTCCAACTTCAAGGACCAGAAGGAGCTGTCCGTGTCCGTGAGGAGGCTGGCCATCCTGA AGGAGGACATGGAGATGAAGAGGCAGACCCTGGACCAGCTGTCCGAGATCGGCCAGGACGTGGGCCAG CTGCTGGACAACTCCAAGGCCTCCAAGAAGATCAACTCCGACTCCGAGGAGCTGACCCAGAGGTGGGA CTCCCTGGTGCAGAGGCTGGAGGACTCCTCCAACCAGGTGACC

[0309] In some embodiments of any of the aspects, the portion of the nucleic acid encoding the utrophin SLR3 domain comprises the codon-optimized sequence of SEQ ID NO: 455, or a sequence having at least 70%, at least 75%. at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, or at least 99% sequence identity to SEQ ID NO: 455. In some embodiments of any of the aspects, the portion of the nucleic acid encoding the utrophin SLR3 domain comprises the codon-optimized sequence of SEQ ID NO: 455.

[0310] SEQ ID NO: 455 Codon-optimized sequence encoding utrophin SLR3 domainCAGGAATTATTGGAAGAACAGTGCTTGTTGAAAGCCTGGTTAACTGAAAAAGAAGAGGCTTTAAATAA AGTCCAGACATCCAACTTCAAAGACCAAAAGGAACTAAGTGTGAGTGTAAGAAGGCTGGCTATTTTGA AGGAAGACAT GGAAAT GAAGAGGCAAACAT T GGATCAGCT GAGT GAGAT AGGT CAGGATGT GGGACAA TTACTTGATAATTCCAAGGCTTCTAAGAAGATCAACTCAGACAGTGAGGAACTGACTCAAAGGTGGGA TTCTTTGGTTCAGAGACTAGAAGATTCCTCCAACCAGGTGACT

[0311] In some embodiments of any of the aspects, the portion of the nucleic acid encoding the utrophin SLR3 domain comprises the codon-optimized sequence of SEQ ID NO: 456, or a sequence having at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, at least 98%. or at least 99% sequence identity to SEQ ID NO: 456. In some embodiments of any of the aspects, the portion of the nucleic acid encoding the utrophin SLR3 domain comprises the codon-optimized sequence of SEQ ID NO: 456.

[0312] SEQ ID NO: 456 Codon-optimized sequence encoding utrophin SLR3 domainCAGGAATTATTGGAAGAACAGTGCTTGTTGAAAGCATGGTTAACTGAAAAAGAAGAGGCTTTAAATAA AGTCCAGACAAGCAACTTCAAAGACCAAAAGGAACTAAGTGTCAGTGTTAGGAGGCTGGCTATTTTGA AGGAAGACAT GGAAAT GAAGAGACAAACAT T GGATCAGCT GAGT GAGAT AGGCCAGGATGT GGGACAA TTACTTGATAATTCCAAGGCCTCTAAGAAGATCAACTCAGATTCAGAGGAACTGACTCAAAGGTGGGA TTCCTTGGTTCAGAGACTAGAAGATTCCTCCAACCAGGTGACT

[0313] In some embodiments of any of the aspects, the portion of the nucleic acid encoding the utrophin SLR3 domain comprises the codon-optimized sequence of SEQ ID NO: 457, or a sequence having at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, or at least 99% sequence identity to SEQ ID NO: 457. In some embodiments of any of the aspects, the portion of the nucleic acid encoding the utrophin SLR3 domain comprises the codon-optimized sequence of SEQ ID NO: 457.

[0314] SEQ ID NO: 457 Codon-optimized sequence encoding utrophin SLR3 domainCAGGAATTATTGGAAGAACAGTGCTTGTTGAAAGCTTGGTTAACAGAGAAAGAAGAGGCTTTAAATAA AGTCCAGACATCCAACTTCAAAGACCAAAAGGAACTAAGTGTATCTGTGAGGAGGCTGGCTATTTTGA AGGAAGACAT GGAAAT GAAGAGACAAACAT T GGATCAGCT GTCAGAGATAGGGCAGGATGT GGGACAA TTACTTGATAATTCCAAGGCATCTAAGAAGATCAACTCAGACTCAGAGGAACTGACTCAAAGGTGGGA TTCCTTGGTTCAGAGACTAGAAGATTCCTCCAACCAGGTGACT

[0315] In some embodiments of any of the aspects, the portion of the nucleic acid encoding the utrophin SLR3 domain comprises the codon-optimized sequence of SEQ ID NO: 458. or a sequence having at least 70%. at least 75%, at least 80%, at least 85%. at least 90%, at least 95%, at least 98%. or at least 99% sequence identity to SEQ ID NO: 458. In some embodiments of any of the aspects, the portion of the nucleic acid encoding the utrophin SLR3 domain comprises the codon-optimized sequence of SEQ ID NO: 458.

[0316] SEQ ID NO: 458 Codon-optimized sequence encoding utrophin SLR3 domainCAGGAATTATTGGAAGAACAGTGCTTGTTGAAAGCTTGGTTAACTGAAAAAGAAGAGGCTTTAAATAA AGTCCAGACAAGCAACTTCAAAGACCAAAAGGAACTATCAGTGTCAGTTAGAAGGCTGGCTATTTTGA AGGAAGACAT GGAAAT GAAGAGGCAAACAT T GGATCAGCT GAGT GAGAT AGGGCAGGATGT GGGGCAA TTACTTGATAATTCCAAGGCATCTAAGAAGATCAACTCTGACTCAGAGGAACTGACTCAAAGGTGGGA TTCTTTGGTTCAGAGACTAGAAGATTCCTCCAACCAGGTGACT

[0317] In some embodiments of any of the aspects, the portion of the nucleic acid encoding the utrophin SLR3 domain comprises the codon-optimized sequence of SEQ ID NO: 459, or a sequence having at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, or at least 99% sequence identity to SEQ ID NO: 459. In some embodiments of any of the aspects, the portion of the nucleic acid encoding the utrophin SLR3 domain comprises the codon-optimized sequence of SEQ ID NO: 459.

[0318] SEQ ID NO: 459 Codon-optimized sequence encoding utrophin SLR3 domainCAGGAATTATTGGAAGAACAGTGCTTGTTGAAAGCTTGGTTAACTGAGAAAGAAGAGGCCTTAAATAA AGTCCAGACTAGCAACTTCAAAGACCAAAAGGAACTAAGTGTGAGTGTTAGGAGGCTGGCTATTTTGA AGGAAGACATGGAAATGAAGAGACAAACTTTGGATCAGCTGAGTGAGATTGGCCAGGATGTAGGGCAATTACTTGACAATTCCAAGGCCTCTAAGAAGATCAACAGTGACTCAGAGGAACTGACTCAAAGATGGGA TTCTCTAGTTCAGAGACTGGAAGATTCCTCCAACCAGGTGACT

[0319] In some embodiments of any of the aspects, the portion of the nucleic acid encoding the utrophin SLR3 domain comprises the codon-optimized sequence of SEQ ID NO: 460, or a sequence having at least 70%, at least 75%, at least 80%, at least 85%, at least 90%, at least 95%, at least 98%, or at least 99% sequence identity to SEQ ID NO: 460. In some embodiments of any of the aspects, the portion of the nucleic acid encoding the utrophin SLR3 domain comprises the codon-optimized sequence of SEQ ID NO: 460.

[0320] SEQ ID NO: 460 Codon-optimized sequence encoding utrophin SLR3 domainCAGGAATTATTGGAAGAACAGTGCTTGTTGAAAGCTTGGTTAACTGAGAAAGAAGAGGCCTTAAATAA AGTCCAGACAAGCAACTTCAAAGACCAAAAGGAACTAAGTGTGTCTGTTAGGAGGCTGGCTATTTTGA AGGAAGACATGGAAATGAAGAGACAAACCTTGGATCAGCTGAGTGAGATTGGGCAGGATGTGGGTCAA TTACTTGATAATTCCAAGGCCTCTAAGAAGATCAACAGTGACTCTGAAGAACTGACTCAAAGATGGGA TTCTCTTGTTCAGAGATTGGAAGATTCCTCCAACCAGGTGACT

[0321] In some embodiments of any of the aspects, the portion of the nucleic acid encoding the utrophin SLR3 domain comprises the codon-optimized sequence of SEQ ID NO: 461. or a sequence having at least 70%. at least 75%, at least 80%, at least 85%. at least 90%, at least 95%, at least 98%. or at le...

Claims

What is claimed herein is:

1. A polypeptide comprising: a) a utrophin NT domain; b) a utrophin hinge 1 domain; c) a utrophin spectrin-like repeat (SLR) 1 domain; d) a utrophin spectrin-like repeat (SLR) 2 domain; e) a utrophin hinge 2 domain; f) a dystrophin SLR 20 domain; g) a dystrophin SLR 21 domain; h) a dystrophin SLR 22 domain; i) a dystrophin SLR 24 domain; j) a dystrophin hinge 4 domain; and k) a dystrophin cysteine rich (CR) domain.

2. The polypeptide of any one of the preceding claims, wherein the polypeptide further comprises a utrophin spectrin-like repeat (SLR) 3 domain.

3. A polypeptide comprising: a utrophin NT domain; a utrophin hinge 1 domain; a utrophin spectrin-like repeat (SLR) 1 domain; a utrophin spectrin-like repeat (SLR) 2 domain; a utrophin hinge 2 domain; a dystrophin SLR 20 domain; a dystrophin SLR 21 domain; a dystrophin SLR 22 domain; a dystrophin SLR 24 domain; a dystrophin hinge 4 domain; and a dystrophin cysteine rich (CR) domain. a utrophin spectrin-like repeat (SLR) 3 domain.

4. The polypeptide of any one of the preceding claims, wherein the polypeptide further comprises a dystrophin SLR 23 domain.

5. The polypeptide of any one of the preceding claims, wherein the polypeptide further comprises a utrophin spectrin-like repeat (SLR) 3 domain and a dystrophin SLR 23 domain.

6. The polypeptide of any one of the preceding claims, wherein the polypeptide further comprises a dystroglycan binding domain.

7. The polypeptide of any one of the preceding claims, wherein the polypeptide further comprises a domain selected from the group consisting of: a utrophin SLR 4 domain, a utrophin SLR 5 domain, a utrophin SLR 6 domain, a utrophin SLR 7 domain, a utrophin SLR 8 domain, a utrophin SLR 9 domain, a utrophin SLR 10 domain, a utrophin SLR 11 domain, a utrophin SLR 12 domain, a utrophin SLR 13 domain, a utrophin SLR 14 domain, a utrophin SLR 15 domain, a utrophin SLR 16 domain, a utrophin SLR 17 domain, and a utrophin hinge 3 domain.

8. The polypeptide of any one of the preceding claims, wherein the polypeptide further comprises a domain selected from the group consisting of: a dystrophin SLR 4 domain, a dystrophin SLR 5 domain, a dystrophin SLR 6 domain, a dystrophin SLR 7 domain, a dystrophin SLR 8 domain, a dystrophin SLR 9 domain, a dystrophin SLR 10 domain, a dystrophin SLR 11 domain, a dystrophin SLR 12 domain, a dystrophin SLR 13 domain, a dystrophin SLR 14 domain, a dystrophin SLR 15 domain, a dystrophin SLR 16 domain, a dystrophin SLR 17 domain, dystrophin SLR 18 domain, and a dystrophin SLR 19 domain.

9. The polypeptide of any one of the preceding claims, wherein the polypeptide comprises, from N- terminus to C-terminus: a) a utrophin NT domain; b) a utrophin hinge 1 domain; c) a utrophin spectrin-like repeat (SLR) 1 domain; d) a utrophin spectrin-like repeat (SLR) 2 domain; e) a utrophin hinge 2 domain; f) a dystrophin SLR 20 domain; g) a dy strophin SLR 21 domain; h) a dy strophin SLR 22 domain; i) a dystrophin SLR 24 domain; j) a dystrophin hinge 4 domain; k) a dystrophin cysteine rich (CR) domain; and l) a dystrogly can binding domain.

10. The polypeptide of any one of the preceding claims, wherein the polypeptide comprises, from N- terminus to C-terminus: a) a utrophin NT domain; b) a utrophin hinge 1 domain; c) a utrophin spectrin-like repeat (SLR) 1 domain; d) a utrophin spectrin-like repeat (SLR) 2 domain;c) a utrophin spcctrin-likc repeat (SLR) 3 domain; f) a utrophin hinge 2 domain; g) a dystrophin SLR 20 domain; h) a dystrophin SLR 21 domain; i) a dystrophin SLR 22 domain; j) a dystrophin SLR 24 domain; k) a dystrophin hinge 4 domain; l) a dystrophin cysteine rich (CR) domain; and m) a dystrogly can binding domain.

11. The polypeptide of any one of the preceding claims, wherein the polypeptide comprises, from N- terminus to C-terminus: a) a utrophin NT domain; b) a utrophin hinge 1 domain; c) a utrophin spectrin-like repeat (SLR) 1 domain; d) a utrophin spectrin-like repeat (SLR) 2 domain; e) a utrophin hinge 2 domain;I) a dystrophin SLR 20 domain; g) a dystrophin SLR 21 domain; h) a dystrophin SLR 22 domain; i) a dystrophin SLR 23 domain; j) a dystrophin SLR 24 domain; k) a dystrophin hinge 4 domain; l) a dystrophin cysteine rich (CR) domain; and m) a dy strogly can binding domain.

12. The polypeptide of any one of the preceding claims, wherein: a) the utrophin NT domain comprises the sequence of SEQ ID NO: 4 or 51 ; b) the utrophin hinge 1 domain comprises the sequence of SEQ ID NO: 5; c) the utrophin SLR 1 domain comprises the sequence of SEQ ID NO: 6; d) the utrophin SLR 2 domain comprises the sequence of SEQ ID NO: 7; e) the utrophin SLR 3 domain comprises the sequence of SEQ ID NO: 16; f) the utrophin hinge 2 domain comprises the sequence of SEQ ID NO: 8; g) the dystrophin SLR 20 domain comprises the sequence of SEQ ID NO: 9 or 500; h) the dystrophin SLR 21 domain comprises the sequence of SEQ ID NO: 10 or 501; i) the dystrophin SLR 22 domain comprises the sequence of SEQ ID NO: 11 or 502; j) the dystrophin SLR 23 domain comprises the sequence of SEQ ID NO: 12; k) the dystrophin SLR 24 domain comprises the sequence of SEQ ID NO: 13 or 503;l) the dystrophin hinge 4 domain comprises the sequence of SEQ ID NO: 14 or 504; m) the dystrophin CR domain comprises the sequence of SEQ ID NO: 15 or 505; n) the dystroglycan binding domain comprises the sequence of SEQ ID NO: 17 or 506 and / or o) sequences having at least 85%, at least 90%, at least 95% or greater sequence identity to any of the foregoing sequences.

13. The polypeptide of any one of the preceding claims, comprising the sequence of one of SEQ ID NOs: 1-3.

14. The polypeptide of any one of the preceding claims, comprising the sequence of SEQ ID NO: 1.

15. The polypeptide of any one of the preceding claims, comprising the sequence of SEQ ID NO: 2.

16. The polypeptide of any one of the preceding claims, comprising the sequence of SEQ ID NO: 3.

17. The polypeptide of any one of the preceding claims, wherein the polypeptide does not comprise any of: a) a dystrophin SLR4 - SLR19 domain; b) a utrophin SLR4-SLR19 domain; c) a dystrophin hinge 3 domain; and d) a utrophin hinge 3 domain.

18. The polypeptide of any one of the preceding claims, wherein the polypeptide does not comprise any of: a) a dystrophin NT domain; b) a dystrophin hinge 1 domain; c) a dystrophin spectrin-like repeat (SLR) 1 domain; and d) a dystrophin spectrin-like repeat (SLR) 2 domain.

19. The polypeptide of any one of the preceding claims, wherein the polypeptide does not comprise any of: a) a dy strophin NT domain; b) a dystrophin hinge 1 domain; c) a dystrophin spectrin-like repeat (SLR) 1 domain; d) a dystrophin spectrin-like repeat (SLR) 2 domain; and e) a dystrophin hinge 3 domain.

20. The polypeptide of any one of the preceding claims, wherein the polypeptide does not comprise any of: a) a dystrophin NT domain; b) a dystrophin hinge 1 domain; c) a dystrophin spectrin-like repeat (SLR) 1 domain; d) a dystrophin spectrin-like repeat (SLR) 2 domain; andc) a dystrophin hinge 2 domain.

21. The polypeptide of any one of the preceding claims, wherein the polypeptide does not comprise any of: a) a dystrophin NT domain; and b) a dystrophin hinge 1 domain.

22. The polypeptide of any one of the preceding claims, wherein the polypeptide does not comprise any of: a) a utrophin SLR 18 domain; b) a utrophin SLR 19 domain; c) a utrophin SLR 20 domain; d) a utrophin SLR 21 domain; e) a utrophin SLR 22 domain; f) a utrophin hinge 4 domain; and g) a utrophin CR domain.

23. A nucleic acid encoding the polypeptide of any one of the preceding claims.

24. The nucleic acid of claim 23, comprising a sequence of one of SEQ ID NOs: 85-87, or a sequence having at least 85%, at least 90%. at least 95% or greater sequence identity to any of the foregoing sequences.

25. The nucleic acid of claim 23, wherein one or more of the regions or domains is encoded by a codon-optimized sequence of one of SEQ ID NOs: 100-111, or a sequence having at least 80%, at least 85%, at least 90%, at least 95%, or greater sequence identity to any of the foregoing sequences.

26. The nucleic acid of any one of claims 23-25, wherein the utrophin NT region, the utrophin SLR domain 1, the utrophin SLR domain 2, and / or the utrophin SLR domain 3 are encoded by a codon- optimized sequence of one of SEQ ID NOs: 400-474, or a sequence having at least 80%, at least 85%, at least 90%, at least 95%, or greater sequence identity to any of the foregoing sequences.

27. The nucleic acid of any one of claims 23-26, wherein the utrophin NT region and the utrophin hinge 2 domain are encoded by a codon-optimized sequence of one of SEQ ID NOs: 400-412 and 463-474, or a sequence having at least 80%, at least 85%, at least 90%, at least 95%, or greater sequence identity' to any of the foregoing sequences.

28. The nucleic acid of any one of claims 23-27, operably connected to a promoter.

29. The nucleic acid of claim 28, wherein the promoter is a muscle-specific promoter.

30. The nucleic acid of claim 29, wherein the muscle-specific promoter is selected from the group consisting of:SP0524; SPc5-12; SP0525; SP0526; SP0527; SP0528; SCP1; and CRE0053.

31. The nucleic acid of claim 29, wherein the muscle-specific promoter is a SP0524 promoter or a SPc5-12 promoter.

32. The nucleic acid of claim 29, wherein the muscle-specific promoter is a SP0524 promoter or a SP0527 promoter.

33. The nucleic acid of claim 29, wherein the muscle-specific promoter is a SP0524 promoter.

34. The nucleic acid of claim 29, wherein the muscle-specific promoter comprises the sequence of one of SEQ ID NOs: 18, 19, 20, 24, 25, 26, 27, 28, 29, or 83.

35. The nucleic acid of claim 29, wherein the muscle-specific promoter comprises the sequence of one of SEQ ID NOs: 18, 20, 24, 25, 26, 27, 28, or 29.

36. The nucleic acid of any one of claims 23-35, flanked by AAV inverted terminal repeats (ITRs).

37. The nucleic acid of any one of claims 23-36, further comprising one or more additional regulatory elements and / or a polyA sequence.

38. The nucleic acid of claim 37, wherein the muscle-specific promoter is a SP0524 promoter and the polyA sequence is the sequence of SEQ ID NO: 52.

39. The nucleic acid of claim 37. wherein the one or more additional regulatory elements is selected from the group consisting of an enhancer, a 5’ untranslated region (5’UTR), an intron, a reverse RNA pol II terminator sequence, and combinations thereof.

40. The nucleic acid of claim 39, wherein the intron is an IVS intron.

41. The nucleic acid of claim 40, wherein the IVS intron comprises a nucleic acid sequence of SEQ ID NO: 22, a nucleic acid having at least 90%, 91%. 92%, 93%, 94%, 95%. 96%, 97%, or 98%, or 99% sequence identity thereto.

42. A vector comprising the nucleic acid sequence of any one of claims 23-41.

43. A vector comprising, from 5’ to 3’: a) a first inverted terminal repeat (ITR); b) a promoter; c) the nucleic acid sequence of claim 18, operably linked to the promoter; d) a poly-A sequence 3’ of the nucleic acid sequence of claim 18; and e) a second ITR.

44. The vector claim of claim 43, wherein the promoter is a muscle-specific promoter.

45. The vector claim of claim 44, wherein the muscle-specific promoter is selected from the group consisting of:SP0524: SPc5-12; SP0525; SP0526; SP0527; SP0528; SCP1; and CRE0053.

46. The vector of claim 44. wherein die muscle-specific promoter is a SP0524 promoter or a SPc5-12 promoter.

47. The vector of claim 44. wherein die muscle-specific promoter comprises the sequence of one of SEQ ID NOs: 18, 19, 20. 24, 25, 26, 27, 28. 29, or 83.

48. The vector of claim 44. wherein die muscle-specific promoter comprises the sequence of one of SEQ ID NOs: 18, 20, 24.

25. 26, 27, 28, or 29.

49. The vector of any one of claims 42-48, wherein the vector is an AAV vector, an adenoviral vector, a retroviral vector, or a lentiviral vector.

50. The vector of claim 49, wherein tire vector is an AAV vector.

51. A recombinant adeno-associated virus (rAAV) vector comprising in its genome the nucleic acid of any one of claims 23-41.

52. A recombinant adeno-associated virus (rAAV) vector comprising in its genome: e) 5‘ and 3’ AAV inverted terminal repeats (ITR) sequences; and f) located between the 5’ and 3’ ITRs, the nucleic acid specified in any one of claims 23-41.

53. The rAAV vector of claims 51-52, wherein the AAV genome further comprises at least one of: i) a 5’ ITR; j) an intron; k) a poly A sequence; and l) a 3’ ITR.

54. The rAAV vector of any one of claims 51-53, wherein the AAV genome comprises, in the 5’ to 3’ direction: c) a 5’ ITR; b) a muscle-specific promoter; c) an intron; d) a nucleic acid specified in any one of claims 23-39; e) a poly A sequence;1) a 3’ ITR.

55. The rAAV vector of any one of claims 51-54, wherein the intron is selected from the group consisting of an IVS sequence, a MVM sequence, a HBB2 sequence, an CMVIE intron sequence, a UBC intron sequence, and a SV40 sequence.

56. The rAAV vector of any one of claims 51-55, wherein at least one of the 5’ ITR or 3’ITR comprises an insertion, deletion or substitution.

57. The rAAV vector of any one of claims 51-56, wherein one or more CpG islands in the ITR are removed.

58. The rAAV vector of any one of claims 51-57, wherein the poly A sequence is a full length SV40 polyA sequence or HGF poly A sequence.

59. The rAAV vector of any one of claims 51-58, wherein poly A sequence is selected from SEQ ID NO: 23 or 52, or a nucleic acid sequence at least 80% sequence identity thereto.

60. The rAAV vector of any one of claims 51-59, wherein the muscle -specific promoter is a SP0524 promoter and the polyA sequence is the sequence of SEQ ID NO: 52.

61. The rAAV vector of any one of claims 51-60, wherein the rAAV vector is a chimeric AAV vector, haploid AAV vector, a hybrid AAV vector or polyploid AAV vector.

62. The rAAV vector of any one of claims 51-61, wherein the rAAV vector is a rational haploid capsid, a mosaic AAV capsid, a chemically modified AAV capsid, or a AAV capsid from any AAV serotypes.

63. -The rAAV vector of any one of claims 51-62. wherein the rAAV capsid is a capsid from an AAV serotype selected from the group consisting of:AAV1, AAV2, AAV3. AAV4, AAV5, AAV6, AAV7. AAV8, AAV9, AAV10, AAV11, AAV12, AAV13, AAVrh74, AAVrhlO, pol, AAV9-PHP.B, AAV9-ePHP.B, AAV LK03, AAV Anc80L65, AAVDJ. AAVlA6ii, AAVlP5ii, AAV4Alii, AAV7P4i, AAV9AH, AAV9A2i, AAV9A6i, AAV9PH, AAV9P21. AAV9P5i, AAVrhlOAli, AAVrhl0A2i, AAVrhlOPli, AAV12P2ii. AAVSIOPli, AAV JEA. AAV2 3xA P2i. AAVDJ P2i, AAV 2i8, AAV2G9, AAV2.5i82g9, AAV2.

5. AAVrl0pLDB_L2, AAVrl0pLDB_P31, AAV4E. AAVMyo, and AAV4A.

64. The rAAV vector of any one of claims 51-63, wherein the rAAV capsid is a capsid from an AAV serotype selected from the group consisting of:AAV9, AAV8. AAVrh74, AAV2i8. and AAVMyo.

65. A pharmaceutical composition comprising the vector of any one of claims 42-64 in a pharmaceutically acceptable carrier.

66. A method of treating Duchenne Muscular Dystrophy (DMD) in a subject in need thereof, the method comprising administering the nucleic acid of any one of claims 23-41. or the vector of any one of claims 42-64, or the composition of claim 65 to the subject.

67. The method of claim 66, wherein the administering is systemic administration.

68. The method of claim 67, wherein the systemic administration is intravenous administration.

69. The method of claim 66, wherein the administering is local administration.

70. The method of claim 69, wherein the local administration is by injection into a muscle.

71. The method of any one of claims 66-70, where the rAAV vector is administered at a dosage range of between 1.0E9 vg / kg to 5.0E14vg / kg72. A vector of any one of claims 42-64, or a nucleic acid of any one of claims 23-41 or composition of claim 65, for use in a method of treating DMD.

73. A polypeptide comprising a utrophin N-terminal portion and a dystrophin C-terminal portion.

74. A polypeptide comprising a dystrophin N-terminal portion and a utrophin C-terminal portion.

75. A microutrophin polypeptide comprising a utrophin NT domain, a utrophin SLR domain 1, a utrophin SLR domain 2, a utrophin SLR domain 3, wherein the microutrophin polypeptide is encoded by a codon optimized nucleic acid sequence.

76. The microutrophin polypeptide of claim 75, further comprising utrophin hinge domain 1, utrophin hinge domain 2, and utrophin hinge domain 4.

77. The microutrophin polypeptide of claim 75, further comprising utrophin SLR domain 22 and utrophin CR domain.

78. The microutrophin polypetide of claim 75, wherein the codon optimized nucleic acid sequence is at least 85% identical to the sequence selected from the group consisting of SEQ ID NOs: 100-111.

79. A nucleic acid encoding the polypeptide of any of the claims 75-78.

80. The nucleic acid of claim 79, operably linked to a muscle specific promoter.

81. The nucleic acid of claim 80, wherein the muscle specific promoter is SP0524; SP0527; or, SPc5- 12.

82. The nucleic acid of claim 80, wherein the muscle-specific promoter comprises the sequence of one of SEQ ID NOs:

18. 19, 20, 24, 25. 26, 27, 28, 29. or 83.

83. The nucleic acid of claim 80. wherein the muscle-specific promoter comprises the sequence of one of SEQ ID NOs: 18, 20, 24, 25, 26, 27, 28, or 29.

84. A recombinant adeno-associated virus (rAAV) vector comprising in its genome the nucleic acid of any one of claims 79-83.

85. The nucleic acid of claim 79-83. or rAAV of claim 84 for use in a method to treat DMD.

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