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

Attorney Docket No: 046192-000119WOPT METHODS AND COMPOSITIONS FOR TREATMENT OF DUCHENNE MUSCULAR DYSTROPHY CROSS-REFERENCE TO RELATED APPLICATIONS

[0001] This application claims benefit under 35 U.S.C. § 119 of U.S. Provisional ApplicationNo.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 submittedelectronically 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 ofDuchenne muscular dystrophy. BACKGROUND

[0004] Duchenne muscular dystrophy (DMD) is a genetic disease caused by mutation(s) of thedystrophin 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. Currenttreatments such as glucocorticoid therapies may slow the progression of DMD, but do not address the underlying lack of dystrophin or muscle injury and degradation.

[0006] In a normal, healthy patient, the utrophin protein is also expressed in muscles. Therelatedness 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 andportions of utrophin to provide a novel chimeric protein provides significantly improved 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;1Attorney Docket No: 046192-000119WOPT 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; andk) 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 adystrophin 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 dystrophin 2Attorney Docket No: 046192-000119WOPT 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.

[0011] In some embodiments of any of the aspects, the polypeptide comprises, from N-terminusto 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; andl) 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;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; andm) 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;3Attorney Docket No: 046192-000119WOPT 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; andm) a dystroglycan 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;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 506and / or o) sequences having at least 85%, at least 90%, at least 95% or greater sequence identityto any of the foregoing sequences.

[0013] In some embodiments of any of the aspects, the polypeptide comprises the sequence ofone 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;4Attorney Docket No: 046192-000119WOPT c) a dystrophin hinge 3 domain; andd) a utrophin hinge 3 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; andd) 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; ande) a dystrophin hinge 3 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; ande) 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; andb) 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; andg) a utrophin CR domain.

[0015] In one aspect of any of the embodiments, described herein is a polypeptide comprising autrophin N-terminal 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-terminal 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 by 5Attorney Docket No: 046192-000119WOPT a 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 isat 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 apolypeptide described herein.

[0018] In some embodiments of any of the aspects, the nucleic acid comprises the sequence ofone 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 apolypeptide 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 muscle- specific 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 muscle- specific 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, 6Attorney Docket No: 046192-000119WOPT the muscle-specific 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 apolypeptide 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 SP0524promoter 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 regulatoryelements 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. In some embodiments of any of the aspects, the intron is an IVS intron. In some embodiments of any of the aspects, 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.

[0023] In one aspect of any of the embodiments, described herein is a vector comprising anucleic 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 asdescribed herein), operably linked to the promoter; d) a poly-A sequence 3’ of the nucleic acid sequence as described herein (e.g., encodinga 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 adenoviralvector, 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; andb) 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;7Attorney Docket No: 046192-000119WOPT b) an intron;c) a poly A sequence; andd) 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; f) a 3’ ITR.

[0026] In some embodiments of any of the aspects, the intron is selected from the groupconsisting 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 SV40polyA 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 serotypes. 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, AAVrh10, po1, AAV9-PHP.B, AAV9-ePHP.B, AAV LK03, AAV Anc80L65, AAVDJ, AAV1A6ii, AAV1P5ii, AAV4A1ii, AAV7P4i, AAV9A1i, AAV9A2i, AAV9A6i, AAV9P1i, AAV9P2i, AAV9P5i, AAVrh10A1i, AAVrh10A2i, AAVrh10P1i, AAV12P2ii, AAVS10P1i, AAV JEA, AAV23xA P2i, AAVDJ P2i, AAV 2i8, AAV2G9, AAV2.5i82g9, AAV2.5, AAVr10pLDB_L2, AAVr10pLDB_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 pharmaceuticalcomposition comprising the vector or rAAV vector as described herein, in a pharmaceutically acceptable carrier. 8Attorney Docket No: 046192-000119WOPT2. In one aspect of any of the embodiments, described herein is a method of treating DuchenneMuscular 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. 1A depicts a schematic of utrophin and dystrophin, reference sequences, andexemplary chimeric sequences described herein. Fig.1B 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 DNA2administration.

[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 DNA6administration.

[0039] Fig. 9 depicts a schematic of µUtrophin construct domains. The µUtrophin schematicdepicts 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.9Attorney Docket No: 046192-000119WOPT

[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 normalizedforce at contraction #50 (Fig.19B) for prior art DNA2.

[0050] Figs. 20A-20B depict graphs of day 20 normalized fatigue (Fig. 20A) and normalizedforce 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 normalizedforce at contraction #50 (Fig.21B) for SI-trophin_09 (DNA4).

[0052] Figs. 22A-22B depict graphs of day 20 normalized fatigue (Fig. 22A) and normalizedforce 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 normalizedforce at contraction #50 (Fig.23B) for prior art DNA6. DETAILED DESCRIPTION

[0054] Aspects of the invention described herein arise from the identification of novel chimericpolypeptides 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 fordelivering 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-limitingexample, that comprise a nucleotide sequence containing inverted terminal 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 the 10Attorney Docket No: 046192-000119WOPT disease, e.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; andk) a dystrophin cysteine rich (CR) domain.

[0058] In some embodiments of any of the aspects, the polypeptide further comprises a utrophinspectrin-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 dystrophinSLR 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 domainselected 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 11Attorney Docket No: 046192-000119WOPT 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 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 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 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 the aspects, the polypeptide 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 13 12Attorney Docket No: 046192-000119WOPT 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.

[0062] In some embodiments of any of the aspects, the polypeptide further comprises a domainselected 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 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 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, a 13Attorney Docket No: 046192-000119WOPT 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 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 toC-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; andk) a dystrophin cysteine rich (CR) 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 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;14Attorney Docket No: 046192-000119WOPT k) a dystrophin hinge 4 domain; andl) a dystrophin cysteine rich (CR) 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 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; andl) a dystrophin cysteine rich (CR) domain.

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

[0065] In some embodiments of any of the aspects, the polypeptide comprises, from N-terminus toC-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; andl) 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;15Attorney Docket No: 046192-000119WOPT 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; andm) 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 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; andm) a dystroglycan binding domain.

[0066] In some embodiments of any of the aspects, the polypeptide consists of, from N-terminus toC-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;16Attorney Docket No: 046192-000119WOPT i) a dystrophin SLR 24 domain;j) a dystrophin hinge 4 domain;k) a dystrophin cysteine rich (CR) domain; andl) 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 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; andm) 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; andm) a dystroglycan binding domain.

[0067] The structures and sequences of utrophin and dystrophin are known in the art, includingthe structures and sequences of the domains of utrophin and dystrophin described herein. For 17Attorney Docket No: 046192-000119WOPT example, the structures of utrophin and dystrophin are described in Blake et 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 sequencewhich 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: 51MAKYGEHEASPDNGQNEFSDIIKSRSDEHNDVQKKTFTKWINARFSKSGKPPINDMFTDLKD GRKLLDLLEGLTGTSLPKERGSTRVHALNNVNRVLQVLHQNNVELVNIGGTDIVDGNHKLT LGLLWSIILHWQVKDVMKDVMSDLQQTNSEKILLSWVRQTTRPYSQVNVLNFTTSWTDGLA FNAVLHRHKPDLFSWDKVVKMSPIERLEHAFSKAQTYLGIEKLLDPEDVAVQLPDKKSIIMY

[0070] In some embodiments of any of the aspects, a utrophin NT domain comprises a sequencewhich 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 ID 18Attorney Docket No: 046192-000119WOPT NO: 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 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 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 LTSLFEVLPQQVTIDAIREVE

[0072] In some embodiments of any of the aspects, a utrophin hinge 1 domain comprises asequence 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 of 19Attorney Docket No: 046192-000119WOPT 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 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 asequence 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, 20Attorney Docket No: 046192-000119WOPT a utrophin 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 asequence 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 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 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 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 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 asequence 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 the 21Attorney Docket No: 046192-000119WOPT aspects, a utrophin 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 asequence 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 ID 22Attorney Docket No: 046192-000119WOPT NO: 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 asequence 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 the 23Attorney Docket No: 046192-000119WOPT sequence 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)FNRAWTELTDWLSLLDQVIKSQRVMVGDLEDINEMIIKQKATMQDLEQRRPQLEELI TAAQNLKNKTSNQEARTIITDRIERIQNQWDEVQEHLQNRRQQLNE

[0084] In some embodiments of any of the aspects, a dystrophin SLR 21 domain comprises asequence 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 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)MLKDSTQWLEAKEEAEQVLGQARAKLESWKEGPYTVDAIQKKITETKQLAKDLRQ WQTNVDVANDLALKLLRDYSADDTRKVHMITENINASWRSIHKRVSEREAALEE

[0086] In some embodiments of any of the aspects, a dystrophin SLR 21 domain comprises asequence which has at least 80% 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 24Attorney Docket No: 046192-000119WOPT least 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 asequence 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 25Attorney Docket No: 046192-000119WOPT 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 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 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 asequence 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 SLR 26Attorney Docket No: 046192-000119WOPT 22 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 asequence 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. In 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 27Attorney Docket No: 046192-000119WOPT

[0094] In some embodiments of any of the aspects, a dystrophin SLR 24 domain comprises asequence 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 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 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 vndlarqltt lgiqlspynl stledlntrw kllqvavedr vrqlhe

[0096] In some embodiments of any of the aspects, a dystrophin SLR 24 domain comprises asequence 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 some 28Attorney Docket No: 046192-000119WOPT 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: 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 asequence 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 the 29Attorney Docket No: 046192-000119WOPT aspects, 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 asequence 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 dystrophin 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)30Attorney Docket No: 046192-000119WOPT AHRDFGPASQHFLSTSVQGPWERAISPNKVPYYINHETQTTCWDHPKMTELYQSLA DLNNVRFSAYRTAMKL

[0102] In some embodiments of any of the aspects, a dystrophin CR domain comprises asequence 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 dystrophin CR domain consists of the sequence of SEQ ID NO: 505.

[0103] Dystrophin CR domain (SEQ ID NO: 505)TSVQGPWERAISPNKVPYYINHETQTTCWDHPKMQGPWERAISPNKVPYYINHETQT TCWDHPKMTELYQSLADLNNVRFSAYRTAMKLRRLQKALCLDLLSLSAACDALDQ HNLKQNDQPMDILQIINCLTTIYDRLEQEHNNLVNVPLCVDMCLNWLLNVYDTGRT GRIRVLSFKTGIISLCKAHLEDKYRYLFKQVASSTGFCDQRRLGLLLHDSIQIPRQLGE VASFGGSNIEPSVRSCFQFANNKPEIEAALFLDWMRLEPQSMVWLPVLHRVAAAETA KHQAKCNICKECPIIGFRYRSLKHFNYDICQSCFFSGRVAKGHKMHYPMVEYCTPTT SGEDVRDFAKVLKNKFRTKRYFAKHPRMGYLPVQTVLEGDNMETKHQAKCNICKE CPIIGFRYRSLKHFNYDICQSCFFSGRVAKGHKMHYPMVEYCTPTT

[0104] In some embodiments of any of the aspects, a dystrophin CR domain comprises asequence which has at least 80% sequence identity to the sequence of SEQ ID NO: 15. In some 31Attorney Docket No: 046192-000119WOPT 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: 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 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 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 lqkalcldll slsaacdald qhnlkqndqp mdilqiincl ttiydrleqe hnnlvnvplc vdmclnwlln vydtgrtgri rvlsfktgii slckahledk yrylfkqvas stgfcdqrrl glllhdsiqi prqlgevasf ggsniepsvr scfqfannkp eieaalfldw mrlepqsmvw lpvlhr

[0106] In some embodiments of any of the aspects, a utrophin SLR 3 domain comprises asequence 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 embodiments 32Attorney Docket No: 046192-000119WOPT of 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 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 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 asequence 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 dystroglycan 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 dystroglycan 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 ID 33Attorney Docket No: 046192-000119WOPT NO: 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 ryrslkhfny dicqscffsg rvakghkmhy pmveyctptt sgedvrdfak vlknkfrtkr yfakhprmgy lpvqtvlegd nmet

[0110] In some embodiments of any of the aspects, a dystroglycan binding domain comprises asequence 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. 34Attorney Docket No: 046192-000119WOPT

[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 ofSEQ 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 whichhas 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 polypeptide 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. 35Attorney Docket No: 046192-000119WOPT

[0114] In some embodiments of any of the aspects, the polypeptide comprises a sequence whichhas 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 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 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 polypeptide comprises a sequence whichhas 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 a 36Attorney Docket No: 046192-000119WOPT 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 comprises 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 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 rqttrpysqv nvlnfttswt 181 dglafnavlh rhkpdlfswd kvvkmspier lehafskaqt ylgieklldp edvavqlpdk 241 ksiimyltsl fevlpqqvti dairevetlp rkykkeceee ainiqstape eehespraet 301 pstvtevdmd ldsyqialee 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 fnrawteltd wlslldqvik 601 sqrvmvgdle dinemiikqk atmqdleqrr pqleelitaa qnlknktsnq eartiitdri 661 eriqnqwdev qehlqnrrqq lnemlkdstq wleakeeaeq vlgqarakle swkegpytvd 721 aiqkkitetk qlakdlrqwq tnvdvandla lkllrdysad dtrkvhmite ninaswrsih 781 krvsereaal eethrllqqf pldlekflaw lteaettanv lqdatrkerl ledskgvkel 841 mkqwqdlqge ieahtdvyhn ldensqkilr slegsddavl lqrrldnmnf kwselrkksl 901 nirshleass dqwkrlhlsl qellvwlqlk ddelsrqapi ggdfpavqkq ndvhrafkre 961 lktkepvims tletvriflt eqpleglekl yqeprelppe eraqnvtrll rkqaeevnte 1021 weklnlhsad wqrkidetle rlqelqeatd eldlklrqae vikgswqpvg dllidslqdh 1081 lekvkalrge iaplkenvsh vndlarqltt lgiqlspynl stledlntrw kllqvavedr 1141 vrqlheahrd fgpasqhfls tsvqgpwera ispnkvpyyi nhetqttcwd hpkmtelyqs 1201 ladlnnvrfs ayrtamklrr lqkalcldll slsaacdald qhnlkqndqp mdilqiincl 1261 ttiydrleqe hnnlvnvplc vdmclnwlln vydtgrtgri rvlsfktgii slckahledk 1321 yrylfkqvas stgfcdqrrl glllhdsiqi prqlgevasf ggsniepsvr scfqfannkp 1381 eieaalfldw mrlepqsmvw lpvlhrvaaa etakhqakcn ickecpiigf ryrslkhfny 1441 dicqscffsg rvakghkmhy pmveyctptt sgedvrdfak vlknkfrtkr yfakhprmgy 1501 lpvqtvlegd nmet

[0117] SI-trophin_09 protein (SEQ ID NO: 2)37Attorney Docket No: 046192-000119WOPT 1 makygeheas pdngqnefsd iiksrsdehn dvqkktftkw inarfsksgk ppindmftdl 61 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 ldsyqialee 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 lkawltekee alnkvqtsnf kdqkelsvsv rrlailkedm emkrqtldql seigqdvgql 601 ldnskaskki nsdseeltqr wdslvqrled ssnqvtqava klgmsqipqk dlletvrvre 661 qaitkkskqe lppppppkkr qihvaladfn rawteltdwl slldqviksq rvmvgdledi 721 nemiikqkat mqdleqrrpq leelitaaqn lknktsnqea rtiitdrier iqnqwdevqe 781 hlqnrrqqln emlkdstqwl eakeeaeqvl gqaraklesw kegpytvdai qkkitetkql 841 akdlrqwqtn vdvandlalk llrdysaddt rkvhmiteni naswrsihkr vsereaalee 901 thrllqqfpl dlekflawlt eaettanvlq datrkerlle dskgvkelmk qwqdlqgeie 961 ahtdvyhnld ensqkilrsl egsddavllq rrldnmnfkw selrkkslni rshleatler 1021 lqelqeatde ldlklrqaev ikgswqpvgd llidslqdhl ekvkalrgei aplkenvshv 1081 ndlarqlttl giqlspynls tledlntrwk llqvavedrv rqlheahrdf gpasqhflst 1141 svqgpwerai spnkvpyyin hetqttcwdh pkmtelyqsl adlnnvrfsa yrtamklrrl 1201 qkalcldlls lsaacdaldq hnlkqndqpm dilqiinclt tiydrleqeh nnlvnvplcv 1261 dmclnwllnv ydtgrtgrir vlsfktgiis lckahledky rylfkqvass tgfcdqrrlg 1321 lllhdsiqip rqlgevasfg gsniepsvrs cfqfannkpe ieaalfldwm rlepqsmvwl 1381 pvlhrvaaae takhqakcni ckecpiigfr yrslkhfnyd icqscffsgr vakghkmhyp 1441 mveyctptts gedvrdfakv lknkfrtkry 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 dglafnavlh rhkpdlfswd kvvkmspier lehafskaqt ylgieklldp edvavqlpdk 241 ksiimyltsl fevlpqqvti dairevetlp rkykkeceee ainiqstape eehespraet 301 pstvtevdmd ldsyqialee 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 fnrawteltd wlslldqvik 601 sqrvmvgdle dinemiikqk atmqdleqrr pqleelitaa qnlknktsnq eartiitdri 661 eriqnqwdev qehlqnrrqq lnemlkdstq wleakeeaeq vlgqarakle swkegpytvd 721 aiqkkitetk qlakdlrqwq tnvdvandla lkllrdysad dtrkvhmite ninaswrsih 781 krvsereaal eethrllqqf pldlekflaw lteaettanv lqdatrkerl ledskgvkel 841 mkqwqdlqge ieahtdvyhn ldensqkilr slegsddavl lqrrldnmnf kwselrkksl 901 nirshleatl erlqelqeat deldlklrqa evikgswqpv gdllidslqd hlekvkalrg 961 eiaplkenvs hvndlarqlt tlgiqlspyn lstledlntr wkllqvaved rvrqlheahr 1021 dfgpasqhfl stsvqgpwer aispnkvpyy inhetqttcw dhpkmtelyq sladlnnvrf 1081 sayrtamklr rlqkalcldl lslsaacdal dqhnlkqndq pmdilqiinc lttiydrleq 1141 ehnnlvnvpl cvdmclnwll nvydtgrtgr irvlsfktgi islckahled kyrylfkqva 1201 sstgfcdqrr lglllhdsiq iprqlgevas fggsniepsv rscfqfannk peieaalfld 1261 wmrlepqsmv wlpvlhrvaa aetakhqakc nickecpiig fryrslkhfn ydicqscffs 38Attorney Docket No: 046192-000119WOPT 1321 grvakghkmh ypmveyctpt tsgedvrdfa kvlknkfrtk ryfakhprmg ylpvqtvleg 1381 dnmet

[0119] SI-trophin_07_AE_nucleic acid sequence (SEQ ID NO: 85)ATGGCCAAGTATGGAGAACATGAAGCCAGTCCTGACAATGGGCAGAACGAATTCAGTGATATCAT TAAGTCCAGATCTGATGAACACAATGACGTACAGAAGAAAACCTTTACCAAATGGATAAATGCTC GATTTTCAAAGAGTGGGAAACCACCCATCAATGATATGTTCACAGACCTCAAAGATGGAAGGAAG CTATTGGATCTTCTAGAAGGCCTCACAGGAACATCACTGCCAAAGGAACGTGGTTCCACAAGGGT ACATGCCTTAAATAACGTCAACAGAGTGCTGCAGGTTTTACATCAGAACAATGTGGAATTAGTGA ATATAGGGGGAACTGACATTGTGGATGGAAATCACAAACTGACTTTGGGGTTACTTTGGAGCATC ATTTTGCACTGGCAGGTGAAAGATGTCATGAAGGATGTCATGTCGGACCTGCAGCAGACGAACAG TGAGAAGATCCTGCTCAGCTGGGTGCGTCAGACCACCAGGCCCTACAGCCAAGTCAACGTCCTCA ACTTCACCACCAGCTGGACAGATGGACTCGCCTTTAATGCTGTCCTCCACCGACATAAACCTGATC TCTTCAGCTGGGATAAAGTTGTCAAAATGTCACCAATTGAGAGACTTGAACATGCCTTCAGCAAGG CTCAAACTTATTTGGGAATTGAAAAGCTGTTAGATCCTGAAGATGTTGCCGTTCAGCTTCCTGACA AGAAATCCATAATTATGTATTTAACATCTTTGTTTGAGGTGCTACCTCAGCAAGTCACCATAGACG CCATCCGTGAGGTAGAGACACTCCCAAGGAAATATAAAAAAGAATGTGAAGAAGAGGCAATTAA TATACAGAGTACAGCGCCTGAGGAGGAGCATGAGAGTCCCCGAGCTGAAACTCCCAGCACTGTCA CTGAGGTTGACATGGATCTGGACAGCTATCAGATTGCGTTGGAGGAAGTGCTGACCTGGTTGCTTT CTGCTGAGGACACTTTCCAGGAGCAGGATGATATTTCTGATGATGTTGAAGAAGTCAAAGACCAG TTTGCAACCCATGAAGCTTTTATGATGGAACTGACTGCACACCAGAGCAGTGTGGGCAGCGTCCTG CAGGCAGGCAACCAACTGATAACACAAGGAACTCTGTCAGACGAAGAAGAATTTGAGATTCAGGA ACAGATGACCCTGCTGAATGCTAGATGGGAGGCTCTTAGGGTGGAGAGTATGGACAGACAGTCCC GGCTGCACGATGTGCTGATGGAACTGCAGAAGAAGCAACTGCAGCAGCTCTCCGCCTGGTTAACA CTCACAGAGGAGCGCATTCAGAAGATGGAAACTTGCCCCCTGGATGATGATGTAAAATCTCTACA AAAGCTGCTAGAAGAACATAAAAGTTTGCAAAGTGATCTTGAGGCTGAACAGGTGAAAGTAAATT CACTAACTCACATGGTGGTCATTGTTGATGAAAACAGTGGTGAGAGTGCTACAGCTATCCTAGAAG ACCAGTTACAGAAACTTGGTGAGCGCTGGACAGCAGTATGCCGTTGGACTGAAGAACGCTGGAAT AGGTTACAAGAAATCAATATAGCTGTAGCAAAGCTGGGGATGTCTCAGATTCCTCAGAAGGACCT TTTGGAGACTGTTCGTGTAAGAGAACAAGCAATTACAAAAAAATCTAAGCAGGAACTGCCTCCTC CTCCTCCCCCAAAGAAGAGACAGATCCATGTGGCTCTGGCAGATTTCAACCGGGCTTGGACAGAA CTTACCGACTGGCTTTCTCTGCTTGATCAAGTTATAAAATCACAGAGGGTGATGGTGGGTGACCTT GAGGATATCAACGAGATGATCATCAAGCAGAAGGCAACAATGCAGGATTTGGAACAGAGGCGTC CCCAGTTGGAAGAACTCATTACCGCTGCCCAAAATTTGAAAAACAAGACCAGCAATCAAGAGGCT AGAACAATCATTACGGATCGAATTGAAAGAATTCAGAATCAGTGGGATGAAGTACAAGAACACCT TCAGAACCGGAGGCAACAGTTGAATGAAATGTTAAAGGATTCAACACAATGGCTGGAAGCTAAGG AAGAAGCTGAGCAGGTCTTAGGACAGGCCAGAGCCAAGCTTGAGTCATGGAAGGAGGGTCCCTAT ACAGTAGATGCAATCCAAAAGAAAATCACAGAAACCAAGCAGTTGGCCAAAGACCTCCGCCAGTG GCAGACAAATGTAGATGTGGCAAATGACTTGGCCCTGAAACTTCTCCGGGATTATTCTGCAGATGA TACCAGAAAAGTCCACATGATAACAGAGAATATCAATGCCTCTTGGAGAAGCATTCATAAAAGGG TGAGTGAGCGAGAGGCTGCTTTGGAAGAAACTCATAGATTACTGCAACAGTTCCCCCTGGACCTG GAAAAGTTTCTTGCCTGGCTTACAGAAGCTGAAACAACTGCCAATGTCCTACAGGATGCTACCCGT AAGGAAAGGCTCCTAGAAGACTCCAAGGGAGTAAAAGAGCTGATGAAACAATGGCAAGACCTCC AAGGTGAAATTGAAGCTCACACAGATGTTTATCACAACCTGGATGAAAACAGCCAAAAAATCCTG AGATCCCTGGAAGGTTCCGATGATGCAGTCCTGTTACAAAGACGTTTGGATAACATGAACTTCAAG TGGAGTGAACTTCGGAAAAAGTCTCTCAACATTAGGTCCCATTTGGAAGCCAGTTCTGACCAGTGG AAGCGTCTGCACCTTTCTCTGCAGGAACTTCTGGTGTGGCTACAGCTGAAAGATGATGAATTAAGC CGGCAGGCACCTATTGGAGGCGACTTTCCAGCAGTTCAGAAGCAGAACGATGTACATAGGGCCTT CAAGAGGGAATTGAAAACTAAAGAACCTGTAATCATGAGTACTCTTGAGACTGTACGAATATTTCT GACAGAGCAGCCTTTGGAAGGACTAGAGAAACTCTACCAGGAGCCCAGAGAGCTGCCTCCTGAGG AGAGAGCCCAGAATGTCACTCGGCTTCTACGAAAGCAGGCTGAGGAGGTCAATACTGAGTGGGAA AAATTGAACCTGCACTCCGCTGACTGGCAGAGAAAAATAGATGAGACCCTTGAAAGACTCCGGGA ACTTCAAGAGGCCACGGATGAGCTGGACCTCAAGCTGCGCCAAGCTGAGGTGATCAAGGGATCCT GGCAGCCCGTGGGCGATCTCCTCATTGACTCTCTCCAAGATCACCTCGAGAAAGTCAAGGCACTTC GAGGAGAAATTGCGCCTCTGAAAGAGAACGTGAGCCACGTCAATGACCTTGCTCGCCAGCTTACC ACTTTGGGCATTCAGCTCTCACCGTATAACCTCAGCACTCTGGAAGACCTGAACACCAGATGGAAG CTTCTGCAGGTGGCCGTCGAGGACCGAGTCAGGCAGCTGCATGAAGCCCACAGGGACTTTGGTCC AGCATCTCAGCACTTTCTTTCCACGTCTGTCCAGGGTCCCTGGGAGAGAGCCATCTCGCCAAACAA 39Attorney Docket No: 046192-000119WOPT AGTGCCCTACTATATCAACCACGAGACTCAAACAACTTGCTGGGACCATCCCAAAATGACAGAGC TCTACCAGTCTTTAGCTGACCTGAATAATGTCAGATTCTCAGCTTATAGGACTGCCATGAAACTCC GAAGACTGCAGAAGGCCCTTTGCTTGGATCTCTTGAGCCTGTCAGCTGCATGTGATGCCTTGGACC AGCACAACCTCAAGCAAAATGACCAGCCCATGGATATCCTGCAGATTATTAATTGTTTGACCACTA TTTATGACCGCCTGGAGCAAGAGCACAACAATTTGGTCAACGTCCCTCTCTGCGTGGATATGTGTC TGAACTGGCTGCTGAATGTTTATGATACGGGACGAACAGGGAGGATCCGTGTCCTGTCTTTTAAAA CTGGCATCATTTCCCTGTGTAAAGCACATTTGGAAGACAAGTACAGATACCTTTTCAAGCAAGTGG CAAGTTCAACAGGATTTTGTGACCAGCGCAGGCTGGGCCTCCTTCTGCATGATTCTATCCAAATTC CAAGACAGTTGGGTGAAGTTGCATCCTTTGGGGGCAGTAACATTGAGCCAAGTGTCCGGAGCTGC TTCCAATTTGCTAATAATAAGCCAGAGATCGAAGCGGCCCTCTTCCTAGACTGGATGAGACTGGAA CCCCAGTCCATGGTGTGGCTGCCCGTCCTGCACAGAGTGGCTGCTGCAGAAACTGCCAAGCATCAG GCCAAATGTAACATCTGCAAAGAGTGTCCAATCATTGGATTCAGGTACAGGAGTCTAAAGCACTTT AATTATGACATCTGCCAAAGCTGCTTTTTTTCTGGTCGAGTTGCAAAAGGCCATAAAATGCACTAT CCCATGGTGGAATATTGCACTCCGACTACATCAGGAGAAGATGTTCGAGACTTTGCCAAGGTACTA AAAAACAAATTTCGAACCAAAAGGTATTTTGCGAAGCATCCCCGAATGGGCTACCTGCCAGTGCA GACTGTCTTAGAGGGGGACAACATGGAAACT

[0120] SI-trophin_09 nucleic acid sequence (SEQ ID NO: 86)ATGGCCAAGTATGGAGAACATGAAGCCAGTCCTGACAATGGGCAGAACGAATTCAGTGATATCAT TAAGTCCAGATCTGATGAACACAATGACGTACAGAAGAAAACCTTTACCAAATGGATAAATGCTC GATTTTCAAAGAGTGGGAAACCACCCATCAATGATATGTTCACAGACCTCAAAGATGGAAGGAAG CTATTGGATCTTCTAGAAGGCCTCACAGGAACATCACTGCCAAAGGAACGTGGTTCCACAAGGGT ACATGCCTTAAATAACGTCAACAGAGTGCTGCAGGTTTTACATCAGAACAATGTGGAATTAGTGA ATATAGGGGGAACTGACATTGTGGATGGAAATCACAAACTGACTTTGGGGTTACTTTGGAGCATC ATTTTGCACTGGCAGGTGAAAGATGTCATGAAGGATGTCATGTCGGACCTGCAGCAGACGAACAG TGAGAAGATCCTGCTCAGCTGGGTGCGTCAGACCACCAGGCCCTACAGCCAAGTCAACGTCCTCA ACTTCACCACCAGCTGGACAGATGGACTCGCCTTTAATGCTGTCCTCCACCGACATAAACCTGATC TCTTCAGCTGGGATAAAGTTGTCAAAATGTCACCAATTGAGAGACTTGAACATGCCTTCAGCAAGG CTCAAACTTATTTGGGAATTGAAAAGCTGTTAGATCCTGAAGATGTTGCCGTTCAGCTTCCTGACA AGAAATCCATAATTATGTATTTAACATCTTTGTTTGAGGTGCTACCTCAGCAAGTCACCATAGACG CCATCCGTGAGGTAGAGACACTCCCAAGGAAATATAAAAAAGAATGTGAAGAAGAGGCAATTAA TATACAGAGTACAGCGCCTGAGGAGGAGCATGAGAGTCCCCGAGCTGAAACTCCCAGCACTGTCA CTGAGGTTGACATGGATCTGGACAGCTATCAGATTGCGTTGGAGGAAGTGCTGACCTGGTTGCTTT CTGCTGAGGACACTTTCCAGGAGCAGGATGATATTTCTGATGATGTTGAAGAAGTCAAAGACCAG TTTGCAACCCATGAAGCTTTTATGATGGAACTGACTGCACACCAGAGCAGTGTGGGCAGCGTCCTG CAGGCAGGCAACCAACTGATAACACAAGGAACTCTGTCAGACGAAGAAGAATTTGAGATTCAGGA ACAGATGACCCTGCTGAATGCTAGATGGGAGGCTCTTAGGGTGGAGAGTATGGACAGACAGTCCC GGCTGCACGATGTGCTGATGGAACTGCAGAAGAAGCAACTGCAGCAGCTCTCCGCCTGGTTAACA CTCACAGAGGAGCGCATTCAGAAGATGGAAACTTGCCCCCTGGATGATGATGTAAAATCTCTACA AAAGCTGCTAGAAGAACATAAAAGTTTGCAAAGTGATCTTGAGGCTGAACAGGTGAAAGTAAATT CACTAACTCACATGGTGGTCATTGTTGATGAAAACAGTGGTGAGAGTGCTACAGCTATCCTAGAAG ACCAGTTACAGAAACTTGGTGAGCGCTGGACAGCAGTATGCCGTTGGACTGAAGAACGCTGGAAT AGGTTACAAGAAATCAATATATTGTGGCAGGAATTATTGGAAGAACAGTGCTTGTTGAAAGCTTG GTTAACCGAAAAAGAAGAGGCTTTAAATAAAGTCCAGACAAGCAACTTCAAAGACCAAAAGGAA CTAAGTGTCAGTGTTCGACGTCTGGCTATTTTGAAGGAAGACATGGAAATGAAGCGTCAAACATTG GATCAGCTGAGTGAGATTGGCCAGGATGTGGGACAATTACTTGATAATTCCAAGGCATCTAAGAA GATCAACAGTGACTCAGAGGAACTGACTCAAAGATGGGATTCTTTGGTTCAGAGACTAGAAGATT CCTCCAACCAGGTGACTCAGGCTGTAGCAAAGCTGGGGATGTCTCAGATTCCTCAGAAGGACCTTT TGGAGACTGTTCGTGTAAGAGAACAAGCAATTACAAAAAAATCTAAGCAGGAACTGCCTCCTCCT CCTCCCCCAAAGAAGAGACAGATCCATGTGGCTCTGGCAGATTTCAACCGGGCTTGGACAGAACT TACCGACTGGCTTTCTCTGCTTGATCAAGTTATAAAATCACAGAGGGTGATGGTGGGTGACCTTGA GGATATCAACGAGATGATCATCAAGCAGAAGGCAACAATGCAGGATTTGGAACAGAGGCGTCCCC AGTTGGAAGAACTCATTACCGCTGCCCAAAATTTGAAAAACAAGACCAGCAATCAAGAGGCTAGA ACAATCATTACGGATCGAATTGAAAGAATTCAGAATCAGTGGGATGAAGTACAAGAACACCTTCA GAACCGGAGGCAACAGTTGAATGAAATGTTAAAGGATTCAACACAATGGCTGGAAGCTAAGGAA GAAGCTGAGCAGGTCTTAGGACAGGCCAGAGCCAAGCTTGAGTCATGGAAGGAGGGTCCCTATAC 40Attorney Docket No: 046192-000119WOPT AGTAGATGCAATCCAAAAGAAAATCACAGAAACCAAGCAGTTGGCCAAAGACCTCCGCCAGTGGC AGACAAATGTAGATGTGGCAAATGACTTGGCCCTGAAACTTCTCCGGGATTATTCTGCAGATGATA CCAGAAAAGTCCACATGATAACAGAGAATATCAATGCCTCTTGGAGAAGCATTCATAAAAGGGTG AGTGAGCGAGAGGCTGCTTTGGAAGAAACTCATAGATTACTGCAACAGTTCCCCCTGGACCTGGA AAAGTTTCTTGCCTGGCTTACAGAAGCTGAAACAACTGCCAATGTCCTACAGGATGCTACCCGTAA GGAAAGGCTCCTAGAAGACTCCAAGGGAGTAAAAGAGCTGATGAAACAATGGCAAGACCTCCAA GGTGAAATTGAAGCTCACACAGATGTTTATCACAACCTGGATGAAAACAGCCAAAAAATCCTGAG ATCCCTGGAAGGTTCCGATGATGCAGTCCTGTTACAAAGACGTTTGGATAACATGAACTTCAAGTG GAGTGAACTTCGGAAAAAGTCTCTCAACATTAGGTCCCATTTGGAAGCCACCCTTGAAAGACTCCG GGAACTTCAAGAGGCCACGGATGAGCTGGACCTCAAGCTGCGCCAAGCTGAGGTGATCAAGGGAT CCTGGCAGCCCGTGGGCGATCTCCTCATTGACTCTCTCCAAGATCACCTCGAGAAAGTCAAGGCAC TTCGAGGAGAAATTGCGCCTCTGAAAGAGAACGTGAGCCACGTCAATGACCTTGCTCGCCAGCTT ACCACTTTGGGCATTCAGCTCTCACCGTATAACCTCAGCACTCTGGAAGACCTGAACACCAGATGG AAGCTTCTGCAGGTGGCCGTCGAGGACCGAGTCAGGCAGCTGCATGAAGCCCACAGGGACTTTGG TCCAGCATCTCAGCACTTTCTTTCCACGTCTGTCCAGGGTCCCTGGGAGAGAGCCATCTCGCCAAA CAAAGTGCCCTACTATATCAACCACGAGACTCAAACAACTTGCTGGGACCATCCCAAAATGACAG AGCTCTACCAGTCTTTAGCTGACCTGAATAATGTCAGATTCTCAGCTTATAGGACTGCCATGAAAC TCCGAAGACTGCAGAAGGCCCTTTGCTTGGATCTCTTGAGCCTGTCAGCTGCATGTGATGCCTTGG ACCAGCACAACCTCAAGCAAAATGACCAGCCCATGGATATCCTGCAGATTATTAATTGTTTGACCA CTATTTATGACCGCCTGGAGCAAGAGCACAACAATTTGGTCAACGTCCCTCTCTGCGTGGATATGT GTCTGAACTGGCTGCTGAATGTTTATGATACGGGACGAACAGGGAGGATCCGTGTCCTGTCTTTTA AAACTGGCATCATTTCCCTGTGTAAAGCACATTTGGAAGACAAGTACAGATACCTTTTCAAGCAAG TGGCAAGTTCAACAGGATTTTGTGACCAGCGCAGGCTGGGCCTCCTTCTGCATGATTCTATCCAAA TTCCAAGACAGTTGGGTGAAGTTGCATCCTTTGGGGGCAGTAACATTGAGCCAAGTGTCCGGAGCT GCTTCCAATTTGCTAATAATAAGCCAGAGATCGAAGCGGCCCTCTTCCTAGACTGGATGAGACTGG AACCCCAGTCCATGGTGTGGCTGCCCGTCCTGCACAGAGTGGCTGCTGCAGAAACTGCCAAGCATC AGGCCAAATGTAACATCTGCAAAGAGTGTCCAATCATTGGATTCAGGTACAGGAGTCTAAAGCAC TTTAATTATGACATCTGCCAAAGCTGCTTTTTTTCTGGTCGAGTTGCAAAAGGCCATAAAATGCACT ATCCCATGGTGGAATATTGCACTCCGACTACATCAGGAGAAGATGTTCGAGACTTTGCCAAGGTAC TAAAAAACAAATTTCGAACCAAAAGGTATTTTGCGAAGCATCCCCGAATGGGCTACCTGCCAGTG CAGACTGTCTTAGAGGGGGACAACATGGAAACT

[0121] SI-trophin_09_AE nucleic acid sequence (SEQ ID NO: 87)ATGGCCAAGTATGGAGAACATGAAGCCAGTCCTGACAATGGGCAGAACGAATTCAGTGATATCAT TAAGTCCAGATCTGATGAACACAATGACGTACAGAAGAAAACCTTTACCAAATGGATAAATGCTC GATTTTCAAAGAGTGGGAAACCACCCATCAATGATATGTTCACAGACCTCAAAGATGGAAGGAAG CTATTGGATCTTCTAGAAGGCCTCACAGGAACATCACTGCCAAAGGAACGTGGTTCCACAAGGGT ACATGCCTTAAATAACGTCAACAGAGTGCTGCAGGTTTTACATCAGAACAATGTGGAATTAGTGA ATATAGGGGGAACTGACATTGTGGATGGAAATCACAAACTGACTTTGGGGTTACTTTGGAGCATC ATTTTGCACTGGCAGGTGAAAGATGTCATGAAGGATGTCATGTCGGACCTGCAGCAGACGAACAG TGAGAAGATCCTGCTCAGCTGGGTGCGTCAGACCACCAGGCCCTACAGCCAAGTCAACGTCCTCA ACTTCACCACCAGCTGGACAGATGGACTCGCCTTTAATGCTGTCCTCCACCGACATAAACCTGATC TCTTCAGCTGGGATAAAGTTGTCAAAATGTCACCAATTGAGAGACTTGAACATGCCTTCAGCAAGG CTCAAACTTATTTGGGAATTGAAAAGCTGTTAGATCCTGAAGATGTTGCCGTTCAGCTTCCTGACA AGAAATCCATAATTATGTATTTAACATCTTTGTTTGAGGTGCTACCTCAGCAAGTCACCATAGACG CCATCCGTGAGGTAGAGACACTCCCAAGGAAATATAAAAAAGAATGTGAAGAAGAGGCAATTAA TATACAGAGTACAGCGCCTGAGGAGGAGCATGAGAGTCCCCGAGCTGAAACTCCCAGCACTGTCA CTGAGGTTGACATGGATCTGGACAGCTATCAGATTGCGTTGGAGGAAGTGCTGACCTGGTTGCTTT CTGCTGAGGACACTTTCCAGGAGCAGGATGATATTTCTGATGATGTTGAAGAAGTCAAAGACCAG TTTGCAACCCATGAAGCTTTTATGATGGAACTGACTGCACACCAGAGCAGTGTGGGCAGCGTCCTG CAGGCAGGCAACCAACTGATAACACAAGGAACTCTGTCAGACGAAGAAGAATTTGAGATTCAGGA ACAGATGACCCTGCTGAATGCTAGATGGGAGGCTCTTAGGGTGGAGAGTATGGACAGACAGTCCC GGCTGCACGATGTGCTGATGGAACTGCAGAAGAAGCAACTGCAGCAGCTCTCCGCCTGGTTAACA CTCACAGAGGAGCGCATTCAGAAGATGGAAACTTGCCCCCTGGATGATGATGTAAAATCTCTACA AAAGCTGCTAGAAGAACATAAAAGTTTGCAAAGTGATCTTGAGGCTGAACAGGTGAAAGTAAATT CACTAACTCACATGGTGGTCATTGTTGATGAAAACAGTGGTGAGAGTGCTACAGCTATCCTAGAAG 41Attorney Docket No: 046192-000119WOPT ACCAGTTACAGAAACTTGGTGAGCGCTGGACAGCAGTATGCCGTTGGACTGAAGAACGCTGGAAT AGGTTACAAGAAATCAATATAGCTGTAGCAAAGCTGGGGATGTCTCAGATTCCTCAGAAGGACCT TTTGGAGACTGTTCGTGTAAGAGAACAAGCAATTACAAAAAAATCTAAGCAGGAACTGCCTCCTC CTCCTCCCCCAAAGAAGAGACAGATCCATGTGGCTCTGGCAGATTTCAACCGGGCTTGGACAGAA CTTACCGACTGGCTTTCTCTGCTTGATCAAGTTATAAAATCACAGAGGGTGATGGTGGGTGACCTT GAGGATATCAACGAGATGATCATCAAGCAGAAGGCAACAATGCAGGATTTGGAACAGAGGCGTC CCCAGTTGGAAGAACTCATTACCGCTGCCCAAAATTTGAAAAACAAGACCAGCAATCAAGAGGCT AGAACAATCATTACGGATCGAATTGAAAGAATTCAGAATCAGTGGGATGAAGTACAAGAACACCT TCAGAACCGGAGGCAACAGTTGAATGAAATGTTAAAGGATTCAACACAATGGCTGGAAGCTAAGG AAGAAGCTGAGCAGGTCTTAGGACAGGCCAGAGCCAAGCTTGAGTCATGGAAGGAGGGTCCCTAT ACAGTAGATGCAATCCAAAAGAAAATCACAGAAACCAAGCAGTTGGCCAAAGACCTCCGCCAGTG GCAGACAAATGTAGATGTGGCAAATGACTTGGCCCTGAAACTTCTCCGGGATTATTCTGCAGATGA TACCAGAAAAGTCCACATGATAACAGAGAATATCAATGCCTCTTGGAGAAGCATTCATAAAAGGG TGAGTGAGCGAGAGGCTGCTTTGGAAGAAACTCATAGATTACTGCAACAGTTCCCCCTGGACCTG GAAAAGTTTCTTGCCTGGCTTACAGAAGCTGAAACAACTGCCAATGTCCTACAGGATGCTACCCGT AAGGAAAGGCTCCTAGAAGACTCCAAGGGAGTAAAAGAGCTGATGAAACAATGGCAAGACCTCC AAGGTGAAATTGAAGCTCACACAGATGTTTATCACAACCTGGATGAAAACAGCCAAAAAATCCTG AGATCCCTGGAAGGTTCCGATGATGCAGTCCTGTTACAAAGACGTTTGGATAACATGAACTTCAAG TGGAGTGAACTTCGGAAAAAGTCTCTCAACATTAGGTCCCATTTGGAAGCCACCCTTGAAAGACTC CGGGAACTTCAAGAGGCCACGGATGAGCTGGACCTCAAGCTGCGCCAAGCTGAGGTGATCAAGGG ATCCTGGCAGCCCGTGGGCGATCTCCTCATTGACTCTCTCCAAGATCACCTCGAGAAAGTCAAGGC ACTTCGAGGAGAAATTGCGCCTCTGAAAGAGAACGTGAGCCACGTCAATGACCTTGCTCGCCAGC TTACCACTTTGGGCATTCAGCTCTCACCGTATAACCTCAGCACTCTGGAAGACCTGAACACCAGAT GGAAGCTTCTGCAGGTGGCCGTCGAGGACCGAGTCAGGCAGCTGCATGAAGCCCACAGGGACTTT GGTCCAGCATCTCAGCACTTTCTTTCCACGTCTGTCCAGGGTCCCTGGGAGAGAGCCATCTCGCCA AACAAAGTGCCCTACTATATCAACCACGAGACTCAAACAACTTGCTGGGACCATCCCAAAATGAC AGAGCTCTACCAGTCTTTAGCTGACCTGAATAATGTCAGATTCTCAGCTTATAGGACTGCCATGAA ACTCCGAAGACTGCAGAAGGCCCTTTGCTTGGATCTCTTGAGCCTGTCAGCTGCATGTGATGCCTT GGACCAGCACAACCTCAAGCAAAATGACCAGCCCATGGATATCCTGCAGATTATTAATTGTTTGAC CACTATTTATGACCGCCTGGAGCAAGAGCACAACAATTTGGTCAACGTCCCTCTCTGCGTGGATAT GTGTCTGAACTGGCTGCTGAATGTTTATGATACGGGACGAACAGGGAGGATCCGTGTCCTGTCTTT TAAAACTGGCATCATTTCCCTGTGTAAAGCACATTTGGAAGACAAGTACAGATACCTTTTCAAGCA AGTGGCAAGTTCAACAGGATTTTGTGACCAGCGCAGGCTGGGCCTCCTTCTGCATGATTCTATCCA AATTCCAAGACAGTTGGGTGAAGTTGCATCCTTTGGGGGCAGTAACATTGAGCCAAGTGTCCGGA GCTGCTTCCAATTTGCTAATAATAAGCCAGAGATCGAAGCGGCCCTCTTCCTAGACTGGATGAGAC TGGAACCCCAGTCCATGGTGTGGCTGCCCGTCCTGCACAGAGTGGCTGCTGCAGAAACTGCCAAG CATCAGGCCAAATGTAACATCTGCAAAGAGTGTCCAATCATTGGATTCAGGTACAGGAGTCTAAA GCACTTTAATTATGACATCTGCCAAAGCTGCTTTTTTTCTGGTCGAGTTGCAAAAGGCCATAAAAT GCACTATCCCATGGTGGAATATTGCACTCCGACTACATCAGGAGAAGATGTTCGAGACTTTGCCAA GGTACTAAAAAACAAATTTCGAACCAAAAGGTATTTTGCGAAGCATCCCCGAATGGGCTACCTGC CAGTGCAGACTGTCTTAGAGGGGGACAACATGGAAACTAGGCCTAATAAAGAGCTCAGATGCATC GATCAGAGTGTGTTGGTTTTTTGTGTG

[0122] In some embodiments of any of the aspects, the polypeptide is engineered. In someembodiments of any of the aspects, the polypeptide 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% sequenceidentity 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). In 42Attorney Docket No: 046192-000119WOPT some embodiments of any of the aspects, the polypeptide has less than 60% sequence identity to wild- type dystrophin (e.g., SEQ ID NO: 30).

[0124] In some embodiments of any of the aspects, the polypeptide has less than 95% sequenceidentity 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 isoform Dp427m (e.g., SEQ ID NO: 668).

[0125] SEQ ID NO: 668. Dystrophin isoform Dp427m [Homo sapiens]; NCBI ref seq:NP_003997 1 mlwweevedc yeredvqkkt ftkwvnaqfs kfgkqhienl fsdlqdgrrl ldllegltgq 61 klpkekgstr vhalnnvnka lrvlqnnnvd lvnigstdiv dgnhkltlgl iwniilhwqv 121 knvmknimag lqqtnsekil lswvrqstrn ypqvnvinft tswsdglaln alihshrpdl 181 fdwnsvvcqq satqrlehaf niaryqlgie klldpedvdt typdkksilm yitslfqvlp 241 qqvsieaiqe vemlprppkv tkeehfqlhh qmhysqqitv slaqgyerts spkprfksya 301 ytqaayvtts dptrspfpsq hleapedksf gsslmesevn ldryqtalee vlswllsaed 361 tlqaqgeisn dvevvkdqfh thegymmdlt ahqgrvgnil qlgskligtg klsedeetev 421 qeqmnllnsr weclrvasme kqsnlhrvlm dlqnqklkel ndwltkteer trkmeeeplg 481 pdledlkrqv qqhkvlqedl eqeqvrvnsl thmvvvvdes sgdhataale eqlkvlgdrw 541 anicrwtedr wvllqdillk wqrlteeqcl fsawlseked avnkihttgf kdqnemlssl 601 qklavlkadl ekkkqsmgkl yslkqdllst lknksvtqkt eawldnfarc wdnlvqklek 661 staqisqavt ttqpsltqtt vmetvttvtt reqilvkhaq eelpppppqk krqitvdsei 721 rkrldvdite lhswitrsea 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 pseisrkyqs 1021 efeeiegrwk klssqlvehc qkleeqmnkl rkiqnhiqtl kkwmaevdvf lkeewpalgd 1081 seilkkqlkq crllvsdiqt iqpslnsvne ggqkikneae pefasrlete lkelntqwdh 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 nqgkeaaqrv 43Attorney Docket No: 046192-000119WOPT 1441 lsqidvaqkk lqdvsmkfrl fqkpanfeqr lqeskmilde vkmhlpalet ksveqevvqs 1501 qlnhcvnlyk slsevkseve mviktgrqiv qkkqtenpke ldervtalkl hynelgakvt 1561 erkqqlekcl klsrkmrkem nvltewlaat dmeltkrsav egmpsnldse vawgkatqke 1621 iekqkvhlks itevgealkt vlgkketlve dklsllnsnw iavtsraeew lnllleyqkh 1681 metfdqnvdh itkwiiqadt lldesekkkp qqkedvlkrl kaelndirpk vdstrdqaan 1741 lmanrgdhcr klvepqisel nhrfaaishr iktgkasipl keleqfnsdi qkllepleae 1801 iqqgvnlkee dfnkdmnedn egtvkellqr gdnlqqritd erkreeikik qqllqtkhna 1861 lkdlrsqrrk kaleishqwy qykrqaddll kclddiekkl aslpeprder kikeidrelq 1921 kkkeelnavr rqaeglsedg aamaveptqi qlskrwreie skfaqfrrln faqihtvree 1981 tmmvmtedmp leisyvpsty lteithvsqa lleveqllna pdlcakdfed lfkqeeslkn 2041 ikdslqqssg ridiihskkt aalqsatpve rvklqealsq ldfqwekvnk mykdrqgrfd 2101 rsvekwrrfh ydikifnqwl teaeqflrkt qipenwehak ykwylkelqd gigqrqtvvr 2161 tlnatgeeii qqssktdasi lqeklgslnl rwqevckqls drkkrleeqk nilsefqrdl 2221 nefvlwleea dniasiplep gkeqqlkekl eqvkllveel plrqgilkql netggpvlvs 2281 apispeeqdk lenklkqtnl qwikvsralp ekqgeieaqi kdlgqlekkl edleeqlnhl 2341 llwlspirnq leiynqpnqe gpfdvketei avqakqpdve eilskgqhly kekpatqpvk 2401 rkledlssew kavnrllqel rakqpdlapg lttigasptq tvtlvtqpvv 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 lqqfpldlek 2701 flawlteaet tanvlqdatr kerlledskg vkelmkqwqd lqgeieahtd vyhnldensq 2761 kilrslegsd davllqrrld nmnfkwselr kkslnirshl eassdqwkrl hlslqellvw 2821 lqlkddelsr qapiggdfpa vqkqndvhra fkrelktkep vimstletvr iflteqpleg 2881 leklyqepre lppeeraqnv trllrkqaee vnteweklnl hsadwqrkid etlerlrelq 2941 eatdeldlkl rqaevikgsw qpvgdllids lqdhlekvka lrgeiaplke nvshvndlar 3001 qlttlgiqls pynlstledl ntrwkllqva vedrvrqlhe ahrdfgpasq hflstsvqgp 3061 weraispnkv pyyinhetqt tcwdhpkmte lyqsladlnn vrfsayrtam klrrlqkalc 3121 ldllslsaac daldqhnlkq ndqpmdilqi inclttiydr leqehnnlvn vplcvdmcln 3181 wllnvydtgr tgrirvlsfk tgiislckah ledkyrylfk qvasstgfcd qrrlglllhd 3241 siqiprqlge vasfggsnie psvrscfqfa nnkpeieaal fldwmrlepq smvwlpvlhr 3301 vaaaetakhq akcnickecp iigfryrslk hfnydicqsc ffsgrvakgh kmhypmveyc 3361 tpttsgedvr dfakvlknkf rtkryfakhp rmgylpvqtv legdnmetpv tlinfwpvds 3421 apasspqlsh ddthsriehy asrlaemens ngsylndsis pnesiddehl liqhycqsln 3481 qdsplsqprs paqilisles eergeleril adleeenrnl qaeydrlkqq hehkglsplp 3541 sppemmptsp qsprdaelia eakllrqhkg rlearmqile dhnkqlesql hrlrqlleqp 44Attorney Docket No: 046192-000119WOPT 3601 qaeakvngtt vsspstslqr sdssqpmllr vvgsqtsdsm geedllsppq dtstgleevm 3661 eqlnnsfpss rgrntpgkpm redtm

[0126] In some embodiments of any of the aspects, the polypeptide has less than 95% sequenceidentity 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 wild- type 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-type 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 ppindmftdl 61 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 ldsyqialee 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 lkawltekee alnkvqtsnf kdqkelsvsv rrlailkedm emkrqtldql seigqdvgql 601 ldnskaskki nsdseeltqr wdslvqrled ssnqvtqava klgmsqipqk dlletvrvre 661 qaitkkskqe lppppppkkr qihvdieakk kfdaisaell nwilkwktai qtteikeymk 721 mqdtsemkkk lkalekeqre ripradelnq tgqilveqmg keglpteeik nvlekvssew 781 knvsqhledl erkiqlqedi nayfkqldel ekviktkeew vkhtsisess rqslpslkds 841 cqreltnllg lhpkiemara 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 qeltselnvv lenyqllcnr irgkchtlee vwscwiellh yldlettwln tleermkste 1261 vlpektdavn ealeslesvl rhpadnrtqi relgqtlidg gilddiisek leafnsryed 1321 lshlaeskqi slekqlqvlr etdqmlqvlq eslgeldkql ttyltdrida fqvpqeaqki 1381 qaeisahelt leelrrnmrs qpltspesrt arggsqmdvl qrklrevstk fqlfqkpanf 1441 eqrmldckrv ldgvkaelhv ldvkdvdpdv iqthldkcmk lyktlsevkl evetviktgr 1501 hivqkqqtdn pkgmdeqlts lkvlyndlga qvtegkqdle rasqlarkmk keaaslsewl 1561 satetelvqk stsegllgdl dteiswaknv lkdlekrkad lntitessaa lqnliegsep 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 lcmddvelsl nvpelntaiy edfsfqedsl knikdqldkl 1921 geqiavihek qpdvileasg peaiqirdtl tqlnakwdri nrmysdrkgc fdrameewrq 1981 fhcdlndltq witeaeellv dtcapggsld lekarihqqe levgisshqp sfaalnrtgd 2041 givqklsqad gsflkeklag lnqrwdaiva evkdrqprlk geskqvmkyr hqldeiicwl 2101 tkaehamqkr sttelgenlq elrdltqeme vhaeklkwln rtelemlsdk slslperdki 2161 seslrtvnmt wnkicrevpt tlkeciqeps svsqtriaah pnvqkvvlvs sasdipvqsh 2221 rtseisipad ldktitelad wlvlidqmlk snivtvgdve einktvsrmk itkadleqrh 2281 pqldyvftla qnlknkasss dmrtaitekl ervknqwdgt qhgvelrqqq ledmiidslq 2341 wddhreetee lmrkyearly ilqqarrdpl tkqisdnqil lqelgpgdgi vmafdnvlqk 2401 lleeygsddt rnvketteyl ktswinlkqs iadrqnalea ewrtvqasrr dlenflkwiq 2461 eaettvnvlv dashrenalq dsilarelkq qmqdiqaeid ahndifksid gnrqkmvkal 45Attorney Docket No: 046192-000119WOPT 2521 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 ltttydgleq mhkdlvnvpl cvdmclnwll 2941 nvydtgrtgk irvqslkigl mslskgllee kyrylfkeva gptemcdqrq lglllhdaiq 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 lrqhkgrlea 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 ofdystrophin 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: adystrophin 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 does not comprise any of: adystrophin 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: adystrophin 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: adystrophin NT domain and a dystrophin hinge 1 domain.

[0134] In some embodiments of any of the aspects, the polypeptide does not comprise any of: autrophin 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 apolypeptide 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. 46Attorney Docket No: 046192-000119WOPT

[0136] In some embodiments of any of the aspects, the polypeptide does not comprise apolypeptide 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 GCAGCACAAAGTGCTGCAGGAGGACCTGGAGCAGGAGCAGGTGCGCGTGAACAGCCTG 47Attorney Docket No: 046192-000119WOPT ACCCACATGGTGGTGGTCGTGGACGAGAGCAGCGGCGACCACGCCACAGCCGCCCTGGA AGAGCAGCTGAAAGTGCTGGGCGACAGATGGGCCAATATTTGTAGGTGGACCGAGGACA GATGGGTGCTGCTGCAGGACCAGCCCGACCTGGCCCCTGGCCTGACCACCATCGGCGCC AGCCCCACCCAGACCGTGACCCTGGTGACCCAGCCCGTGGTGACAAAGGAGACCGCCAT CAGCAAGCTGGAGATGCCCAGCTCCCTGATGCTGGAAGTGCCCACCCACCGCCTGCTCCA GCAGTTCCCCCTGGACCTGGAGAAGTTCCTGGCCTGGCTGACCGAGGCCGAAACCACCG CCAATGTGCTCCAGGACGCCACTAGAAAGGAGAGGCTGCTGGAGGACAGCAAGGGCGT GAAAGAGCTGATGAAGCAGTGGCAGGATCTGCAGGGCGAAATCGAGGCCCACACCGAC GTGTACCACAACCTGGACGAGAACAGCCAGAAGATTCTGAGGAGCCTGGAGGGCAGCG ACGACGCCGTCCTGCTCCAGAGGAGGCTGGACAACATGAACTTCAAGTGGAGCGAGCTG CGGAAGAAGAGCCTGAACATCCGGAGCCACCTGGAAGCCAGCAGCGACCAGTGGAAGA GACTGCACCTGAGCCTGCAGGAGCTGCTGGTGTGGCTGCAGCTGAAGGACGACGAGCTG AGCAGACAGGCCCCCATCGGCGGCGACTTCCCCGCCGTGCAGAAGCAGAACGACGTGCA CCGGGCCTTCAAGAGGGAGCTGAAAACCAAGGAACCCGTGATCATGAGCACCCTGGAGA CAGTGCGGATCTTCCTGACCGAGCAGCCCCTGGAGGGACTGGAGAAGCTGTACCAGGAG CCCAGAGAGCTGCCCCCCGAGGAGAGAGCCCAGAACGTGACCAGGCTGCTGAGAAAGC AGGCCGAGGAAGTGAATACCGAGTGGGAGAAGCTGAATCTGCACAGCGCCGACTGGCA GAGAAAGATCGACGAGACCCTGGAGAGACTCCAGGAACTGCAGGAAGCCACCGACGAG CTGGACCTGAAGCTGAGACAGGCCGAAGTGATCAAGGGCAGCTGGCAGCCTGTGGGCGA TCTGCTGATCGACTCCCTGCAGGATCACCTGGAGAAAGTGAAGGCCCTGCGGGGCGAGA TCGCCCCCCTGAAGGAGAATGTGAGCCACGTGAACGACCTGGCCAGACAGCTGACCACC CTGGGCATCCAGCTGAGCCCCTACAACCTGAGCACACTGGAGGATCTGAACACCCGGTG GAAACTGCTGCAGGTGGCCGTGGAGGATAGAGTGAGGCAGCTGCACGAAGCCCACAGA GACTTCGGCCCTGCCTCCCAGCACTTCCTGAGCACCAGCGTGCAGGGCCCCTGGGAGAG AGCCATCTCCCCCAACAAAGTGCCCTACTACATCAACCACGAGACCCAGACCACCTGCTG GGACCACCCTAAGATGACCGAGCTGTATCAGAGCCTGGCCGACCTGAACAATGTGCGGT TCAGCGCCTACAGAACCGCCATGAAGCTGCGGAGACTGCAGAAGGCCCTGTGCCTGGAT CTGCTGAGCCTGAGCGCCGCCTGCGACGCCCTGGACCAGCACAACCTGAAGCAGAATGA CCAGCCCATGGACATCCTGCAGATCATCAACTGCCTGACCACAATCTACGACCGGCTGGA ACAGGAGCACAACAACCTGGTGAATGTGCCCCTGTGCGTGGACATGTGCCTGAATTGGC TGCTGAACGTGTACGACACCGGCAGGACCGGCAGAATCCGCGTGCTGAGCTTCAAGACC GGCATCATCAGCCTGTGCAAGGCCCACCTGGAGGATAAGTACCGCTACCTGTTCAAGCA GGTGGCCAGCAGCACCGGCTTCTGCGATCAGAGGAGACTGGGCCTGCTGCTGCACGATA GCATCCAGATCCCTAGGCAGCTGGGCGAAGTGGCCAGCTTTGGCGGCAGCAACATCGAG CCCTCTGTGAGGAGCTGCTTCCAGTTCGCCAACAACAAGCCCGAGATCGAGGCCGCCCTG TTCCTGGACTGGATGAGGCTGGAGCCTCAGAGCATGGTGTGGCTGCCTGTGCTGCACAGA 48Attorney Docket No: 046192-000119WOPT GTGGCCGCCGCCGAGACCGCCAAGCACCAGGCCAAGTGCAATATCTGCAAGGAGTGCCC CATCATCGGCTTCCGGTACAGGAGCCTGAAGCACTTCAACTACGACATCTGCCAGAGCTG CTTTTTCAGCGGCAGAGTGGCCAAGGGCCACAAAATGCACTACCCCATGGTGGAGTACT GCACCCCCACCACCTCCGGCGAGGATGTGAGAGACTTCGCCAAAGTGCTGAAGAATAAG TTCCGGACCAAGCGGTACTTTGCCAAGCACCCCAGGATGGGCTACCTGCCCGTGCAGACC GTGCTGGAAGGCGACAACATGGAGACCTGA

[0138] SEQ ID NO: 601ATGGCCAAGTATGGGGACCTTGAAGCCAGGCCTGATGATGGGCAGAACGAATTCAGTGA CATCATTAAGTCCAGATCTGATGAACACAATGATGTACAGAAGAAAACCTTTACCAAAT GGATAAACGCTCGATTTTCCAAGAGTGGGAAACCACCCATCAGTGATATGTTCTCAGACC TCAAAGATGGGAGAAAGCTCTTGGATCTTCTCGAAGGCCTCACAGGAACATCATTGCCA AAGGAACGTGGTTCCACAAGGGTGCATGCCTTAAACAATGTCAACCGAGTGCTACAGGT TTTACATCAGAACAATGTGGACTTGGTGAATATTGGAGGCACGGACATTGTGGATGGAA ATCCCAAGCTGACTTTAGGGTTACTCTGGAGCATCATTCTGCACTGGCAGGTGAAGGATG TCATGAAAGATATCATGTCAGACCTGCAGCAGACAAACAGCGAGAAGATCCTGCTGAGC TGGGTGCGGCAGACCACCAGGCCCTACAGTCAAGTCAACGTCCTCAACTTCACCACCAG CTGGACCGATGGACTCGCGTTCAACGCCGTGCTCCACCGGCACAAACCAGATCTCTTCAG CTGGGACAGAGTGGTCAAAATGTCCCCAATTGAGAGACTTGAACATGCTTTTAGCAAGG CCCACACTTATTTGGGAATTGAAAAGCTTCTAGATCCTGAAGATGTTGCTGTGCATCTCC CTGACAAGAAATCCATAATTATGTATTTAACGTCTCTGTTTGAGGTGCTTCCTCAGCAAG TCACGATAGATGCCATCCGAGAGGTGGAGACTCTCCCAAGGAAGTATAAGAAAGAATGT GAAGAGGAAGAAATTCATATCCAGAGTGCAGTGCTGGCAGAGGAAGGCCAGAGTCCCC GAGCTGAGACCCCTAGCACCGTCACTGAAGTGGACATGGATTTGGACAGCTACCAGATA GCGCTAGAGGAAGTGCTGACGTGGCTGGTATTGATCGACCAAATGCTGAAGTCCAACAT TGTCACTGTGGGGGACGTGAAAGAGATCAATAAGACAGTTTCCCGGATGAAAATCACAA AGGCTGATTTAGAACAACGCCAGAGCAGCGTGGGGAGCGTCCTGCAGGCTGGCAACCAG CTGATGACACAAGGGACTCTGTCAGAGGAGGAGGAGTTTGAGATCCAGGAACAGATGAC CTTGCTGAATGCAAGGTGGGAGAGTACTCAGCATGGTGTGGAGCTGCGGCGGCAGCAGC TGGAGGACATGGTTGTGGACAGCCTGCAGTGGGACGACCACAGGGAAGAGACTGAAGA GCTCATGAGAAAATACGAGGCTCGCTTCTACATGCTGCAGCAGGCCCGCCGGGACCCAC TTAGCAAACAAGTTTCTGATAATCAACTATTGCTTCAAGAGCTGGGGTCTGGCGATGGTG TCATCATGGCGTTTGATAATGTCCTGCAGAAACTTCTGGAAGAATACAGTGGCGATGACA CAAGGAATGTGGAAGAAACCACGGAGTACTTGAAAACATCATGGGTCAATCTCAAACAA AGCATCGCTGATAGACAGAGTGCCTTGGAGGCTGAGCTACAGACAGTGCAGACTTCTCG TAGAGACCTGGAGAACTTTGTCAAGTGGCTTCAGGAAGCAGAAACCACAGCAAATGTGC TGGCCGATGCCTCTCAGCGGGAGAATGCTCTTCAGGACAGTGTCCTGGCCCGGCAGCTCC 49Attorney Docket No: 046192-000119WOPT GACAGCAGATGCTGGACATCCAGGCAGAAATTGATGCCCACAATGACATATTTAAAAGC ATCGATGGAAACCGGCAGAAGATGGTGAAAGCTCTGGGGAATTCTGAGGAAGCAACAAT GCTTC AGCATCGACTGGATGACATGAACCAAAGATGGAATGATTTGAAGGCAAAATCTGCTAGC ATCAGGGCCCATTTGGAGGCCAGTGCTGAGAAATGGAACCGGTTGCTGGCATCGCTGGA AGAGCTGATCAAATGGCTCAATATGAAAGATGAGGAGCTTAAGAAGCAGATGCCCATTG GAGGGGACGTCCCTGCCTTACAGCTCCAGTATGACCACTGCAAGGTGCTGAGACGTGAG CTAA AGGAGAAAGAGTATTCTGTGCTGAACGCCGTAGATCAAGCTCGAGTTTTTCTGGCTGATC AGCCAATAGAGGCCCCCGAAGAACCAAGAAGAAACCCACAATCAAAGACAGAGTTGAC TCCTGAGGAGAGAGCCCAGAAGATCGCCAAAGCCATGCGCAAGCAGTCTTCTGAAGTCC GAGAGAAGTGGGAAAATCTAAATGCTGTCACTAGCAACTGGCAAAAGCAAGTAGGGAA GGCGTTAGAGAAACTCCGAGACCTGCAGGGAGCTATGGACGACCTGGACGCAGACATGA AGGAGGTGGAGGCTGTGCGGAATGGCTGGAAGCCCGTGGGAGACCTGCTTATAGACTCC CTGCAGGATCACATCGAGAAAACCCTGGCGTTTAGAGAAGAAATTGCACCAATCAACTT AAAAGTAAAAACAATGAATGACCTGTCCAGTCAGCTGTCTCCACTTGACTTGCATCCATC TCTAAAGATGTCTCGCCAGCTGGATGACCTTAATATGCGATGGAAACTTCTACAGGTTTC CGTGGACGATCGCCTTAAGCAGCTCCAGGAAGCCCACAGAGATTTTGGGCCATCTTCTCA ACACTTTCTGTCCACTTCAGTCCAGCTGCCGTGGCAGAGATCCATTTCACATAATAAAGT GCCCTATTACATCAACCATCAAACACAGACAACCTGTTGGGATCATCCTAAAATGACTGA GCTCTTCCAATCCCTTGCTGATCTGAATAATGTACGTTTCTCTGCCTACCGCACAGCAATC AAAATTCGAAGGCTGCAAAAAGCATTATGTCTGGATCTCTTAGAGCTGAATACGACGAA TGAAGTTTTCAAGCAGCACAAACTGAACCAAAATGATCAGCTCCTGAGTGTCCCAGACG TCATCAACTGTCTGACCACCACTTACGATGGGCTTGAGCAGCTGCACAAGGACTTGGTCA ATGTTCCACTCTGCGTCGATATGTGTCTCAACTGGCTGCTCAACGTATACGACACGGGCC GGACTGGAAAAATTCGGGTACAGAGTCTGAAGATTGGATTGATGTCTCTCTCCAAAGGC CTCTTAGAAGAGAAATACAGATGTCTCTTTAAGGAGGTGGCAGGGCCAACAGAGATGTG TGACCAGCGGCAGCTTGGCCTGCTACTTCACGATGCCATCCAGATCCCTAGGCAGCTGGG GGAAGTAGCAGCCTTTGGGGGCAGTAACATTGAGCCCAGTGTCCGCAGCTGCTTCCAGC AGAATAACAACAAGCCAGAAATCAGTGTGAAGGAGTTTATAGACTGGATGCATTTGGAA CCCCAGTCCATGGTGTGGTTGCCGGTTCTGCATCGGGTCGCAGCTGCTGAGACTGCAAAA CATCAGGCCAAATGCAACATCTGCAAAGAATGCCCGATTGTTGGGTTCAGATACAGGAG CCTAAAGCATTTTAATTATGATGTCTGCCAGAGTTGCTTCTTTTCTGGAAGAACAGCAAA GGGCCACAAGTTACATTACCCGATGGTAGAATACTGCATACCGACAACATCTGGGGAAG ATGTGAGAGATTTCACTAAGGTGCTGAAGAACAAGTTCAGGTCCAAGAAATATTT 50Attorney Docket No: 046192-000119WOPT TGCCAAACATCCTCGGCTTGGCTACCTGCCTGTCCAGACCGTGCTGGAAGGGGACAACTT AGAAACTCAGGCAATGTGA

[0139] SEQ ID NO: 602atgctttggtgggaggaagtggaggactgctacgagagagaggacgtgcagaagaaaaccttcaccaagtgggtgaacgc 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 aggaactgcaggaagccaccgacgagctggacctgaagctgagacaggccgaagtgatcaagggcagctggcagcctgtg 51Attorney Docket No: 046192-000119WOPT ggcgatctgctgatcgactccctgcaggatcacctggagaaagtgaaggccctgcggggcgagatcgcccccctgaagga gaatgtgagccacgtgaacgacctggccagacagctgaccaccctgggcatccagctgagcccctacaacctgagcacac tggaggatctgaacacccggtggaaactgctgcaggtggccgtggaggatagagtgaggcagctgcacgaagcccacaga gacttcggccctgcctcccagcacttcctgagcaccagcgtgcagggcccctgggagagagccatctcccccaacaaagt gccctactacatcaaccacgagacccagaccacctgctgggaccaccctaagatgaccgagctgtatcagagcctggccg acctgaacaatgtgcggttcagcgcctacagaaccgccatgaagctgcggagactgcagaaggccctgtgcctggatctg ctgagcctgagcgccgcctgcgacgccctggaccagcacaacctgaagcagaatgaccagcccatggacatcctgcagat catcaactgcctgaccacaatctacgaccggctggaacaggagcacaacaacctggtgaatgtgcccctgtgcgtggaca tgtgcctgaattggctgctgaacgtgtacgacaccggcaggaccggcagaatccgcgtgctgagcttcaagaccggcatc atcagcctgtgcaaggcccacctggaggataagtaccgctacctgttcaagcaggtggccagcagcaccggcttctgcga tcagaggagactgggcctgctgctgcacgatagcatccagatccctaggcagctgggcgaagtggccagctttggcggca gcaacatcgagccctctgtgaggagctgcttccagttcgccaacaacaagcccgagatcgaggccgccctgttcctggac tggatgaggctggagcctcagagcatggtgtggctgcctgtgctgcacagagtggccgccgccgagaccgccaagcacca ggccaagtgcaatatctgcaaggagtgccccatcatcggcttccggtacaggagcctgaagcacttcaactacgacatct gccagagctgctttttcagcggcagagtggccaagggccacaaaatgcactaccccatggtggagtactgcacccccacc acctccggcgaggatgtgagagacttcgccaaagtgctgaagaataagttccggaccaagcggtactttgccaagcaccc caggatgggctacctgcccgtgcagaccgtgctggaaggcgacaacatgg

[0140] SEQ ID NO: 603ATGCTGTGGTGGGAGGAGGTGGAGGATTGTTATGAAAGGGAGGACGTGCAGAAGAAGA CTTTTACCAAGTGGGTGAACGCTCAGTTCAGCAAATTTGGGAAGCAGCACATCGAGAAT CTGTTTTCCGACCTGCAGGATGGGAGACGGCTGCTGGATCTGCTGGAAGGACTGACTGGC CAGAAGCTGCCCAAAGAGAAGGGGAGCACTAGGGTGCACGCCCTGAACAACGTGAACA AAGCTCTGAGAGTGCTGCAGAACAACAACGTGGATCTGGTGAATATTGGCAGTACTGAT ATCGTGGACGGGAACCACAAACTGACACTGGGCCTGATCTGGAACATTATTCTGCACTG GCAGGTGAAAAATGTGATGAAGAACATCATGGCCGGGCTGCAGCAGACCAATTCCGAGA AGATCCTGCTGTCTTGGGTGCGGCAGAGCACCCGCAACTATCCCCAGGTGAACGTGATTA ACTTCACTACATCCTGGAGCGACGGGCTGGCCCTGAATGCTCTGATTCACAGCCACAGGC CTGATCTGTTCGACTGGAATAGCGTGGTGTGCCAGCAGTCTGCCACACAGCGCCTGGAAC ATGCCTTCAATATCGCTCGGTACCAGCTGGGGATCGAAAAACTGCTGGACCCAGAGGAT GTGGACACTACATACCCAGATAAAAAGTCTATTCTGATGTACATTACTAGCCTGTTCCAG GTGCTGCCACAGCAGGTGTCTATTGAAGCCATTCAGGAGGTGGAAATGCTGCCCCGCCCC CCCAAAGTGACTAAAGAGGAGCATTTTCAGCTGCATCATCAGATGCATTACAGCCAGCA GATTACCGTGAGCCTGGCTCAGGGATATGAGCGCACCAGTAGTCCAAAACCACGGTTCA AGTCCTACGCTTATACCCAGGCTGCCTACGTGACAACTAGCGACCCTACTAGATCCCCCT TTCCATCCCAGCACCTGGAGGCCCCAGAGGACAAGAGCTTTGGGTCCAGCCTGATGGAA AGCGAGGTGAATCTGGATCGGTACCAGACAGCCCTGGAGGAGGTGCTGAGCTGGCTGCT 52Attorney Docket No: 046192-000119WOPT GAGTGCTGAAGACACACTGCAGGCCCAGGGCGAAATTTCCAATGACGTGGAAGTGGTGA AGGATCAGTTCCACACACACGAGGGCTATATGATGGACCTGACAGCTCACCAGGGGCGC GTGGGCAATATCCTGCAGCTGGGCTCTAAACTGATCGGCACCGGGAAACTGAGTGAGGA CGAGGAAACAGAAGTGCAGGAGCAGATGAACCTGCTGAACAGCCGCTGGGAGTGTCTG AGAGTGGCTAGTATGGAGAAGCAGTCCAACCTGCACCGGGTGCTGATGGACCTGCAGAA CCAGAAACTGAAAGAGCTGAACGACTGGCTGACAAAGACTGAGGAACGCACAAGGAAG ATGGAGGAGGAGCCACTGGGACCCGACCTGGAGGATCTGAAGAGACAGGTGCAGCAGC ATAAGGTGCTGCAGGAGGATCTGGAACAGGAGCAGGTGCGGGTGAACTCCCTGACACAT ATGGTGGTGGTGGTGGACGAATCTAGTGGAGATCACGCCACCGCCGCCCTGGAGGAACA GCTGAAGGTGCTGGGGGACCGGTGGGCCAACATTTGCCGGTGGACCGAGGACAGGTGGG TGCTGCTGCAGGACATCCTGCTGAAATGGCAGAGGCTGACCGAGGAGCAGTGTCTGTTT AGTGCTTGGCTGAGCGAGAAAGAGGACGCCGTGAACAAGATCCACACAACCGGCTTTAA GGATCAGAACGAAATGCTGTCTAGCCTGCAGAAACTGGCTGTGCTGAAGGCCGATCTGG AGAAAAAGAAGCAGAGCATGGGCAAACTGTATAGCCTGAAACAGGACCTGCTGAGCAC CCTGAAGAACAAGAGCGTGACCCAGAAGACAGAAGCCTGGCTGGATAACTTTGCCCGCT GCTGGGACAACCTGGTGCAGAAACTGGAGAAAAGTACAGCTCAGATCTCTCAGGCTGTG ACCACAACCCAGCCTAGCCTGACCCAGACAACCGTGATGGAAACCGTGACCACCGTGAC AACCCGCGAACAGATCCTGGTGAAACATGCCCAGGAAGAGCTGCCACCTCCACCTCCCC AGAAGAAGAGAACCCTGGAGCGGCTGCAGGAGCTGCAGGAAGCCACTGACGAACTGGA CCTGAAGCTGAGGCAGGCCGAAGTGATTAAGGGGTCTTGGCAGCCTGTGGGCGATCTGC TGATTGATTCCCTGCAGGACCACCTGGAAAAGGTGAAGGCTCTGAGAGGCGAAATTGCT CCACTGAAGGAGAACGTGAGTCATGTGAACGATCTGGCTAGACAGCTGACAACACTGGG CATCCAGCTGAGCCCATACAATCTGAGCACACTGGAGGACCTGAATACCAGGTGGAAGC TGCTGCAGGTGGCTGTGGAAGACCGGGTGCGGCAGCTGCATGAGGCCCATCGCGACTTC GGACCAGCCAGCCAGCACTTTCTGAGCACATCCGTGCAGGGGCCCTGGGAGAGGGCCAT TTCTCCCAACAAGGTGCCCTACTATATTAATCACGAGACCCAGACCACTTGTTGGGACCA TCCCAAGATGACAGAACTGTACCAGTCCCTGGCCGATCTGAACAACGTGAGGTTTAGCG CTTACAGAACCGCTATGAAGCTGAGACGGCTGCAGAAGGCCCTGTGCCTGGATCTGCTGT CCCTGTCCGCCGCCTGCGATGCCCTGGATCAGCATAATCTGAAGCAGAACGATCAGCCA ATGGATATCCTGCAGATCATCAACTGCCTGACCACTATCTACGACAGGCTGGAGCAGGA GCACAACAACCTGGTGAACGTGCCTCTGTGCGTGGATATGTGCCTGAACTGGCTGCTGAA CGTGTATGACACTGGGCGCACCGGCCGGATCAGAGTGCTGAGTTTTAAAACTGGGATTAT CTCCCTGTGTAAGGCCCACCTGGAGGACAAGTACAGGTACCTGTTCAAGCAGGTGGCTA GTAGCACTGGATTTTGTGACCAGCGCCGCCTGGGACTGCTGCTGCATGATAGTATCCAGA TTCCTAGACAGCTGGGAGAGGTGGCTAGTTTCGGAGGATCTAACATCGAACCCAGCGTG CGCAGCTGTTTCCAGTTTGCCAATAACAAACCTGAAATCGAGGCTGCTCTGTTCCTGGAT 53Attorney Docket No: 046192-000119WOPT TGGATGCGCCTGGAACCACAGAGCATGGTGTGGCTGCCTGTGCTGCACAGAGTGGCTGC CGCCGAAACTGCCAAGCACCAGGCTAAATGCAACATCTGCAAGGAATGTCCCATTATCG GCTTTCGCTACAGGAGTCTGAAACATTTTAACTACGATATTTGCCAGAGCTGCTTCTTTTC CGGAAGAGTGGCCAAAGGACACAAGATGCACTACCCTATGGTGGAATATTGCACCCCAA CTACATCTGGCGAAGATGTGCGCGATTTTGCCAAGGTGCTGAAGAATAAGTTTCGGACTA AGAGGTACTTCGCCAAGCACCCCCGCATGGGGTATCTGCCAGTGCAGACAGTGCTGGAA GGAGACAATATGGAGACCGATACAATGTGA

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

[0142] In some embodiments of any of the aspects, the polypeptide does not comprise thesequence 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 the 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 ANICRWTEDRWVLLQDQPDLAPGLTTIGASPTQTVTLVTQPVVTKETAISKLEMPSSLML EVPTHRLLQQFPLDLEKFLAWLTEAETTANVLQDATRKERLLEDSKGVKELMKQWQDLQG EIEAHTDVYHNLDENSQKILRSLEGSDDAVLLQRRLDNMNFKWSELRKKSLNIRSHLEAS SDQWKRLHLSLQELLVWLQLKDDELSRQAPIGGDFPAVQKQNDVHRAFKRELKTKEPVIM STLETVRIFLTEQPLEGLEKLYQEPRELPPEERAQNVTRLLRKQAEEVNTEWEKLNLHSA DWQRKIDETLERLQELQEATDELDLKLRQAEVIKGSWQPVGDLLIDSLQDHLEKVKALRG EIAPLKENVSHVNDLARQLTTLGIQLSPYNLSTLEDLNTRWKLLQVAVEDRVRQLHEAHR DFGPASQHFLSTSVQGPWERAISPNKVPYYINHETQTTCWDHPKMTELYQSLADLNNVRF SAYRTAMKLRRLQKALCLDLLSLSAACDALDQHNLKQNDQPMDILQIINCLTTIYDRLEQ EHNNLVNVPLCVDMCLNWLLNVYDTGRTGRIRVLSFKTGIISLCKAHLEDKYRYLFKQVA SSTGFCDQRRLGLLLHDSIQIPRQLGEVASFGGSNIEPSVRSCFQFANNKPEIEAALFLD WMRLEPQSMVWLPVLHRVAAAETAKHQAKCNICKECPIIGFRYRSLKHFNYDICQSCFFS 54Attorney Docket No: 046192-000119WOPT GRVAKGHKMHYPMVEYCTPTTSGEDVRDFAKVLKNKFRTKRYFAKHPRMGYLPVQTVLEG DNMET

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

[0145] SEQ ID NO: 606MLWWEEVEDCYEREDVQKKTFTKWVNAQFSKFGKQHIENLFSDLQDGRRLLDLLEGLTGQ KLPKEKGSTRVHALNNVNKALRVLQNNNVDLVNIGSTDIVDGNHKLTLGLIWNIILHWQV KNVMKNIMAGLQQTNSEKILLSWVRQSTRNYPQVNVINFTTSWSDGLALNALIHSHRPDL FDWNSVVCQQSATQRLEHAFNIARYQLGIEKLLDPEDVDTTYPDKKSILMYITSLFQVLP QQVSIEAIQEVEMLPRPPKVTKEEHFQLHHQMHYSQQITVSLAQGYERTSSPKPRFKSYA YTQAAYVTTSDPTRSPFPSQHLEAPEDKSFGSSLMESEVNLDRYQTALEEVLSWLLSAED TLQAQGEISNDVEVVKDQFHTHEGYMMDLTAHQGRVGNILQLGSKLIGTGKLSEDEETEV QEQMNLLNSRWECLRVASMEKQSNLHRVLMDLQNQKLKELNDWLTKTEERTRKMEEEPLG PDLEDLKRQVQQHKVLQEDLEQEQVRVNSLTHMVVVVDESSGDHATAALEEQLKVLGDRW ANICRWTEDRWVLLQDQPDLAPGLTTIGASPTQTVTLVTQPVVTKETAISKLEMPSSLML EVPTHRLLQQFPLDLEKFLAWLTEAETTANVLQDATRKERLLEDSKGVKELMKQWQDLQG 55Attorney Docket No: 046192-000119WOPT EIEAHTDVYHNLDENSQKILRSLEGSDDAVLLQRRLDNMNFKWSELRKKSLNIRSHLEAS SDQWKRLHLSLQELLVWLQLKDDELSRQAPIGGDFPAVQKQNDVHRAFKRELKTKEPVIM STLETVRIFLTEQPLEGLEKLYQEPRELPPEERAQNVTRLLRKQAEEVNTEWEKLNLHSA DWQRKIDETLERLQELQEATDELDLKLRQAEVIKGSWQPVGDLLIDSLQDHLEKVKALRG EIAPLKENVSHVNDLARQLTTLGIQLSPYNLSTLEDLNTRWKLLQVAVEDRVRQLHEAHR DFGPASQHFLSTSVQGPWERAISPNKVPYYINHETQTTCWDHPKMTELYQSLADLNNVRF SAYRTAMKLRRLQKALCLDLLSLSAACDALDQHNLKQNDQPMDILQIINCLTTIYDRLEQ EHNNLVNVPLCVDMCLNWLLNVYDTGRTGRIRVLSFKTGIISLCKAHLEDKYRYLFKQVA SSTGFCDQRRLGLLLHDSIQIPRQLGEVASFGGSNIEPSVRSCFQFANNKPEIEAALFLD WMRLEPQSMVWLPVLHRVAAAETAKHQAKCNICKECPIIGFRYRSLKHFNYDICQSCFFS GRVAKGHKMHYPMVEYCTPTTSGEDVRDFAKVLKNKFRTKRYFAKHPRMGYLPVQTVLEG DNM

[0146] SEQ ID NO: 607MLWWEEVEDCYEREDVQKKTFTKWVNAQFSKFGKQHIENLFSDLQDGRRLLDLLEGLTGQ KLPKEKGSTRVHALNNVNKALRVLQNNNVDLVNIGSTDIVDGNHKLTLGLIWNIILHWQV KNVMKNIMAGLQQTNSEKILLSWVRQSTRNYPQVNVINFTTSWSDGLALNALIHSHRPDL FDWNSVVCQQSATQRLEHAFNIARYQLGIEKLLDPEDVDTTYPDKKSILMYITSLFQVLP QQVSIEAIQEVEMLPRPPKVTKEEHFQLHHQMHYSQQITVSLAQGYERTSSPKPRFKSYA YTQAAYVTTSDPTRSPFPSQHLEAPEDKSFGSSLMESEVNLDRYQTALEEVLSWLLSAED TLQAQGEISNDVEVVKDQFHTHEGYMMDLTAHQGRVGNILQLGSKLIGTGKLSEDEETEV QEQMNLLNSRWECLRVASMEKQSNLHRVLMDLQNQKLKELNDWLTKTEERTRKMEEEPLG PDLEDLKRQVQQHKVLQEDLEQEQVRVNSLTHMVVVVDESSGDHATAALEEQLKVLGDRW ANICRWTEDRWVLLQDILLKWQRLTEEQCLFSAWLSEKEDAVNKIHTTGFKDQNEMLSSL QKLAVLKADLEKKKQSMGKLYSLKQDLLSTLKNKSVTQKTEAWLDNFARCWDNLVQKLE K STAQISQAVTTTQPSLTQTTVMETVTTVTTREQILVKHAQEELPPPPPQKKRTLERLQEL QEATDELDLKLRQAEVIKGSWQPVGDLLIDSLQDHLEKVKALRGEIAPLKENVSHVNDLA RQLTTLGIQLSPYNLSTLEDLNTRWKLLQVAVEDRVRQLHEAHRDFGPASQHFLSTSVQG PWERAISPNKVPYYINHETQTTCWDHPKMTELYQSLADLNNVRFSAYRTAMKLRRLQKAL CLDLLSLSAACDALDQHNLKQNDQPMDILQIINCLTTIYDRLEQEHNNLVNVPLCVDMCL NWLLNVYDTGRTGRIRVLSFKTGIISLCKAHLEDKYRYLFKQVASSTGFCDQRRLGLLLH DSIQIPRQLGEVASFGGSNIEPSVRSCFQFANNKPEIEAALFLDWMRLEPQSMVWLPVLH RVAAAETAKHQAKCNICKECPIIGFRYRSLKHFNYDICQSCFFSGRVAKGHKMHYPMVEY CTPTTSGEDVRDFAKVLKNKFRTKRYFAKHPRMGYLPVQTVLEGDNMETDTM

[0147] In one aspect of any of the embodiments, described herein is a polypeptide comprising autrophin N-terminal portion and a dystrophin C-terminal portion. In one aspect of any of the 56Attorney Docket No: 046192-000119WOPT embodiments, described herein is a polypeptide comprising a dystrophin N-terminal portion and a utrophin C-terminal portion.

[0148] In one aspect of any of the the embodiments, described herein is a microutrophinpolypeptide 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 microutrophinpolypeptide 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 furthercomprises 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 polypeptide furthercomprises 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 furthercomprises 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, theutrophin 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 domain 57Attorney Docket No: 046192-000119WOPT 4, the utrophin SLR22 domain, and the utrophin CR domain are encoded by a codon optimized nucleic acid sequence.

[0154] In some embodiments of any of the aspects, the microutrophin polypeptide is encoded bya 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 moleculecomprising 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 moleculecomprising 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 identity 58Attorney Docket No: 046192-000119WOPT 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 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 moleculeconsisting 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 moleculecomprising 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 one 59Attorney Docket No: 046192-000119WOPT 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. 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 moleculecomprising 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 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: 100-109 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 moleculeconsisting 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, 60Attorney Docket No: 046192-000119WOPT 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 moleculecomprising 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 moleculeconsisting 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 moleculecomprising 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 sequence 61Attorney Docket No: 046192-000119WOPT 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 comprising 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 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 moleculeconsisting 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 moleculecomprising 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. 62Attorney Docket No: 046192-000119WOPT

[0167] In one aspect of any of the embodiments, described herein is a nucleic acid moleculeconsisting 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 moleculecomprising 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 moleculeconsisting 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 SEQ 63Attorney Docket No: 046192-000119WOPT ID 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 moleculecomprising 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 moleculeconsisting 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 moleculecomprising 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 SEQ 64Attorney Docket No: 046192-000119WOPT ID 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 moleculeconsisting 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 moleculecomprising 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 moleculeconsisting 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 SEQ 65Attorney Docket No: 046192-000119WOPT ID 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 asequence 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 hereindoes 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 AGAGCCTGCAGAAGCTGCTGGAGGAGCACAAGAGCCTGCAGAGCGACCTGGAGGCCGAGCAGGTGAAG 66Attorney Docket No: 046192-000119WOPT GTGAACAGCCTGACCCACATGGTGGTGATCGTGGACGAGAACAGCGGCGAGAGCGCCACCGCCATCCT GGAGGACCAGCTGCAGAAGCTGGGCGAGCGGTGGACCGCCGTGTGCCGGTGGACCGAGGAGCGGTGGA ACCGGCTGCAGGAGATCAACATCCTGTGGCAGGAGCTGCTGGAGGAGCAGTGCCTGCTGAAGGCCTGG CTGACCGAGAAGGAGGAGGCCCTGAACAAGGTGCAGACCAGCAACTTCAAGGACCAGAAGGAGCTGAG CGTGAGCGTGCGGCGGCTGGCCATCCTGAAGGAGGACATGGAGATGAAGCGGCAGACCCTGGACCAGC TGAGCGAGATCGGCCAGGACGTGGGCCAGCTGCTGGACAACAGCAAGGCCAGCAAGAAGATCAACAGC GACAGCGAGGAGCTGACCCAGCGGTGGGACAGCCTGGTGCAGCGGCTGGAGGACAGCAGCAACCAGGT GACCCAGGCCGTGGCCAAGCTGGGCATGAGCCAGATCCCCCAGAAGGACCTGCTGGAGACCGTGCGGG TGCGGGAGCAGGCCATCACCAAGAAGAGCAAGCAGGAGCTGCCCCCCCCCCCCCCCCCCAAGAAGCGG CAGATCCACGTGGACCTGGAGAAGCTGCGGGACCTGCAGGGCGCCATGGACGACCTGGACGCCGACAT GAAGGAGGCCGAGAGCGTGCGGAACGGCTGGAAGCCCGTGGGCGACCTGCTGATCGACAGCCTGCAGG ACCACATCGAGAAGATCATGGCCTTCCGGGAGGAGATCGCCCCCATCAACTTCAAGGTGAAGACCGTG AACGACCTGAGCAGCCAGCTGAGCCCCCTGGACCTGCACCCCAGCCTGAAGATGAGCCGGCAGCTGGA CGACCTGAACATGCGGTGGAAGCTGCTGCAGGTGAGCGTGGACGACCGGCTGAAGCAGCTGCAGGAGG CCCACCGGGACTTCGGCCCCAGCAGCCAGCACTTCCTGAGCACCAGCGTGCAGCTGCCCTGGCAGCGG AGCATCAGCCACAACAAGGTGCCCTACTACATCAACCACCAGACCCAGACCACCTGCTGGGACCACCC CAAGATGACCGAGCTGTTCCAGAGCCTGGCCGACCTGAACAACGTGCGGTTCAGCGCCTACCGGACCG CCATCAAGATCCGGCGGCTGCAGAAGGCCCTGTGCCTGGACCTGCTGGAGCTGAGCACCACCAACGAG ATCTTCAAGCAGCACAAGCTGAACCAGAACGACCAGCTGCTGAGCGTGCCCGACGTGATCAACTGCCT GACCACCACCTACGACGGCCTGGAGCAGATGCACAAGGACCTGGTGAACGTGCCCCTGTGCGTGGACA TGTGCCTGAACTGGCTGCTGAACGTGTACGACACCGGCCGGACCGGCAAGATCCGGGTGCAGAGCCTG AAGATCGGCCTGATGAGCCTGAGCAAGGGCCTGCTGGAGGAGAAGTACCGGTACCTGTTCAAGGAGGT GGCCGGCCCCACCGAGATGTGCGACCAGCGGCAGCTGGGCCTGCTGCTGCACGACGCCATCCAGATCC CCCGGCAGCTGGGCGAGGTGGCCGCCTTCGGCGGCAGCAACATCGAGCCCAGCGTGCGGAGCTGCTTC CAGCAGAACAACAACAAGCCCGAGATCAGCGTGAAGGAGTTCATCGACTGGATGCACCTGGAGCCCCA GAGCATGGTGTGGCTGCCCGTGCTGCACCGGGTGGCCGCCGCCGAGACCGCCAAGCACCAGGCCAAGT GCAACATCTGCAAGGAGTGCCCCATCGTGGGCTTCCGGTACCGGAGCCTGAAGCACTTCAACTACGAC GTGTGCCAGAGCTGCTTCTTCAGCGGCCGGACCGCCAAGGGCCACAAGCTGCACTACCCCATGGTGGA GTACTGCATCCCCACCACCAGCGGCGAGGACGTGCGGGACTTCACCAAGGTGCTGAAGAACAAGTTCC GGAGCAAGAAGTACTTCGCCAAGCACCCCCGGCTGGGCTACCTGCCCGTGCAGACCGTGCTGGAGGGC GACAACCTGGAGACCCAGGCCATGTGA

[0179] G4 (SEQ ID NO: 101)ATGGCCAAGTACGGCGAGCACGAGGCCTCCCCCGACAACGGCCAGAACGAGTTCTCCGACATCATCAA GTCCCGCTCCGACGAGCACAACGACGTGCAGAAGAAGACCTTCACCAAGTGGATCAACGCCCGCTTCT CCAAGTCCGGCAAGCCCCCCATCAACGACATGTTCACCGACCTGAAGGACGGCCGCAAGCTGCTGGAC CTGCTGGAGGGCCTGACCGGCACCTCCCTGCCCAAGGAGCGCGGCTCCACCCGCGTGCACGCCCTGAA CAACGTGAACCGCGTGCTGCAGGTGCTGCACCAGAACAACGTGGAGCTGGTGAACATCGGCGGCACCG ACATCGTGGACGGCAACCACAAGCTGACCCTGGGCCTGCTGTGGTCCATCATCCTGCACTGGCAGGTG AAGGACGTGATGAAGGACGTGATGTCCGACCTGCAGCAGACCAACTCCGAGAAGATCCTGCTGTCCTG GGTGCGCCAGACCACCCGCCCCTACTCCCAGGTGAACGTGCTGAACTTCACCACCTCCTGGACCGACG GCCTGGCCTTCAACGCCGTGCTGCACCGCCACAAGCCCGACCTGTTCTCCTGGGACAAGGTGGTGAAG ATGTCCCCCATCGAGCGCCTGGAGCACGCCTTCTCCAAGGCCCAGACCTACCTGGGCATCGAGAAGCT GCTGGACCCCGAGGACGTGGCCGTGCAGCTGCCCGACAAGAAGTCCATCATCATGTACCTGACCTCCC TGTTCGAGGTGCTGCCCCAGCAGGTGACCATCGACGCCATCCGCGAGGTGGAGACCCTGCCCCGCAAG TACAAGAAGGAGTGCGAGGAGGAGGCCATCAACATCCAGTCCACCGCCCCCGAGGAGGAGCACGAGTC CCCCCGCGCCGAGACCCCCTCCACCGTGACCGAGGTGGACATGGACCTGGACTCCTACCAGATCGCCC TGGAGGAGGTGCTGACCTGGCTGCTGTCCGCCGAGGACACCTTCCAGGAGCAGGACGACATCTCCGAC GACGTGGAGGAGGTGAAGGACCAGTTCGCCACCCACGAGGCCTTCATGATGGAGCTGACCGCCCACCA GTCCTCCGTGGGCTCCGTGCTGCAGGCCGGCAACCAGCTGATCACCCAGGGCACCCTGTCCGACGAGG AGGAGTTCGAGATCCAGGAGCAGATGACCCTGCTGAACGCCCGCTGGGAGGCCCTGCGCGTGGAGTCC ATGGACCGCCAGTCCCGCCTGCACGACGTGCTGATGGAGCTGCAGAAGAAGCAGCTGCAGCAGCTGTC CGCCTGGCTGACCCTGACCGAGGAGCGCATCCAGAAGATGGAGACCTGCCCCCTGGACGACGACGTGA AGTCCCTGCAGAAGCTGCTGGAGGAGCACAAGTCCCTGCAGTCCGACCTGGAGGCCGAGCAGGTGAAG 67Attorney Docket No: 046192-000119WOPT GTGAACTCCCTGACCCACATGGTGGTGATCGTGGACGAGAACTCCGGCGAGTCCGCCACCGCCATCCT GGAGGACCAGCTGCAGAAGCTGGGCGAGCGCTGGACCGCCGTGTGCCGCTGGACCGAGGAGCGCTGGA ACCGCCTGCAGGAGATCAACATCCTGTGGCAGGAGCTGCTGGAGGAGCAGTGCCTGCTGAAGGCCTGG CTGACCGAGAAGGAGGAGGCCCTGAACAAGGTGCAGACCTCCAACTTCAAGGACCAGAAGGAGCTGTC CGTGTCCGTGCGCCGCCTGGCCATCCTGAAGGAGGACATGGAGATGAAGCGCCAGACCCTGGACCAGC TGTCCGAGATCGGCCAGGACGTGGGCCAGCTGCTGGACAACTCCAAGGCCTCCAAGAAGATCAACTCC GACTCCGAGGAGCTGACCCAGCGCTGGGACTCCCTGGTGCAGCGCCTGGAGGACTCCTCCAACCAGGT GACCCAGGCCGTGGCCAAGCTGGGCATGTCCCAGATCCCCCAGAAGGACCTGCTGGAGACCGTGCGCG TGCGCGAGCAGGCCATCACCAAGAAGTCCAAGCAGGAGCTGCCCCCCCCCCCCCCCCCCAAGAAGCGC CAGATCCACGTGGACCTGGAGAAGCTGCGCGACCTGCAGGGCGCCATGGACGACCTGGACGCCGACAT GAAGGAGGCCGAGTCCGTGCGCAACGGCTGGAAGCCCGTGGGCGACCTGCTGATCGACTCCCTGCAGG ACCACATCGAGAAGATCATGGCCTTCCGCGAGGAGATCGCCCCCATCAACTTCAAGGTGAAGACCGTG AACGACCTGTCCTCCCAGCTGTCCCCCCTGGACCTGCACCCCTCCCTGAAGATGTCCCGCCAGCTGGA CGACCTGAACATGCGCTGGAAGCTGCTGCAGGTGTCCGTGGACGACCGCCTGAAGCAGCTGCAGGAGG CCCACCGCGACTTCGGCCCCTCCTCCCAGCACTTCCTGTCCACCTCCGTGCAGCTGCCCTGGCAGCGC TCCATCTCCCACAACAAGGTGCCCTACTACATCAACCACCAGACCCAGACCACCTGCTGGGACCACCC CAAGATGACCGAGCTGTTCCAGTCCCTGGCCGACCTGAACAACGTGCGCTTCTCCGCCTACCGCACCG CCATCAAGATCCGCCGCCTGCAGAAGGCCCTGTGCCTGGACCTGCTGGAGCTGTCCACCACCAACGAG ATCTTCAAGCAGCACAAGCTGAACCAGAACGACCAGCTGCTGTCCGTGCCCGACGTGATCAACTGCCT GACCACCACCTACGACGGCCTGGAGCAGATGCACAAGGACCTGGTGAACGTGCCCCTGTGCGTGGACA TGTGCCTGAACTGGCTGCTGAACGTGTACGACACCGGCCGCACCGGCAAGATCCGCGTGCAGTCCCTG AAGATCGGCCTGATGTCCCTGTCCAAGGGCCTGCTGGAGGAGAAGTACCGCTACCTGTTCAAGGAGGT GGCCGGCCCCACCGAGATGTGCGACCAGCGCCAGCTGGGCCTGCTGCTGCACGACGCCATCCAGATCC CCCGCCAGCTGGGCGAGGTGGCCGCCTTCGGCGGCTCCAACATCGAGCCCTCCGTGCGCTCCTGCTTC CAGCAGAACAACAACAAGCCCGAGATCTCCGTGAAGGAGTTCATCGACTGGATGCACCTGGAGCCCCA GTCCATGGTGTGGCTGCCCGTGCTGCACCGCGTGGCCGCCGCCGAGACCGCCAAGCACCAGGCCAAGT GCAACATCTGCAAGGAGTGCCCCATCGTGGGCTTCCGCTACCGCTCCCTGAAGCACTTCAACTACGAC GTGTGCCAGTCCTGCTTCTTCTCCGGCCGCACCGCCAAGGGCCACAAGCTGCACTACCCCATGGTGGA GTACTGCATCCCCACCACCTCCGGCGAGGACGTGCGCGACTTCACCAAGGTGCTGAAGAACAAGTTCC GCTCCAAGAAGTACTTCGCCAAGCACCCCCGCCTGGGCTACCTGCCCGTGCAGACCGTGCTGGAGGGC GACAACCTGGAGACCCAGGCCATGTGA

[0180] G5 (SEQ ID NO: 102)ATGGCCAAGTACGGCGAGCACGAGGCCTCCCCTGACAACGGCCAGAACGAGTTCTCCGACATCATCAA GTCCAGGTCCGACGAGCACAACGACGTGCAGAAGAAGACCTTCACCAAGTGGATCAACGCCAGGTTCT CCAAGTCCGGCAAGCCTCCTATCAACGACATGTTCACCGACCTGAAGGACGGCAGGAAGCTGCTGGAC CTGCTGGAGGGCCTGACCGGCACCTCCCTGCCTAAGGAGAGGGGCTCCACCAGGGTGCACGCCCTGAA CAACGTGAACAGGGTGCTGCAGGTGCTGCACCAGAACAACGTGGAGCTGGTGAACATCGGCGGCACCG ACATCGTGGACGGCAACCACAAGCTGACCCTGGGCCTGCTGTGGTCCATCATCCTGCACTGGCAGGTG AAGGACGTGATGAAGGACGTGATGTCCGACCTGCAGCAGACCAACTCCGAGAAGATCCTGCTGTCCTG GGTGAGGCAGACCACCAGGCCTTACTCCCAGGTGAACGTGCTGAACTTCACCACCTCCTGGACCGACG GCCTGGCCTTCAACGCCGTGCTGCACAGGCACAAGCCTGACCTGTTCTCCTGGGACAAGGTGGTGAAG ATGTCCCCTATCGAGAGGCTGGAGCACGCCTTCTCCAAGGCCCAGACCTACCTGGGCATCGAGAAGCT GCTGGACCCTGAGGACGTGGCCGTGCAGCTGCCTGACAAGAAGTCCATCATCATGTACCTGACCTCCC TGTTCGAGGTGCTGCCTCAGCAGGTGACCATCGACGCCATCAGGGAGGTGGAGACCCTGCCTAGGAAG TACAAGAAGGAGTGCGAGGAGGAGGCCATCAACATCCAGTCCACCGCCCCTGAGGAGGAGCACGAGTC CCCTAGGGCCGAGACCCCTTCCACCGTGACCGAGGTGGACATGGACCTGGACTCCTACCAGATCGCCC TGGAGGAGGTGCTGACCTGGCTGCTGTCCGCCGAGGACACCTTCCAGGAGCAGGACGACATCTCCGAC GACGTGGAGGAGGTGAAGGACCAGTTCGCCACCCACGAGGCCTTCATGATGGAGCTGACCGCCCACCA GTCCTCCGTGGGCTCCGTGCTGCAGGCCGGCAACCAGCTGATCACCCAGGGCACCCTGTCCGACGAGG AGGAGTTCGAGATCCAGGAGCAGATGACCCTGCTGAACGCCAGGTGGGAGGCCCTGAGGGTGGAGTCC ATGGACAGGCAGTCCAGGCTGCACGACGTGCTGATGGAGCTGCAGAAGAAGCAGCTGCAGCAGCTGTC CGCCTGGCTGACCCTGACCGAGGAGAGGATCCAGAAGATGGAGACCTGCCCTCTGGACGACGACGTGA AGTCCCTGCAGAAGCTGCTGGAGGAGCACAAGTCCCTGCAGTCCGACCTGGAGGCCGAGCAGGTGAAG 68Attorney Docket No: 046192-000119WOPT GTGAACTCCCTGACCCACATGGTGGTGATCGTGGACGAGAACTCCGGCGAGTCCGCCACCGCCATCCT GGAGGACCAGCTGCAGAAGCTGGGCGAGAGGTGGACCGCCGTGTGCAGGTGGACCGAGGAGAGGTGGA ACAGGCTGCAGGAGATCAACATCCTGTGGCAGGAGCTGCTGGAGGAGCAGTGCCTGCTGAAGGCCTGG CTGACCGAGAAGGAGGAGGCCCTGAACAAGGTGCAGACCTCCAACTTCAAGGACCAGAAGGAGCTGTC CGTGTCCGTGAGGAGGCTGGCCATCCTGAAGGAGGACATGGAGATGAAGAGGCAGACCCTGGACCAGC TGTCCGAGATCGGCCAGGACGTGGGCCAGCTGCTGGACAACTCCAAGGCCTCCAAGAAGATCAACTCC GACTCCGAGGAGCTGACCCAGAGGTGGGACTCCCTGGTGCAGAGGCTGGAGGACTCCTCCAACCAGGT GACCCAGGCCGTGGCCAAGCTGGGCATGTCCCAGATCCCTCAGAAGGACCTGCTGGAGACCGTGAGGG TGAGGGAGCAGGCCATCACCAAGAAGTCCAAGCAGGAGCTGCCTCCTCCTCCTCCTCCTAAGAAGAGG CAGATCCACGTGGACCTGGAGAAGCTGAGGGACCTGCAGGGCGCCATGGACGACCTGGACGCCGACAT GAAGGAGGCCGAGTCCGTGAGGAACGGCTGGAAGCCTGTGGGCGACCTGCTGATCGACTCCCTGCAGG ACCACATCGAGAAGATCATGGCCTTCAGGGAGGAGATCGCCCCTATCAACTTCAAGGTGAAGACCGTG AACGACCTGTCCTCCCAGCTGTCCCCTCTGGACCTGCACCCTTCCCTGAAGATGTCCAGGCAGCTGGA CGACCTGAACATGAGGTGGAAGCTGCTGCAGGTGTCCGTGGACGACAGGCTGAAGCAGCTGCAGGAGG CCCACAGGGACTTCGGCCCTTCCTCCCAGCACTTCCTGTCCACCTCCGTGCAGCTGCCTTGGCAGAGG TCCATCTCCCACAACAAGGTGCCTTACTACATCAACCACCAGACCCAGACCACCTGCTGGGACCACCC TAAGATGACCGAGCTGTTCCAGTCCCTGGCCGACCTGAACAACGTGAGGTTCTCCGCCTACAGGACCG CCATCAAGATCAGGAGGCTGCAGAAGGCCCTGTGCCTGGACCTGCTGGAGCTGTCCACCACCAACGAG ATCTTCAAGCAGCACAAGCTGAACCAGAACGACCAGCTGCTGTCCGTGCCTGACGTGATCAACTGCCT GACCACCACCTACGACGGCCTGGAGCAGATGCACAAGGACCTGGTGAACGTGCCTCTGTGCGTGGACA TGTGCCTGAACTGGCTGCTGAACGTGTACGACACCGGCAGGACCGGCAAGATCAGGGTGCAGTCCCTG AAGATCGGCCTGATGTCCCTGTCCAAGGGCCTGCTGGAGGAGAAGTACAGGTACCTGTTCAAGGAGGT GGCCGGCCCTACCGAGATGTGCGACCAGAGGCAGCTGGGCCTGCTGCTGCACGACGCCATCCAGATCC CTAGGCAGCTGGGCGAGGTGGCCGCCTTCGGCGGCTCCAACATCGAGCCTTCCGTGAGGTCCTGCTTC CAGCAGAACAACAACAAGCCTGAGATCTCCGTGAAGGAGTTCATCGACTGGATGCACCTGGAGCCTCA GTCCATGGTGTGGCTGCCTGTGCTGCACAGGGTGGCCGCCGCCGAGACCGCCAAGCACCAGGCCAAGT GCAACATCTGCAAGGAGTGCCCTATCGTGGGCTTCAGGTACAGGTCCCTGAAGCACTTCAACTACGAC GTGTGCCAGTCCTGCTTCTTCTCCGGCAGGACCGCCAAGGGCCACAAGCTGCACTACCCTATGGTGGA GTACTGCATCCCTACCACCTCCGGCGAGGACGTGAGGGACTTCACCAAGGTGCTGAAGAACAAGTTCA GGTCCAAGAAGTACTTCGCCAAGCACCCTAGGCTGGGCTACCTGCCTGTGCAGACCGTGCTGGAGGGC GACAACCTGGAGACCCAGGCCATGTGA

[0181] G6 (SEQ ID NO: 103)ATGGCCAAGTACGGCGAGCACGAGGCCTCCCCCGACAACGGCCAGAACGAGTTCTCCGACATCATCAA GTCCAGGTCCGACGAGCACAACGACGTGCAGAAGAAGACCTTCACCAAGTGGATCAACGCCAGGTTCT CCAAGTCCGGCAAGCCCCCCATCAACGACATGTTCACCGACCTGAAGGACGGCAGGAAGCTGCTGGAC CTGCTGGAGGGCCTGACCGGCACCTCCCTGCCCAAGGAGAGGGGCTCCACCAGGGTGCACGCCCTGAA CAACGTGAACAGGGTGCTGCAGGTGCTGCACCAGAACAACGTGGAGCTGGTGAACATCGGCGGCACCG ACATCGTGGACGGCAACCACAAGCTGACCCTGGGCCTGCTGTGGTCCATCATCCTGCACTGGCAGGTG AAGGACGTGATGAAGGACGTGATGTCCGACCTGCAGCAGACCAACTCCGAGAAGATCCTGCTGTCCTG GGTGAGGCAGACCACCAGGCCCTACTCCCAGGTGAACGTGCTGAACTTCACCACCTCCTGGACCGACG GCCTGGCCTTCAACGCCGTGCTGCACAGGCACAAGCCCGACCTGTTCTCCTGGGACAAGGTGGTGAAG ATGTCCCCCATCGAGAGGCTGGAGCACGCCTTCTCCAAGGCCCAGACCTACCTGGGCATCGAGAAGCT GCTGGACCCCGAGGACGTGGCCGTGCAGCTGCCCGACAAGAAGTCCATCATCATGTACCTGACCTCCC TGTTCGAGGTGCTGCCCCAGCAGGTGACCATCGACGCCATCAGGGAGGTGGAGACCCTGCCCAGGAAG TACAAGAAGGAGTGCGAGGAGGAGGCCATCAACATCCAGTCCACCGCCCCCGAGGAGGAGCACGAGTC CCCCAGGGCCGAGACCCCCTCCACCGTGACCGAGGTGGACATGGACCTGGACTCCTACCAGATCGCCC TGGAGGAGGTGCTGACCTGGCTGCTGTCCGCCGAGGACACCTTCCAGGAGCAGGACGACATCTCCGAC GACGTGGAGGAGGTGAAGGACCAGTTCGCCACCCACGAGGCCTTCATGATGGAGCTGACCGCCCACCA GTCCTCCGTGGGCTCCGTGCTGCAGGCCGGCAACCAGCTGATCACCCAGGGCACCCTGTCCGACGAGG AGGAGTTCGAGATCCAGGAGCAGATGACCCTGCTGAACGCCAGGTGGGAGGCCCTGAGGGTGGAGTCC ATGGACAGGCAGTCCAGGCTGCACGACGTGCTGATGGAGCTGCAGAAGAAGCAGCTGCAGCAGCTGTC CGCCTGGCTGACCCTGACCGAGGAGAGGATCCAGAAGATGGAGACCTGCCCCCTGGACGACGACGTGA AGTCCCTGCAGAAGCTGCTGGAGGAGCACAAGTCCCTGCAGTCCGACCTGGAGGCCGAGCAGGTGAAG 69Attorney Docket No: 046192-000119WOPT GTGAACTCCCTGACCCACATGGTGGTGATCGTGGACGAGAACTCCGGCGAGTCCGCCACCGCCATCCT GGAGGACCAGCTGCAGAAGCTGGGCGAGAGGTGGACCGCCGTGTGCAGGTGGACCGAGGAGAGGTGGA ACAGGCTGCAGGAGATCAACATCCTGTGGCAGGAGCTGCTGGAGGAGCAGTGCCTGCTGAAGGCCTGG CTGACCGAGAAGGAGGAGGCCCTGAACAAGGTGCAGACCTCCAACTTCAAGGACCAGAAGGAGCTGTC CGTGTCCGTGAGGAGGCTGGCCATCCTGAAGGAGGACATGGAGATGAAGAGGCAGACCCTGGACCAGC TGTCCGAGATCGGCCAGGACGTGGGCCAGCTGCTGGACAACTCCAAGGCCTCCAAGAAGATCAACTCC GACTCCGAGGAGCTGACCCAGAGGTGGGACTCCCTGGTGCAGAGGCTGGAGGACTCCTCCAACCAGGT GACCCAGGCCGTGGCCAAGCTGGGCATGTCCCAGATCCCCCAGAAGGACCTGCTGGAGACCGTGAGGG TGAGGGAGCAGGCCATCACCAAGAAGTCCAAGCAGGAGCTGCCCCCCCCCCCCCCCCCCAAGAAGAGG CAGATCCACGTGGACCTGGAGAAGCTGAGGGACCTGCAGGGCGCCATGGACGACCTGGACGCCGACAT GAAGGAGGCCGAGTCCGTGAGGAACGGCTGGAAGCCCGTGGGCGACCTGCTGATCGACTCCCTGCAGG ACCACATCGAGAAGATCATGGCCTTCAGGGAGGAGATCGCCCCCATCAACTTCAAGGTGAAGACCGTG AACGACCTGTCCTCCCAGCTGTCCCCCCTGGACCTGCACCCCTCCCTGAAGATGTCCAGGCAGCTGGA CGACCTGAACATGAGGTGGAAGCTGCTGCAGGTGTCCGTGGACGACAGGCTGAAGCAGCTGCAGGAGG CCCACAGGGACTTCGGCCCCTCCTCCCAGCACTTCCTGTCCACCTCCGTGCAGCTGCCCTGGCAGAGG TCCATCTCCCACAACAAGGTGCCCTACTACATCAACCACCAGACCCAGACCACCTGCTGGGACCACCC CAAGATGACCGAGCTGTTCCAGTCCCTGGCCGACCTGAACAACGTGAGGTTCTCCGCCTACAGGACCG CCATCAAGATCAGGAGGCTGCAGAAGGCCCTGTGCCTGGACCTGCTGGAGCTGTCCACCACCAACGAG ATCTTCAAGCAGCACAAGCTGAACCAGAACGACCAGCTGCTGTCCGTGCCCGACGTGATCAACTGCCT GACCACCACCTACGACGGCCTGGAGCAGATGCACAAGGACCTGGTGAACGTGCCCCTGTGCGTGGACA TGTGCCTGAACTGGCTGCTGAACGTGTACGACACCGGCAGGACCGGCAAGATCAGGGTGCAGTCCCTG AAGATCGGCCTGATGTCCCTGTCCAAGGGCCTGCTGGAGGAGAAGTACAGGTACCTGTTCAAGGAGGT GGCCGGCCCCACCGAGATGTGCGACCAGAGGCAGCTGGGCCTGCTGCTGCACGACGCCATCCAGATCC CCAGGCAGCTGGGCGAGGTGGCCGCCTTCGGCGGCTCCAACATCGAGCCCTCCGTGAGGTCCTGCTTC CAGCAGAACAACAACAAGCCCGAGATCTCCGTGAAGGAGTTCATCGACTGGATGCACCTGGAGCCCCA GTCCATGGTGTGGCTGCCCGTGCTGCACAGGGTGGCCGCCGCCGAGACCGCCAAGCACCAGGCCAAGT GCAACATCTGCAAGGAGTGCCCCATCGTGGGCTTCAGGTACAGGTCCCTGAAGCACTTCAACTACGAC GTGTGCCAGTCCTGCTTCTTCTCCGGCAGGACCGCCAAGGGCCACAAGCTGCACTACCCCATGGTGGA GTACTGCATCCCCACCACCTCCGGCGAGGACGTGAGGGACTTCACCAAGGTGCTGAAGAACAAGTTCA GGTCCAAGAAGTACTTCGCCAAGCACCCCAGGCTGGGCTACCTGCCCGTGCAGACCGTGCTGGAGGGC GACAACCTGGAGACCCAGGCCATGTGA

[0182] G7 (SEQ ID NO: 104)ATGGCCAAGTATGGGGAGCATGAGGCTAGTCCTGACAATGGGCAGAATGAATTCAGTGACATCATTAA GTCTAGGTCAGATGAGCACAATGATGTACAGAAGAAAACCTTTACTAAATGGATAAATGCCAGGTTTT CAAAGAGTGGGAAACCACCCATCAATGATATGTTCACTGACCTCAAAGATGGCAGGAAGCTATTGGAT CTTCTAGAGGGCCTCACAGGTACATCACTGCCAAAGGAAAGGGGTTCCACAAGAGTACATGCATTAAA TAATGTCAACAGGGTGCTGCAGGTTTTACATCAGAACAATGTGGAATTAGTGAATATAGGAGGAACTG ACATAGTGGATGGAAATCACAAACTGACATTGGGGTTACTTTGGAGCATCATTTTGCACTGGCAGGTG AAAGATGTGATGAAGGATGTCATGTCTGACCTGCAGCAGACCAACTCAGAGAAGATCCTGCTCAGCTG GGTGAGGCAGACTACCAGGCCCTACTCTCAAGTCAATGTGCTCAACTTCACCACCAGCTGGACAGATG GCCTGGCCTTTAATGCAGTGCTCCACAGGCATAAACCTGACCTCTTCAGCTGGGATAAAGTTGTCAAA ATGTCACCAATTGAGAGACTTGAACATGCTTTCAGCAAGGCTCAAACATATTTGGGAATAGAGAAGCT GTTAGATCCTGAAGATGTTGCAGTTCAGCTTCCAGACAAGAAAAGTATAATTATGTATTTAACTAGTT TGTTTGAGGTGCTACCTCAGCAAGTCACCATAGATGCCATCAGGGAGGTAGAGACCCTCCCAAGGAAA TATAAAAAAGAATGTGAGGAAGAGGCTATTAATATACAGAGCACAGCACCTGAGGAGGAGCATGAGAG TCCCAGGGCTGAGACACCTAGCACTGTGACTGAGGTGGACATGGATCTGGATAGCTATCAGATTGCTT TGGAGGAAGTGCTGACCTGGTTGCTTTCTGCAGAAGACACTTTCCAGGAGCAGGATGACATTTCTGAT GATGTTGAAGAAGTCAAAGACCAGTTTGCCACCCATGAGGCATTTATGATGGAACTGACTGCCCACCA GTCCTCTGTGGGCTCTGTGCTGCAGGCAGGCAACCAACTGATAACTCAAGGAACACTGTCAGATGAAG AAGAATTTGAGATTCAGGAACAGATGACACTGCTGAATGCTAGATGGGAGGCCCTTAGGGTGGAGAGC ATGGACAGGCAGTCCAGGCTGCATGATGTCCTGATGGAACTGCAGAAGAAGCAACTGCAGCAGCTCTC TGCATGGTTAACACTCACTGAGGAGAGGATTCAGAAGATGGAAACTTGCCCCCTGGATGATGATGTCA AATCTCTACAAAAGCTGCTAGAAGAACATAAAAGTTTGCAATCTGACCTTGAGGCTGAACAGGTGAAA 70Attorney Docket No: 046192-000119WOPT GTAAATTCACTAACTCACATGGTGGTGATTGTGGATGAGAACAGTGGTGAGAGTGCTACTGCTATCCT AGAAGACCAGTTACAGAAACTTGGAGAGAGGTGGACAGCAGTATGCAGGTGGACTGAGGAAAGGTGGA ATAGATTACAAGAAATCAATATATTGTGGCAGGAATTATTGGAAGAACAGTGCTTGTTGAAAGCCTGG TTAACTGAAAAAGAAGAGGCTTTAAATAAAGTCCAGACATCCAACTTCAAAGACCAAAAGGAACTAAG TGTGAGTGTAAGAAGGCTGGCTATTTTGAAGGAAGACATGGAAATGAAGAGGCAAACATTGGATCAGC TGAGTGAGATAGGTCAGGATGTGGGACAATTACTTGATAATTCCAAGGCTTCTAAGAAGATCAACTCA GACAGTGAGGAACTGACTCAAAGGTGGGATTCTTTGGTTCAGAGACTAGAAGATTCCTCCAACCAGGT GACTCAGGCTGTGGCAAAGCTGGGGATGTCTCAGATTCCCCAGAAGGACCTTTTGGAGACAGTTAGGG TAAGGGAACAAGCCATTACAAAAAAATCTAAGCAGGAACTGCCACCTCCTCCTCCCCCTAAGAAGAGG CAGATCCATGTGGATTTGGAGAAACTCAGGGACCTGCAGGGAGCCATGGATGACCTGGATGCTGACAT GAAGGAGGCAGAGTCTGTGAGGAATGGTTGGAAGCCAGTGGGGGACTTACTCATAGACAGTCTGCAGG ATCACATTGAGAAAATCATGGCATTTAGGGAGGAAATTGCTCCCATCAACTTTAAAGTTAAAACAGTC AATGATTTATCCAGTCAGCTGTCCCCTCTTGACCTGCATCCCTCTCTAAAGATGTCTAGGCAGCTAGA TGACCTTAATATGAGGTGGAAACTTTTACAGGTTTCTGTGGATGATAGACTTAAACAGCTTCAGGAAG CCCACAGGGATTTTGGGCCCTCTTCCCAGCATTTTCTCTCTACCTCTGTCCAGCTGCCTTGGCAAAGA TCCATTTCACATAATAAAGTGCCCTATTACATCAACCATCAAACACAGACCACCTGTTGGGACCATCC 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 TATAAAAAAGAATGTGAGGAAGAGGCCATTAATATACAGTCCACAGCACCAGAGGAGGAGCATGAGAG TCCCAGGGCTGAAACTCCCAGCACTGTCACTGAGGTTGATATGGATCTGGACAGCTATCAGATTGCAT TGGAGGAAGTGCTGACCTGGTTGCTTTCTGCTGAGGACACTTTCCAGGAGCAGGATGATATTTCTGAT GATGTGGAGGAAGTCAAAGACCAGTTTGCTACCCATGAGGCATTTATGATGGAACTGACTGCACACCA GTCTTCTGTTGGGTCAGTGCTGCAGGCAGGTAACCAACTGATAACTCAAGGAACTCTGTCTGATGAAG AAGAATTTGAGATTCAGGAACAGATGACACTGCTGAATGCCAGATGGGAGGCTCTTAGGGTGGAGAGC ATGGACAGGCAGTCCAGGCTGCATGATGTGCTGATGGAACTGCAGAAGAAGCAACTGCAGCAGCTCTC TGCCTGGTTAACACTCACAGAGGAGAGGATTCAGAAGATGGAAACTTGCCCCCTGGATGATGATGTAA 71Attorney Docket No: 046192-000119WOPT AATCTCTACAAAAGCTGCTAGAAGAACATAAAAGTTTGCAAAGTGATCTTGAGGCTGAACAGGTGAAA GTAAATTCACTAACTCACATGGTGGTCATAGTTGATGAGAACTCAGGTGAGAGTGCCACAGCTATCCT AGAAGACCAGTTACAGAAACTGGGTGAGAGATGGACTGCAGTCTGCAGGTGGACAGAAGAAAGGTGGA ATAGGTTACAAGAAATCAATATATTGTGGCAGGAATTATTGGAAGAACAGTGCTTGTTGAAAGCATGG TTAACTGAAAAAGAAGAGGCTTTAAATAAAGTCCAGACAAGCAACTTCAAAGACCAAAAGGAACTAAG TGTCAGTGTTAGGAGGCTGGCTATTTTGAAGGAAGACATGGAAATGAAGAGACAAACATTGGATCAGC TGAGTGAGATAGGCCAGGATGTGGGACAATTACTTGATAATTCCAAGGCCTCTAAGAAGATCAACTCA GATTCAGAGGAACTGACTCAAAGGTGGGATTCCTTGGTTCAGAGACTAGAAGATTCCTCCAACCAGGT GACTCAGGCAGTAGCAAAGCTGGGGATGTCTCAGATTCCCCAGAAGGACCTTTTGGAGACTGTGAGAG TAAGGGAGCAAGCCATTACAAAAAAATCTAAGCAGGAACTGCCTCCTCCTCCTCCTCCTAAGAAGAGG CAGATCCATGTGGATTTGGAGAAACTCAGGGACCTGCAGGGAGCCATGGATGACCTGGATGCAGACAT GAAGGAGGCAGAGTCTGTGAGGAATGGCTGGAAGCCAGTGGGAGACTTACTCATTGACAGCCTGCAGG ATCACATAGAAAAAATCATGGCATTTAGAGAGGAAATAGCTCCCATCAACTTTAAAGTTAAAACAGTC AATGATTTATCCAGTCAGCTGAGCCCACTTGACCTGCATCCCTCTCTAAAGATGTCTAGACAGCTAGA TGATCTTAATATGAGGTGGAAACTTTTACAGGTTTCTGTGGATGATAGGCTTAAACAGCTTCAGGAAG CCCACAGGGATTTTGGACCATCCTCCCAGCATTTTCTCTCTACCTCTGTCCAGCTGCCCTGGCAAAGA TCCATTTCACATAATAAAGTGCCCTATTACATCAACCATCAAACACAGACCACCTGTTGGGACCATCC TAAAATGACTGAGCTCTTTCAATCCCTTGCTGATCTGAATAATGTGAGGTTTTCTGCCTACAGAACAG CCATCAAAATCAGAAGGCTACAAAAAGCACTATGTTTGGATCTCCTGGAGTTGAGTACAACAAATGAA ATTTTCAAACAGCACAAGTTGAACCAAAATGACCAGCTCCTCTCTGTGCCTGATGTGATCAACTGTCT GACAACAACTTATGATGGACTTGAGCAAATGCATAAGGACCTGGTCAATGTCCCTCTCTGTGTTGACA TGTGTCTCAATTGGTTGCTCAATGTGTATGACACAGGTAGAACAGGAAAAATTAGGGTGCAGAGTCTG AAGATTGGATTAATGTCTCTCTCCAAAGGTCTCTTGGAAGAAAAATACAGATATCTCTTTAAGGAAGT TGCTGGCCCAACAGAAATGTGTGACCAGAGGCAGCTGGGCCTGTTACTTCATGATGCTATCCAGATCC CAAGACAGCTAGGTGAAGTAGCTGCATTTGGTGGCAGTAATATAGAGCCTAGTGTGAGGAGCTGCTTC CAACAGAATAACAATAAACCAGAGATATCTGTGAAAGAGTTTATAGATTGGATGCATTTGGAACCACA GTCCATGGTTTGGCTCCCTGTTTTACATAGGGTGGCAGCTGCAGAGACTGCTAAACATCAGGCCAAAT GCAACATCTGTAAAGAATGTCCAATAGTGGGCTTCAGGTATAGGTCCCTTAAGCATTTTAACTATGAT GTTTGCCAGAGTTGTTTCTTTTCAGGCAGGACTGCCAAAGGTCACAAATTACATTACCCAATGGTGGA ATATTGTATACCTACAACATCTGGGGAAGATGTTAGAGACTTCACAAAGGTACTTAAGAACAAGTTCA GGAGCAAGAAGTACTTTGCAAAACACCCTAGGCTTGGTTACCTGCCTGTCCAGACAGTTCTTGAAGGT GACAACTTAGAGACTCAGGCAATGTGA

[0184] G9 (SEQ ID NO: 106)ATGGCTAAGTATGGGGAGCATGAGGCCAGTCCAGACAATGGACAGAATGAGTTCAGTGACATCATTAA GTCTAGGTCAGATGAGCACAATGATGTCCAGAAGAAAACCTTTACTAAATGGATAAATGCCAGATTTA GCAAGAGTGGGAAACCACCCATCAATGACATGTTCACTGACCTCAAAGATGGCAGGAAGCTATTGGAT CTTCTAGAGGGCCTCACTGGAACATCACTGCCAAAGGAAAGGGGTTCCACCAGGGTACATGCCTTAAA TAATGTCAACAGGGTGCTGCAGGTTTTACATCAGAACAATGTGGAATTAGTGAATATAGGAGGAACTG ACATAGTGGATGGCAATCACAAACTGACTTTGGGGTTACTTTGGAGCATCATTTTGCACTGGCAGGTG AAAGATGTGATGAAGGATGTGATGTCAGACCTGCAGCAGACCAACTCAGAAAAGATCCTGCTCAGCTG GGTGAGGCAGACAACCAGGCCCTACTCCCAAGTCAATGTCCTCAACTTCACCACCAGCTGGACAGATG GCCTGGCATTTAATGCTGTCCTCCACAGGCATAAACCAGACCTCTTCAGCTGGGATAAAGTTGTCAAA ATGTCACCAATAGAGAGGCTTGAACATGCTTTCAGCAAGGCTCAAACATATTTGGGAATAGAAAAGCT GCTGGATCCTGAAGATGTGGCTGTCCAGCTTCCTGACAAGAAATCAATAATTATGTATTTAACAAGCT TGTTTGAGGTGCTACCACAGCAAGTCACCATAGATGCAATCAGAGAGGTAGAGACCCTCCCAAGGAAA TATAAAAAAGAATGTGAAGAAGAGGCTATTAATATACAGTCCACTGCCCCAGAGGAGGAGCATGAGAG TCCTAGGGCAGAGACCCCAAGCACTGTCACTGAGGTTGATATGGATCTGGATAGCTATCAGATAGCAT TGGAGGAAGTGCTGACCTGGTTGCTTTCAGCTGAGGACACTTTCCAGGAGCAGGATGATATTTCTGAT GATGTGGAGGAAGTCAAAGACCAGTTTGCCACCCATGAGGCATTTATGATGGAACTGACTGCTCACCA GTCCAGTGTGGGCTCTGTTCTGCAGGCAGGGAACCAACTGATAACTCAAGGAACACTGTCTGATGAGG AAGAATTTGAGATTCAGGAACAGATGACTCTGCTGAATGCCAGATGGGAGGCCCTTAGGGTAGAGAGC ATGGACAGGCAGTCCAGACTGCATGATGTGCTGATGGAACTGCAGAAGAAGCAACTGCAGCAGCTCTC 72Attorney Docket No: 046192-000119WOPT TGCTTGGTTAACACTCACAGAGGAGAGGATTCAGAAGATGGAAACTTGCCCCCTGGATGATGATGTAA AATCTCTACAAAAGCTGCTAGAAGAACATAAAAGTTTGCAAAGTGACCTTGAGGCAGAGCAGGTGAAA GTAAATTCACTAACTCACATGGTGGTCATTGTTGATGAAAACTCAGGGGAGTCAGCTACAGCTATCCT AGAAGACCAGTTACAGAAATTGGGTGAGAGGTGGACAGCTGTATGCAGGTGGACTGAGGAAAGGTGGA ATAGGTTACAAGAAATCAATATATTGTGGCAGGAATTATTGGAAGAACAGTGCTTGTTGAAAGCTTGG TTAACAGAGAAAGAAGAGGCTTTAAATAAAGTCCAGACATCCAACTTCAAAGACCAAAAGGAACTAAG TGTATCTGTGAGGAGGCTGGCTATTTTGAAGGAAGACATGGAAATGAAGAGACAAACATTGGATCAGC TGTCAGAGATAGGGCAGGATGTGGGACAATTACTTGATAATTCCAAGGCATCTAAGAAGATCAACTCA GACTCAGAGGAACTGACTCAAAGGTGGGATTCCTTGGTTCAGAGACTAGAAGATTCCTCCAACCAGGT GACTCAGGCTGTAGCAAAGCTGGGGATGTCTCAGATTCCACAGAAGGACCTTTTGGAGACTGTCAGGG TAAGGGAGCAAGCCATTACAAAAAAATCTAAGCAGGAACTGCCCCCTCCTCCTCCCCCCAAGAAGAGG CAGATCCATGTGGATTTGGAGAAACTCAGGGACCTGCAGGGTGCCATGGATGACCTGGATGCTGACAT GAAGGAGGCTGAGTCTGTGAGGAATGGGTGGAAGCCAGTTGGGGACTTACTCATAGATAGCCTGCAGG ATCACATAGAGAAAATCATGGCATTTAGAGAAGAAATAGCCCCTATCAACTTTAAAGTTAAAACAGTG AATGACTTATCCAGTCAGCTGTCCCCTCTTGACCTGCATCCCTCTCTAAAGATGTCTAGGCAGCTAGA TGACCTTAATATGAGGTGGAAACTTTTACAGGTTTCTGTGGATGACAGGCTTAAACAGCTTCAGGAAG CCCACAGGGATTTTGGACCATCATCACAGCATTTTCTCTCTACCAGTGTGCAGCTGCCATGGCAAAGA TCCATTTCACATAATAAAGTGCCCTATTACATCAACCATCAAACACAGACCACCTGTTGGGACCATCC TAAAATGACTGAACTCTTTCAATCCCTTGCTGACCTGAATAATGTAAGGTTTTCTGCCTACAGGACAG CCATCAAAATCAGGAGACTACAAAAAGCACTATGTTTGGATCTCCTGGAGTTGAGTACAACAAATGAG ATTTTCAAACAGCACAAGTTGAACCAAAATGATCAGCTCCTCAGTGTCCCTGATGTGATCAACTGTCT GACAACAACTTATGATGGGCTTGAGCAAATGCATAAGGACCTGGTCAATGTGCCTCTCTGTGTGGATA TGTGTCTCAATTGGTTGCTCAATGTATATGATACTGGGAGGACTGGAAAAATTAGGGTGCAGAGTCTG AAGATAGGCTTAATGTCTCTCTCCAAAGGTCTCTTGGAAGAAAAATACAGATATCTCTTTAAGGAAGT GGCAGGGCCAACTGAAATGTGTGATCAGAGGCAGCTGGGCCTGTTACTTCATGATGCCATCCAGATCC CTAGGCAGCTAGGTGAAGTAGCTGCTTTTGGAGGCAGTAATATAGAGCCAAGTGTCAGGAGCTGCTTC CAACAGAATAACAATAAACCTGAAATAAGTGTGAAAGAGTTTATAGACTGGATGCATTTGGAACCACA GTCCATGGTTTGGCTCCCTGTTTTACATAGGGTGGCAGCTGCAGAGACTGCCAAACATCAGGCCAAAT GCAACATCTGTAAAGAATGTCCTATAGTGGGGTTCAGGTATAGATCCCTTAAGCATTTTAACTATGAT GTCTGCCAGAGTTGTTTCTTTTCTGGGAGGACTGCCAAAGGTCACAAATTACATTACCCAATGGTGGA ATATTGTATACCTACAACATCTGGGGAAGATGTTAGGGATTTCACTAAGGTACTTAAGAACAAGTTCA GGTCTAAGAAGTACTTTGCAAAACACCCTAGGCTTGGTTACCTGCCAGTGCAGACAGTCCTTGAAGGT GACAACTTAGAGACTCAGGCCATGTGA

[0185] G10 (SEQ ID NO: 107)ATGGCAAAGTATGGGGAGCATGAAGCAAGTCCAGACAATGGACAGAATGAATTCTCAGATATCATTAA GTCCAGGTCTGATGAACACAATGATGTACAGAAGAAAACCTTTACCAAATGGATAAATGCCAGGTTTA GCAAGAGTGGCAAACCACCCATCAATGATATGTTCACTGACCTCAAAGATGGAAGGAAGCTATTGGAT CTTCTGGAAGGCCTCACTGGAACATCACTGCCAAAGGAAAGGGGTTCCACCAGAGTACATGCCTTAAA TAATGTCAACAGGGTGCTGCAGGTTTTACATCAGAACAATGTTGAATTAGTGAATATAGGTGGCACTG ATATAGTTGATGGGAATCACAAACTGACCTTGGGGTTACTTTGGAGCATCATTTTGCACTGGCAGGTG AAAGATGTCATGAAGGATGTGATGTCTGACCTGCAGCAGACAAACAGTGAGAAGATCCTGCTCAGCTG GGTGAGGCAGACCACCAGACCCTACAGCCAAGTCAATGTCCTCAACTTCACCACCAGCTGGACAGATG GCCTGGCTTTTAATGCAGTGCTCCACAGGCATAAACCAGATCTCTTCAGCTGGGATAAAGTTGTCAAA ATGTCACCAATAGAAAGGCTTGAACATGCCTTCAGCAAGGCTCAAACCTATTTGGGAATAGAGAAGCT GTTAGACCCAGAAGATGTTGCAGTCCAGCTTCCTGACAAGAAATCTATAATTATGTATTTAACTTCCT TGTTTGAGGTGCTACCCCAGCAAGTCACCATAGATGCCATCAGGGAGGTAGAGACCCTCCCAAGGAAA TATAAAAAAGAATGTGAGGAAGAGGCCATTAATATACAGAGCACAGCTCCAGAGGAGGAGCATGAGAG TCCAAGGGCTGAGACCCCTAGCACAGTCACTGAGGTGGACATGGATCTGGACAGCTATCAGATTGCCT TGGAGGAAGTGCTGACCTGGTTGCTTTCAGCTGAGGACACTTTCCAGGAGCAGGATGACATTTCTGAT GATGTTGAAGAAGTCAAAGACCAGTTTGCCACCCATGAAGCCTTTATGATGGAACTGACTGCACACCA GTCCAGTGTAGGCTCTGTCCTGCAGGCTGGCAACCAACTGATAACCCAAGGAACCCTGTCTGATGAAG AAGAATTTGAGATTCAGGAACAGATGACTCTGCTGAATGCTAGATGGGAGGCACTTAGGGTGGAGAGT ATGGACAGGCAGTCCAGACTGCATGATGTTCTGATGGAACTGCAGAAGAAGCAACTGCAGCAGCTCTC 73Attorney Docket No: 046192-000119WOPT AGCATGGTTAACACTCACAGAGGAGAGGATTCAGAAGATGGAAACTTGCCCCCTGGATGATGATGTGA AATCTCTACAAAAGCTGCTAGAAGAACATAAAAGTTTGCAATCAGATCTTGAGGCTGAACAGGTGAAA GTAAATTCACTAACTCACATGGTGGTGATTGTGGATGAGAACTCAGGGGAGAGTGCTACAGCAATCCT AGAAGACCAGTTACAGAAACTGGGGGAGAGATGGACAGCAGTCTGCAGGTGGACAGAGGAAAGATGGA ATAGGTTACAAGAAATCAATATATTGTGGCAGGAATTATTGGAAGAACAGTGCTTGTTGAAAGCTTGG TTAACTGAAAAAGAAGAGGCTTTAAATAAAGTCCAGACAAGCAACTTCAAAGACCAAAAGGAACTATC AGTGTCAGTTAGAAGGCTGGCTATTTTGAAGGAAGACATGGAAATGAAGAGGCAAACATTGGATCAGC TGAGTGAGATAGGGCAGGATGTGGGGCAATTACTTGATAATTCCAAGGCATCTAAGAAGATCAACTCT GACTCAGAGGAACTGACTCAAAGGTGGGATTCTTTGGTTCAGAGACTAGAAGATTCCTCCAACCAGGT GACTCAGGCAGTTGCAAAGCTGGGGATGTCTCAGATTCCACAGAAGGACCTTTTGGAGACTGTGAGAG TAAGGGAGCAAGCCATTACAAAAAAATCTAAGCAGGAACTGCCACCTCCTCCTCCTCCTAAGAAGAGA CAGATCCATGTGGATTTGGAGAAACTCAGGGACCTGCAGGGAGCCATGGATGACCTGGATGCTGATAT GAAGGAGGCTGAGTCTGTCAGGAATGGCTGGAAGCCTGTGGGAGACTTACTCATAGATTCCCTGCAGG ATCACATAGAGAAAATCATGGCATTTAGGGAAGAAATTGCTCCTATCAACTTTAAAGTTAAAACAGTG AATGATTTATCCAGTCAGCTGTCTCCTCTTGACCTGCATCCCTCTCTAAAGATGTCTAGGCAGCTAGA TGACCTTAATATGAGATGGAAACTTTTACAGGTTTCTGTTGATGATAGGCTTAAACAGCTTCAGGAAG CCCACAGGGATTTTGGCCCTAGCTCCCAGCATTTTCTCTCTACTTCAGTCCAGCTGCCTTGGCAAAGA TCCATTTCACATAATAAAGTGCCTTATTACATCAACCATCAAACACAGACCACCTGTTGGGACCATCC TAAAATGACTGAGCTCTTTCAATCCCTTGCTGACCTGAATAATGTGAGATTTTCAGCCTACAGGACTG CAATCAAAATCAGGAGGCTACAAAAAGCACTATGTTTGGATCTCCTGGAGTTGAGTACAACAAATGAG ATTTTCAAACAGCACAAGTTGAACCAAAATGACCAGCTCCTCTCTGTCCCAGATGTGATCAACTGTCT GACAACAACTTATGATGGCCTTGAGCAAATGCATAAGGACCTGGTCAATGTCCCTCTCTGTGTGGATA TGTGTCTCAATTGGTTGCTCAATGTCTATGACACTGGTAGAACTGGAAAAATTAGAGTGCAGAGTCTG AAGATTGGGTTAATGTCTCTCTCCAAAGGTCTCTTGGAAGAAAAATACAGATATCTCTTTAAGGAAGT TGCAGGGCCAACAGAAATGTGTGACCAGAGGCAGCTGGGCCTGTTACTTCATGATGCTATCCAGATCC CTAGGCAGCTAGGTGAAGTAGCTGCCTTTGGAGGCAGTAATATAGAGCCTTCTGTGAGGAGCTGCTTC CAACAGAATAACAATAAACCTGAAATAAGTGTGAAAGAGTTTATAGACTGGATGCATTTGGAACCACA GTCCATGGTTTGGCTCCCTGTTTTACATAGGGTGGCAGCAGCTGAGACAGCAAAACATCAGGCCAAAT GCAACATCTGTAAAGAATGTCCTATTGTGGGGTTCAGGTATAGGAGTCTTAAGCATTTTAACTATGAT GTCTGCCAGAGTTGTTTCTTTTCAGGCAGGACTGCCAAAGGTCACAAATTACATTACCCAATGGTGGA ATATTGTATACCTACAACAAGTGGGGAAGATGTCAGGGACTTCACCAAGGTACTTAAGAACAAGTTCA GGTCCAAGAAGTACTTTGCCAAACACCCTAGACTTGGTTACCTGCCTGTCCAGACAGTCCTTGAAGGT GACAACTTAGAGACTCAGGCAATGTGA

[0186] G11 (SEQ ID NO: 108)ATGGCCAAGTATGGGGAACATGAAGCCAGTCCAGACAATGGCCAGAATGAATTCAGTGATATCATTAA GTCCAGATCAGATGAGCACAATGATGTGCAGAAGAAAACCTTTACCAAATGGATAAATGCTAGGTTTT CAAAGTCAGGTAAACCACCCATCAATGACATGTTCACTGACCTCAAAGATGGAAGGAAGCTACTTGAT CTTCTAGAAGGCCTCACAGGAACATCACTGCCTAAGGAAAGAGGTTCCACAAGGGTACATGCCTTAAA TAATGTCAACAGAGTGCTGCAGGTTTTACATCAGAACAATGTGGAATTAGTTAATATTGGGGGCACTG ACATAGTGGATGGCAATCACAAACTGACTTTGGGGTTACTTTGGTCAATCATTTTGCACTGGCAGGTG AAAGATGTCATGAAGGATGTCATGTCAGACCTGCAGCAGACTAACTCTGAGAAGATCCTGCTCAGCTG GGTGAGGCAGACCACCAGGCCATACTCCCAAGTCAATGTGCTCAACTTCACCACCAGCTGGACAGATG GACTGGCCTTTAATGCTGTCCTCCACAGGCATAAACCTGATCTCTTCAGCTGGGATAAAGTTGTCAAA ATGTCACCAATTGAGAGACTTGAACATGCCTTCAGCAAGGCCCAAACATATTTGGGAATAGAAAAGCT GTTAGATCCAGAAGATGTTGCTGTTCAGCTTCCAGACAAGAAATCCATAATTATGTATTTAACATCTT TGTTTGAGGTGCTACCTCAGCAAGTCACCATAGATGCTATCAGGGAGGTAGAGACCCTCCCAAGGAAA TATAAAAAAGAATGTGAGGAAGAGGCAATTAATATACAGTCTACTGCTCCTGAGGAGGAGCATGAGAG TCCCAGAGCAGAAACTCCCAGCACAGTCACAGAGGTTGATATGGATCTGGACAGCTATCAGATTGCTT TGGAGGAAGTGCTGACCTGGTTGCTTAGTGCAGAAGACACCTTCCAGGAGCAGGATGATATTTCAGAT GATGTGGAAGAAGTCAAAGACCAGTTTGCCACCCATGAGGCTTTTATGATGGAACTGACTGCACACCA GAGCTCTGTGGGCAGTGTCCTGCAGGCTGGCAACCAACTGATAACACAAGGAACTCTGTCAGATGAGG AAGAATTTGAGATTCAGGAACAGATGACACTGCTGAATGCTAGATGGGAGGCTCTTAGGGTGGAGAGT ATGGACAGGCAGTCCAGACTGCATGATGTGCTGATGGAACTGCAGAAGAAGCAACTGCAGCAGCTCTC 74Attorney Docket No: 046192-000119WOPT AGCCTGGTTAACACTCACAGAGGAGAGAATTCAGAAGATGGAAACCTGCCCACTGGATGATGATGTGA AATCTCTACAAAAGCTGCTAGAAGAACATAAAAGTTTGCAATCTGACCTTGAGGCTGAACAGGTGAAA GTAAATTCACTAACTCACATGGTGGTCATTGTAGATGAGAACAGTGGGGAGAGTGCCACAGCTATCCT AGAAGACCAGTTACAGAAACTTGGGGAGAGATGGACTGCAGTGTGCAGGTGGACTGAGGAAAGGTGGA ATAGATTACAAGAAATCAATATATTGTGGCAGGAATTATTGGAAGAACAGTGCTTGTTGAAAGCTTGG TTAACTGAGAAAGAAGAGGCCTTAAATAAAGTCCAGACTAGCAACTTCAAAGACCAAAAGGAACTAAG TGTGAGTGTTAGGAGGCTGGCTATTTTGAAGGAAGACATGGAAATGAAGAGACAAACTTTGGATCAGC TGAGTGAGATTGGCCAGGATGTAGGGCAATTACTTGACAATTCCAAGGCCTCTAAGAAGATCAACAGT GACTCAGAGGAACTGACTCAAAGATGGGATTCTCTAGTTCAGAGACTGGAAGATTCCTCCAACCAGGT GACTCAGGCTGTGGCTAAGCTGGGGATGAGCCAGATTCCTCAGAAGGACCTTTTGGAAACTGTCAGGG TAAGAGAACAAGCCATTACAAAAAAATCTAAGCAGGAACTGCCTCCTCCTCCCCCCCCAAAGAAGAGG CAGATCCATGTGGATTTGGAAAAACTCAGGGACCTGCAGGGGGCTATGGATGACCTGGATGCTGACAT GAAGGAGGCTGAGTCTGTGAGAAATGGCTGGAAGCCTGTGGGAGACTTACTCATAGATAGCCTGCAGG ATCACATTGAAAAAATCATGGCCTTTAGGGAAGAAATTGCACCTATCAACTTTAAAGTTAAAACTGTT AATGATTTATCCTCACAGCTGAGCCCACTTGACCTGCATCCAAGCCTAAAGATGTCTAGGCAGCTAGA TGATCTTAATATGAGATGGAAACTTTTACAGGTTTCTGTGGATGATAGACTTAAACAGCTTCAGGAAG CCCACAGAGATTTTGGCCCATCCTCTCAGCATTTTCTCTCTACAAGTGTCCAGCTGCCCTGGCAAAGA TCCATTTCACATAATAAAGTGCCCTATTACATCAACCATCAAACACAGACTACATGTTGGGACCATCC TAAAATGACAGAGCTCTTTCAATCTCTTGCTGACCTGAATAATGTCAGGTTTTCAGCTTACAGAACAG CTATCAAAATCAGGAGGCTACAAAAAGCACTATGTTTGGACCTCTTAGAGTTGAGTACTACAAATGAG ATTTTCAAACAGCACAAGTTGAACCAAAATGACCAGCTCCTCTCTGTCCCTGATGTAATCAACTGTCT GACCACAACATATGATGGCCTTGAGCAAATGCATAAGGACCTGGTCAATGTGCCACTCTGTGTAGATA TGTGTCTCAATTGGTTGCTCAATGTGTATGACACAGGTAGGACTGGAAAAATTAGGGTGCAGAGTCTG AAGATTGGTTTAATGTCTCTCTCTAAAGGTCTCTTGGAAGAAAAATACAGATATCTCTTTAAGGAAGT TGCAGGACCCACAGAAATGTGTGACCAGAGGCAGCTGGGCCTGTTACTTCATGATGCTATCCAGATCC CAAGGCAGCTGGGGGAAGTAGCAGCATTTGGAGGGAGCAATATAGAGCCAAGTGTTAGGAGCTGCTTC CAACAGAATAACAATAAACCAGAAATATCAGTGAAAGAGTTTATAGATTGGATGCATTTGGAGCCCCA GTCCATGGTTTGGCTCCCAGTGTTACATAGGGTAGCTGCTGCAGAGACTGCCAAACATCAGGCCAAAT GCAACATCTGTAAAGAATGTCCAATTGTGGGCTTCAGGTATAGATCTCTTAAGCATTTTAACTATGAT GTCTGCCAGAGTTGTTTCTTTAGTGGTAGAACTGCAAAAGGTCACAAATTACATTACCCAATGGTGGA GTATTGTATACCTACAACATCAGGTGAAGATGTCAGAGATTTCACAAAGGTACTTAAGAACAAGTTCA GGTCAAAGAAGTACTTTGCTAAACACCCAAGACTGGGTTACCTGCCTGTACAGACTGTTCTTGAGGGT GACAACTTAGAAACTCAGGCTATGTGA

[0187] G12 (SEQ ID NO: 109)ATGGCTAAGTATGGGGAACATGAGGCCAGTCCAGACAATGGGCAGAATGAATTCTCTGATATCATTAA GTCCAGATCTGATGAACACAATGATGTGCAGAAGAAAACCTTTACCAAATGGATAAATGCTAGATTTT CAAAGAGTGGGAAACCACCCATCAATGACATGTTCACTGACCTCAAAGATGGGAGAAAGCTACTAGAT CTTCTAGAAGGCCTCACTGGAACATCACTGCCCAAGGAAAGGGGTTCCACAAGGGTACATGCCTTAAA TAATGTCAACAGAGTGCTGCAGGTTTTACATCAGAACAATGTGGAACTGGTGAATATAGGTGGCACTG ACATTGTGGATGGCAATCACAAACTGACTTTGGGGTTACTTTGGTCTATCATTTTGCACTGGCAGGTG AAAGATGTCATGAAGGATGTGATGTCAGACCTGCAGCAGACAAACTCAGAAAAGATCCTGCTCAGCTG GGTGAGACAGACCACTAGGCCTTACAGTCAAGTCAATGTCCTCAACTTCACCACCAGCTGGACAGATG GCCTGGCCTTTAATGCTGTCCTCCACAGACATAAACCTGATCTCTTCAGCTGGGATAAAGTTGTCAAA ATGTCACCAATTGAGAGGCTTGAACATGCTTTCAGCAAGGCCCAAACTTATTTGGGAATTGAAAAGCT GTTAGATCCTGAAGATGTGGCAGTGCAGCTTCCAGACAAGAAATCCATAATTATGTATTTAACATCTT TGTTTGAGGTGCTACCTCAGCAAGTCACCATTGATGCCATCAGAGAGGTAGAGACTCTCCCAAGGAAA TATAAAAAAGAATGTGAGGAAGAGGCAATTAATATACAGTCCACAGCCCCTGAGGAGGAGCATGAGAG TCCCAGAGCTGAGACTCCCAGCACAGTCACAGAGGTGGACATGGATCTGGACAGTTATCAGATTGCTC TGGAGGAAGTGCTGACCTGGTTGCTTTCAGCTGAAGACACTTTCCAGGAGCAGGATGACATTTCTGAT GATGTGGAGGAAGTCAAAGACCAGTTTGCAACTCATGAGGCTTTTATGATGGAACTGACTGCTCACCA GAGCAGTGTGGGCAGTGTGCTGCAGGCAGGCAACCAACTGATAACCCAAGGAACTCTGAGTGATGAAG AAGAATTTGAGATTCAGGAACAGATGACTCTGCTGAATGCCAGATGGGAGGCTCTTAGGGTGGAGAGT ATGGACAGGCAGTCAAGACTGCATGATGTGCTGATGGAACTGCAGAAGAAGCAACTGCAGCAGCTCTC 75Attorney Docket No: 046192-000119WOPT AGCCTGGTTAACACTCACTGAGGAGAGGATTCAGAAGATGGAAACCTGCCCTCTGGATGATGATGTCA AATCTCTACAAAAGCTGCTAGAAGAACATAAAAGTTTGCAATCTGATCTTGAGGCTGAACAGGTGAAA GTAAATTCACTAACTCACATGGTGGTGATTGTTGATGAAAACAGTGGAGAGAGTGCAACAGCTATCCT AGAAGACCAGTTACAGAAACTTGGTGAGAGGTGGACTGCAGTCTGCAGATGGACAGAAGAAAGATGGA ATAGGTTACAAGAAATCAATATATTGTGGCAGGAATTATTGGAAGAACAGTGCTTGTTGAAAGCTTGG TTAACTGAGAAAGAAGAGGCCTTAAATAAAGTCCAGACAAGCAACTTCAAAGACCAAAAGGAACTAAG TGTGTCTGTTAGGAGGCTGGCTATTTTGAAGGAAGACATGGAAATGAAGAGACAAACCTTGGATCAGC TGAGTGAGATTGGGCAGGATGTGGGTCAATTACTTGATAATTCCAAGGCCTCTAAGAAGATCAACAGT GACTCTGAAGAACTGACTCAAAGATGGGATTCTCTTGTTCAGAGATTGGAAGATTCCTCCAACCAGGT GACTCAGGCAGTGGCCAAGTTAGGGATGTCTCAGATTCCTCAGAAGGACCTTTTGGAGACAGTTAGAG TAAGAGAACAAGCCATTACTAAAAAATCCAAGCAGGAACTGCCTCCTCCTCCTCCCCCAAAGAAGAGA CAGATCCATGTGGATTTGGAAAAACTCAGGGACCTGCAGGGAGCCATGGATGATCTGGATGCTGACAT GAAGGAGGCTGAAAGTGTGAGAAATGGATGGAAGCCAGTGGGAGACTTACTCATTGACTCACTGCAGG ATCACATTGAGAAAATCATGGCATTTAGGGAAGAAATTGCACCCATCAACTTTAAAGTTAAAACTGTG AATGATTTATCTAGCCAGCTGAGTCCCCTTGACCTGCATCCAAGCCTAAAGATGTCTAGACAGCTAGA TGATCTTAATATGAGGTGGAAACTTTTACAGGTTTCTGTTGATGACAGACTTAAACAGCTTCAGGAAG CCCACAGAGATTTTGGGCCATCCTCTCAGCATTTTCTCTCTACTTCTGTGCAGCTGCCCTGGCAAAGA TCCATTTCACATAATAAAGTGCCATATTACATCAACCATCAAACACAGACCACATGTTGGGACCATCC TAAAATGACTGAACTCTTTCAAAGCCTTGCAGACCTGAATAATGTAAGATTTTCAGCCTACAGGACAG CTATCAAAATCAGGAGACTACAAAAAGCACTATGTTTGGACCTCTTAGAGTTGAGTACTACAAATGAA ATTTTCAAACAGCACAAGTTGAACCAAAATGACCAGCTCCTCAGTGTGCCAGATGTAATCAACTGTCT GACAACAACCTATGATGGACTTGAGCAAATGCATAAGGACCTGGTCAATGTGCCACTCTGTGTGGATA TGTGTCTCAATTGGTTGCTCAATGTGTATGACACAGGTAGGACAGGAAAAATTAGGGTGCAGAGTCTG AAGATAGGATTAATGTCTCTCAGCAAAGGTCTCTTGGAAGAAAAATACAGGTATCTCTTTAAGGAAGT GGCAGGTCCAACAGAAATGTGTGATCAGAGGCAGCTGGGCCTGTTACTTCATGATGCCATCCAGATCC CTAGGCAGCTGGGTGAGGTAGCAGCCTTTGGTGGCTCAAATATTGAGCCCTCTGTTAGAAGCTGCTTC CAACAGAATAACAATAAACCTGAAATAAGTGTGAAAGAGTTTATAGATTGGATGCATTTGGAGCCCCA GTCCATGGTTTGGCTCCCAGTTTTACATAGAGTTGCAGCAGCTGAGACTGCCAAACATCAGGCCAAAT GCAACATCTGTAAAGAATGTCCAATTGTAGGCTTCAGGTATAGGTCTCTTAAGCATTTTAACTATGAT GTGTGCCAGAGTTGTTTCTTTTCTGGCAGAACAGCTAAAGGTCACAAATTACATTACCCAATGGTGGA ATATTGTATACCTACAACATCTGGGGAAGATGTTAGAGACTTCACAAAGGTACTTAAGAACAAGTTCA GGAGTAAGAAGTACTTTGCCAAACACCCCAGATTGGGTTACCTGCCAGTCCAGACAGTTCTGGAAGGT GACAACTTAGAGACTCAGGCCATGTGA

[0188] G13 (SEQ ID NO: 110)ATGGCTAAGTATGGAGAACATGAAGCTAGTCCTGACAATGGGCAGAATGAGTTCAGTGACATCATTAA GTCCAGATCTGATGAGCACAATGATGTCCAGAAGAAAACCTTTACCAAATGGATAAATGCCAGGTTTT CAAAGAGTGGGAAACCACCTATCAATGATATGTTCACAGACCTCAAAGATGGAAGGAAGCTACTGGAT CTTCTAGAAGGCCTCACTGGGACATCACTGCCTAAGGAAAGGGGTTCCACAAGGGTACATGCTTTAAA TAATGTCAACAGGGTGCTGCAGGTTTTACATCAGAACAATGTGGAACTGGTGAATATTGGGGGTACAG ACATTGTGGATGGCAATCACAAACTGACTTTGGGGTTACTTTGGTCAATCATTTTGCACTGGCAGGTG AAAGATGTGATGAAGGATGTTATGTCTGACCTGCAGCAGACTAACAGTGAAAAGATCCTGCTCAGCTG GGTGAGGCAGACCACTAGGCCCTACTCCCAAGTCAATGTTCTCAACTTCACCACCTCTTGGACAGATG GCTTAGCCTTTAATGCTGTGCTCCACAGGCATAAACCAGACCTCTTCAGCTGGGATAAAGTTGTCAAA ATGTCACCAATTGAGAGACTTGAACATGCCTTCAGCAAGGCTCAAACCTATTTGGGAATTGAAAAGCT GTTAGATCCAGAAGATGTGGCTGTTCAGCTTCCAGACAAGAAATCCATAATTATGTATTTAACATCTT TGTTTGAAGTGCTACCTCAGCAAGTCACTATAGATGCTATCAGGGAGGTAGAGACACTCCCTAGGAAA TATAAAAAAGAATGTGAAGAAGAGGCAATTAATATACAGAGTACAGCCCCAGAAGAGGAGCATGAGAG TCCCAGGGCTGAGACTCCCAGCACTGTCACAGAGGTAGACATGGATCTGGACTCTTATCAGATTGCAC TGGAGGAAGTGCTGACCTGGTTGCTTTCTGCAGAGGACACTTTCCAGGAGCAGGATGACATTTCTGAT GATGTTGAGGAAGTCAAAGACCAGTTTGCTACCCATGAGGCTTTTATGATGGAACTGACTGCTCACCA GAGCAGTGTGGGCAGTGTGCTGCAGGCAGGCAACCAACTGATAACCCAAGGAACTCTGTCAGATGAAG AAGAATTTGAGATTCAGGAACAGATGACTCTGCTGAATGCTAGATGGGAGGCTCTTAGGGTGGAGAGT ATGGACAGACAGAGTAGGCTGCATGATGTCCTGATGGAACTGCAGAAGAAGCAACTGCAGCAGCTCAG 76Attorney Docket No: 046192-000119WOPT TGCTTGGTTAACACTCACAGAGGAGAGAATTCAGAAGATGGAAACCTGCCCCCTGGATGATGATGTCA AATCTCTACAAAAGCTGCTAGAAGAACATAAAAGTTTGCAATCAGATCTTGAGGCTGAGCAGGTGAAA GTAAATTCACTAACTCACATGGTGGTCATTGTTGATGAAAACAGTGGTGAGAGTGCTACAGCCATCCT AGAAGACCAGTTACAGAAACTTGGAGAGAGGTGGACTGCAGTATGCAGATGGACAGAAGAAAGATGGA ATAGGTTACAAGAAATCAATATATTGTGGCAGGAATTATTGGAAGAACAGTGCTTGTTGAAAGCTTGG TTAACAGAAAAAGAAGAGGCCTTAAATAAAGTCCAGACCAGCAACTTCAAAGACCAAAAGGAACTAAG TGTGAGTGTGAGGAGGCTGGCTATTTTGAAGGAAGACATGGAAATGAAGAGGCAAACATTGGATCAGC TGAGTGAAATTGGCCAGGATGTGGGACAATTACTAGATAATTCCAAGGCCTCTAAGAAGATCAACTCT GACTCTGAGGAACTGACTCAAAGATGGGATTCTTTGGTTCAGAGACTTGAAGATTCCTCCAACCAGGT GACTCAGGCTGTTGCTAAGCTGGGGATGTCACAGATTCCTCAGAAGGACCTTTTGGAGACTGTAAGAG TAAGAGAACAAGCAATTACCAAAAAATCAAAGCAGGAACTGCCTCCTCCTCCTCCCCCAAAGAAGAGA CAGATCCATGTGGATTTAGAGAAACTCAGAGACCTGCAGGGGGCTATGGATGACCTGGATGCAGATAT GAAGGAGGCTGAGAGTGTGAGGAATGGCTGGAAGCCTGTGGGAGACTTACTCATTGATAGCCTGCAGG ATCACATTGAGAAAATCATGGCCTTTAGAGAAGAAATTGCCCCTATCAACTTTAAAGTTAAAACAGTC AATGACTTATCCAGCCAGCTGTCCCCACTTGACCTGCATCCATCCCTAAAGATGTCTAGACAGCTAGA TGACCTTAATATGAGGTGGAAACTTTTACAGGTTAGTGTGGATGATAGGCTTAAACAGCTTCAGGAAG CCCACAGAGATTTTGGACCATCCTCTCAGCATTTTCTCTCTACTAGTGTTCAGCTGCCATGGCAAAGA TCCATTTCACATAATAAAGTGCCATATTACATCAACCATCAAACACAGACAACCTGTTGGGACCATCC TAAAATGACAGAACTCTTTCAATCCCTTGCTGATCTGAATAATGTGAGGTTTTCAGCTTACAGAACTG CCATCAAAATCAGAAGACTACAAAAAGCACTATGTCTTGATCTCTTAGAGTTGAGTACCACAAATGAA ATTTTCAAACAGCACAAGTTGAACCAAAATGACCAGCTCCTCAGTGTTCCAGATGTCATCAACTGTCT GACCACAACATATGATGGCTTGGAGCAAATGCATAAGGACCTGGTCAATGTGCCCCTCTGTGTGGATA TGTGTCTCAATTGGTTGCTCAATGTCTATGACACTGGTAGGACAGGCAAAATTAGAGTGCAGAGTCTG AAGATTGGTTTAATGTCTCTCAGTAAAGGTCTCTTGGAAGAAAAATACAGATATCTCTTTAAGGAAGT GGCTGGGCCCACTGAAATGTGTGACCAGAGGCAGCTGGGCCTGTTACTTCATGATGCCATCCAGATCC CAAGGCAGCTGGGGGAAGTAGCAGCCTTTGGAGGCAGCAATATTGAACCTTCTGTTAGAAGCTGCTTC CAACAGAATAACAATAAACCAGAGATAAGTGTCAAAGAGTTTATTGACTGGATGCATCTGGAACCTCA GTCCATGGTTTGGCTCCCAGTGTTACATAGGGTGGCTGCTGCAGAAACTGCCAAACATCAGGCCAAAT GCAACATCTGTAAAGAATGTCCAATTGTGGGTTTCAGGTATAGGTCCCTTAAGCATTTTAACTATGAT GTCTGCCAGAGTTGTTTCTTTAGTGGGAGAACAGCAAAAGGTCACAAATTACATTACCCAATGGTGGA GTATTGTATACCTACAACATCTGGGGAGGATGTAAGAGACTTCACAAAGGTACTTAAGAACAAGTTCA GGTCAAAGAAGTACTTTGCTAAACACCCTAGACTGGGTTACCTGCCTGTCCAGACTGTGCTTGAGGGT GACAACTTAGAGACTCAGGCCATGTGA

[0189] G14 (SEQ ID NO: 111)ATGGCTAAGTATGGAGAACATGAGGCCAGTCCAGACAATGGGCAGAATGAGTTCAGTGACATCATTAA GTCCAGAAGTGATGAACACAATGATGTACAGAAGAAAACCTTTACCAAATGGATAAATGCTAGATTTT CAAAGTCTGGGAAACCACCTATCAATGATATGTTCACAGACCTCAAAGATGGCAGAAAGCTATTGGAC CTTCTAGAAGGCCTCACTGGCACATCACTGCCCAAGGAAAGAGGTTCCACAAGGGTACATGCATTAAA TAATGTTAACAGGGTGCTGCAGGTTTTACATCAGAACAATGTGGAACTGGTGAATATAGGTGGAACTG ATATTGTGGATGGCAATCACAAACTGACTTTGGGGTTACTTTGGAGTATCATTTTGCACTGGCAGGTG AAAGATGTTATGAAGGATGTGATGTCTGACCTGCAGCAGACCAACTCAGAGAAGATCCTGCTCAGCTG GGTGAGGCAGACCACTAGGCCATACTCCCAAGTCAATGTGCTCAACTTCACCACCTCCTGGACAGATG GCCTTGCCTTTAATGCTGTCCTCCACAGACATAAACCTGATCTCTTCAGCTGGGATAAAGTTGTCAAA ATGTCACCAATTGAGAGGCTTGAACATGCCTTCAGCAAGGCCCAAACTTATTTGGGAATTGAAAAGCT GTTAGATCCTGAAGATGTGGCTGTGCAGCTTCCAGACAAGAAATCCATAATTATGTATTTAACATCTT TGTTTGAGGTGCTACCTCAGCAAGTCACAATTGATGCTATCAGAGAGGTAGAGACCCTCCCCAGGAAA TATAAAAAAGAATGTGAGGAAGAGGCAATTAATATACAGAGCACAGCTCCAGAGGAGGAGCATGAGAG TCCCAGGGCAGAGACTCCCAGCACTGTTACAGAGGTTGACATGGATCTGGACTCATATCAGATTGCCC TGGAGGAAGTGCTGACCTGGTTGCTTAGTGCAGAGGACACTTTCCAGGAGCAGGATGACATTAGTGAT GATGTGGAAGAAGTCAAAGACCAGTTTGCCACCCATGAGGCTTTTATGATGGAACTGACTGCCCACCA GAGCAGTGTGGGCTCTGTTCTGCAGGCTGGCAACCAACTGATAACCCAAGGAACTCTGTCAGATGAAG AAGAATTTGAAATTCAGGAACAGATGACACTGCTGAATGCAAGATGGGAGGCTCTTAGGGTGGAGAGT ATGGACAGACAGTCTAGGCTGCATGATGTGCTGATGGAACTGCAGAAGAAGCAACTGCAGCAGCTCTC 77Attorney Docket No: 046192-000119WOPT AGCCTGGTTAACACTCACAGAGGAGAGAATTCAGAAGATGGAAACATGCCCACTGGATGATGATGTGA AATCTCTACAAAAGCTGCTAGAAGAACATAAAAGTTTGCAATCAGATCTTGAGGCTGAGCAGGTGAAA GTAAATTCACTAACTCACATGGTGGTTATTGTGGATGAAAACTCAGGTGAATCAGCAACAGCTATCCT AGAAGACCAGTTACAGAAACTTGGAGAGAGGTGGACAGCTGTATGCAGGTGGACTGAAGAAAGGTGGA ATAGATTACAAGAAATCAATATATTGTGGCAGGAATTATTGGAAGAACAGTGCTTGTTGAAAGCTTGG TTAACTGAAAAAGAAGAGGCCTTAAATAAAGTCCAGACAAGCAACTTCAAAGACCAAAAGGAACTAAG TGTGAGTGTTAGGAGGCTGGCTATTTTGAAGGAAGACATGGAAATGAAGAGGCAAACATTGGATCAGC TGAGTGAGATTGGCCAGGATGTGGGACAATTACTTGACAATTCCAAGGCATCTAAGAAGATCAACTCT GACAGTGAGGAACTGACTCAAAGATGGGATTCTTTGGTGCAGAGACTAGAGGATTCCTCCAACCAGGT GACTCAGGCTGTGGCAAAGCTGGGGATGTCTCAGATTCCTCAGAAGGACCTTCTGGAGACTGTTAGAG TAAGAGAACAAGCTATTACCAAAAAATCTAAGCAGGAACTGCCTCCTCCTCCACCCCCAAAGAAGAGG CAGATCCATGTGGATTTGGAAAAACTCAGAGACCTGCAGGGGGCTATGGATGACCTGGATGCAGACAT GAAGGAGGCAGAGAGTGTGAGAAATGGCTGGAAGCCAGTGGGAGACTTACTCATTGATTCCCTGCAGG ATCACATTGAAAAAATCATGGCATTTAGGGAAGAAATAGCCCCAATCAACTTTAAAGTTAAAACAGTG AATGACTTAAGCTCTCAGCTGTCACCCCTTGACCTGCATCCATCACTAAAGATGTCTAGGCAGCTAGA TGATCTTAATATGAGGTGGAAACTTTTACAGGTTAGTGTAGATGATAGGCTTAAACAGCTTCAGGAAG CCCACAGAGATTTTGGTCCATCCTCTCAGCATTTTCTCTCTACCTCTGTGCAGCTGCCTTGGCAAAGA TCCATTTCACATAATAAAGTGCCATATTACATCAACCATCAAACACAGACTACATGTTGGGACCATCC TAAAATGACAGAACTCTTTCAATCCCTTGCAGACCTGAATAATGTGAGGTTTTCAGCCTACAGAACTG CCATCAAAATCAGAAGACTACAAAAAGCACTATGTCTGGATCTCTTAGAGTTGAGTACCACCAATGAA ATTTTCAAACAGCACAAGTTGAACCAAAATGACCAGCTCCTCAGTGTCCCAGATGTCATCAACTGTCT GACTACAACTTATGATGGCCTTGAACAAATGCATAAGGACCTGGTCAATGTGCCACTCTGTGTGGACA TGTGTCTCAATTGGTTGCTCAATGTTTATGATACAGGTAGGACAGGAAAAATTAGGGTGCAGAGTCTG AAGATTGGATTAATGTCTCTCAGTAAAGGTCTCTTGGAAGAAAAATACAGATATCTCTTTAAGGAAGT TGCTGGGCCTACTGAAATGTGTGATCAGAGGCAGCTGGGCCTGTTACTTCATGATGCCATCCAGATCC CCAGGCAGCTGGGAGAGGTAGCAGCTTTTGGAGGCAGCAATATAGAGCCAAGTGTCAGGAGCTGCTTC CAACAGAATAACAATAAACCTGAAATATCAGTGAAAGAGTTTATAGATTGGATGCATTTGGAACCTCA GTCCATGGTTTGGCTCCCAGTTTTACATAGGGTGGCTGCAGCAGAGACTGCAAAACATCAGGCCAAAT GCAACATCTGTAAAGAATGTCCAATAGTAGGCTTCAGGTATAGGTCACTTAAGCATTTTAACTATGAT GTCTGCCAGAGTTGTTTCTTTAGTGGTAGAACTGCTAAAGGTCACAAATTACATTACCCAATGGTGGA ATATTGTATACCTACAACATCAGGTGAGGATGTGAGGGACTTCACAAAGGTACTTAAGAACAAGTTCA GGTCAAAGAAGTACTTTGCTAAACACCCAAGATTGGGTTACCTGCCTGTGCAGACAGTGTTAGAAGGT GACAACTTAGAGACTCAGGCCATGTGA

[0190] Prior art construct_[[US7771993B2]] (SEQ ID NO: 112)ATGGCCAAGTATGGAGAACATGAAGCCAGTCCTGACAATGGGCAGAACGAATTCAGTGATATCATTAA GTCCAGATCTGATGAACACAATGACGTACAGAAGAAAACCTTTACCAAATGGATAAATGCTCGATTTT CAAAGAGTGGGAAACCACCCATCAATGATATGTTCACAGACCTCAAAGATGGAAGGAAGCTATTGGAT CTTCTAGAAGGCCTCACAGGAACATCACTGCCAAAGGAACGTGGTTCCACAAGGGTACATGCCTTAAA TAACGTCAACAGAGTGCTGCAGGTTTTACATCAGAACAATGTGGAATTAGTGAATATAGGGGGAACTG ACATTGTGGATGGAAATCACAAACTGACTTTGGGGTTACTTTGGAGCATCATTTTGCACTGGCAGGTG AAAGATGTCATGAAGGATGTCATGTCGGACCTGCAGCAGACGAACAGTGAGAAGATCCTGCTCAGCTG GGTGCGTCAGACCACCAGGCCCTACAGCCAAGTCAACGTCCTCAACTTCACCACCAGCTGGACAGATG GACTCGCCTTTAATGCTGTCCTCCACCGACATAAACCTGATCTCTTCAGCTGGGATAAAGTTGTCAAA ATGTCACCAATTGAGAGACTTGAACATGCCTTCAGCAAGGCTCAAACTTATTTGGGAATTGAAAAGCT GTTAGATCCTGAAGATGTTGCCGTTCGGCTTCCTGACAAGAAATCCATAATTATGTATTTAACATCTT TGTTTGAGGTGCTACCTCAGCAAGTCACCATAGACGCCATCCGTGAGGTAGAGACACTCCCAAGGAAA TATAAAAAAGAATGTGAAGAAGAGGCAATTAATATACAGAGTACAGCGCCTGAGGAGGAGCATGAGAG TCCCCGAGCTGAAACTCCCAGCACTGTCACTGAGGTCGACATGGATCTGGACAGCTATCAGATTGCGT TGGAGGAAGTGCTGACCTGGTTGCTTTCTGCTGAGGACACTTTCCAGGAGCAGGATGATATTTCTGAT GATGTTGAAGAAGTCAAAGACCAGTTTGCAACCCATGAAGCTTTTATGATGGAACTGACTGCACACCA GAGCAGTGTGGGCAGCGTCCTGCAGGCAGGCAACCAACTGATAACACAAGGAACTCTGTCAGACGAAG AAGAATTTGAGATTCAGGAACAGATGACCCTGCTGAATGCTAGATGGGAGGCTCTTAGGGTGGAGAGT ATGGACAGACAGTCCCGGCTGCACGATGTGCTGATGGAACTGCAGAAGAAGCAACTGCAGCAGCTCTC 78Attorney Docket No: 046192-000119WOPT CGCCTGGTTAACACTCACAGAGGAGCGCATTCAGAAGATGGAAACTTGCCCCCTGGATGATGATGTAA AATCTCTACAAAAGCTGCTAGAAGAACATAAAAGTTTGCAAAGTGATCTTGAGGCTGAACAGGTGAAA GTAAATTCACTAACTCACATGGTGGTCATTGTTGATGAAAACAGTGGTGAGAGCGCTACAGCTATCCT AGAAGACCAGTTACAGAAACTTGGTGAGCGCTGGACAGCAGTATGCCGTTGGACTGAAGAACGCTGGA ATAGGTTACAAGAAATCAATATATTGTGGCAGGAATTATTGGAAGAACAGTGCTTGTTGAAAGCTTGG TTAACCGAAAAAGAAGAGGCTTTAAATAAAGTCCAGACAAGCAACTTCAAAGACCAAAAGGAACTAAG TGTCAGTGTTCGACGTCTGGCTATTTTGAAGGAAGACATGGAAATGAAGCGTCAAACATTGGATCAGC TGAGTGAGATTGGCCAGGATGTGGGACAATTACTTGATAATTCCAAGGCATCTAAGAAGATCAACAGT GACTCAGAGGAACTGACTCAAAGATGGGATTCTTTGGTTCAGAGACTAGAAGATTCCTCCAACCAGGT GACTCAGGCTGTAGCAAAGCTGGGGATGTCTCAGATTCCTCAGAAGGACCTTTTGGAGACTGTTCGTG TAAGAGAACAAGCAATTACAAAAAAATCTAAGCAGGAACTGCCTCCTCCTCCTCCCCCAAAGAAGAGA CAGATCCATGTGGATTTGGAGAAACTCAGAGACCTGCAGGGAGCTATGGATGACCTGGACGCTGACAT GAAGGAGGCAGAGTCCGTGCGGAATGGCTGGAAGCCCGTGGGAGACTTACTCATTGACTCGCTGCAGG ATCACATTGAAAAAATCATGGCATTTAGAGAAGAAATTGCACCAATCAACTTTAAAGTTAAAACGGTG AATGATTTATCCAGTCAGCTGTCTCCACTTGACCTGCATCCCTCTCTAAAGATGTCTCGCCAGCTAGA TGACCTTAATATGCGATGGAAACTTTTACAGGTTTCTGTGGATGATCGCCTTAAACAGCTTCAGGAAG CCCACAGAGATTTTGGACCATCCTCTCAGCATTTTCTCTCTACGTCAGTCCAGCTGCCGTGGCAAAGA TCCATTTCACATAATAAAGTGCCCTATTACATCAACCATCAAACACAGACCACCTGTTGGGACCATCC TAAAATGACCGAACTCTTTCAATCCCTTGCTGACCTGAATAATGTACGTTTTTCTGCCTACCGTACAG CAATCAAAATCCGAAGACTACAAAAAGCACTATGTTTGGATCTCTTAGAGTTGAGTACAACAAATGAA ATTTTCAAACAGCACAAGTTGAACCAAAATGACCAGCTCCTCAGTGTTCCAGATGTCATCAACTGTCT GACAACAACTTATGATGGACTTGAGCAAATGCATAAGGACCTGGTCAACGTTCCACTCTGTGTTGATA TGTGTCTCAATTGGTTGCTCAATGTCTATGACACGGGTCGAACTGGAAAAATTAGAGTGCAGAGTCTG AAGATTGGATTAATGTCTCTCTCCAAAGGTCTCTTGGAAGAAAAATACAGATATCTCTTTAAGGAAGT TGCGGGGCCGACAGAAATGTGTGACCAGAGGCAGCTGGGCCTGTTACTTCATGATGCCATCCAGATCC CCCGGCAGCTAGGTGAAGTAGCAGCTTTTGGAGGCAGTAATATTGAGCCTAGTGTTCGCAGCTGCTTC CAACAGAATAACAATAAACCAGAAATAAGTGTGAAAGAGTTTATAGATTGGATGCATTTGGAACCACA GTCCATGGTTTGGCTCCCAGTTTTACATCGAGTGGCAGCAGCGGAGACTGCAAAACATCAGGCCAAAT GCAACATCTGTAAAGAATGTCCAATTGTCGGGTTCAGGTATAGAAGCCTTAAGCATTTTAACTATGAT GTCTGCCAGAGTTGTTTCTTTTCGGGTCGAACAGCAAAAGGTCACAAATTACATTACCCAATGGTGGA ATATTGTATACCTACAACATCTGGGGAAGATGTACGAGACTTCACAAAGGTACTTAAGAACAAGTTCA GGTCGAAGAAGTACTTTGCCAAACACCCTCGACTTGGTTACCTGCCTGTCCAGACAGTTCTTGAAGGT GACAACTTAGAGACTTGA

[0191] wt_human (SEQ ID NO: 113)ATGGCCAAGTATGGAGAACATGAAGCCAGTCCTGACAATGGGCAGAACGAATTCAGTGATATCATTAA GTCCAGATCTGATGAACACAATGACGTACAGAAGAAAACCTTTACCAAATGGATAAATGCTCGATTTT CAAAGAGTGGGAAACCACCCATCAATGATATGTTCACAGACCTCAAAGATGGAAGGAAGCTATTGGAT CTTCTAGAAGGCCTCACAGGAACATCACTGCCAAAGGAACGTGGTTCCACAAGGGTACATGCCTTAAA TAACGTCAACAGAGTGCTGCAGGTTTTACATCAGAACAATGTGGAATTAGTGAATATAGGGGGAACTG ACATTGTGGATGGAAATCACAAACTGACTTTGGGGTTACTTTGGAGCATCATTTTGCACTGGCAGGTG AAAGATGTCATGAAGGATGTCATGTCGGACCTGCAGCAGACGAACAGTGAGAAGATCCTGCTCAGCTG GGTGCGTCAGACCACCAGGCCCTACAGCCAAGTCAACGTCCTCAACTTCACCACCAGCTGGACAGATG GACTCGCCTTTAATGCTGTCCTCCACCGACATAAACCTGATCTCTTCAGCTGGGATAAAGTTGTCAAA ATGTCACCAATTGAGAGACTTGAACATGCCTTCAGCAAGGCTCAAACTTATTTGGGAATTGAAAAGCT GTTAGATCCTGAAGATGTTGCCGTTCAGCTTCCTGACAAGAAATCCATAATTATGTATTTAACATCTT TGTTTGAGGTGCTACCTCAGCAAGTCACCATAGACGCCATCCGTGAGGTAGAGACACTCCCAAGGAAA TATAAAAAAGAATGTGAAGAAGAGGCAATTAATATACAGAGTACAGCGCCTGAGGAGGAGCATGAGAG TCCCCGAGCTGAAACTCCCAGCACTGTCACTGAGGTTGACATGGATCTGGACAGCTATCAGATTGCGT TGGAGGAAGTGCTGACCTGGTTGCTTTCTGCTGAGGACACTTTCCAGGAGCAGGATGATATTTCTGAT GATGTTGAAGAAGTCAAAGACCAGTTTGCAACCCATGAAGCTTTTATGATGGAACTGACTGCACACCA GAGCAGTGTGGGCAGCGTCCTGCAGGCAGGCAACCAACTGATAACACAAGGAACTCTGTCAGACGAAG AAGAATTTGAGATTCAGGAACAGATGACCCTGCTGAATGCTAGATGGGAGGCTCTTAGGGTGGAGAGT ATGGACAGACAGTCCCGGCTGCACGATGTGCTGATGGAACTGCAGAAGAAGCAACTGCAGCAGCTCTC 79Attorney Docket No: 046192-000119WOPT CGCCTGGTTAACACTCACAGAGGAGCGCATTCAGAAGATGGAAACTTGCCCCCTGGATGATGATGTAA AATCTCTACAAAAGCTGCTAGAAGAACATAAAAGTTTGCAAAGTGATCTTGAGGCTGAACAGGTGAAA GTAAATTCACTAACTCACATGGTGGTCATTGTTGATGAAAACAGTGGTGAGAGTGCTACAGCTATCCT AGAAGACCAGTTACAGAAACTTGGTGAGCGCTGGACAGCAGTATGCCGTTGGACTGAAGAACGCTGGA ATAGGTTACAAGAAATCAATATATTGTGGCAGGAATTATTGGAAGAACAGTGCTTGTTGAAAGCTTGG TTAACCGAAAAAGAAGAGGCTTTAAATAAAGTCCAGACAAGCAACTTCAAAGACCAAAAGGAACTAAG TGTCAGTGTTCGACGTCTGGCTATTTTGAAGGAAGACATGGAAATGAAGCGTCAAACATTGGATCAGC TGAGTGAGATTGGCCAGGATGTGGGACAATTACTTGATAATTCCAAGGCATCTAAGAAGATCAACAGT GACTCAGAGGAACTGACTCAAAGATGGGATTCTTTGGTTCAGAGACTAGAAGATTCCTCCAACCAGGT GACTCAGGCTGTAGCAAAGCTGGGGATGTCTCAGATTCCTCAGAAGGACCTTTTGGAGACTGTTCGTG TAAGAGAACAAGCAATTACAAAAAAATCTAAGCAGGAACTGCCTCCTCCTCCTCCCCCAAAGAAGAGA CAGATCCATGTGGATTTGGAGAAACTCAGAGACCTGCAGGGAGCTATGGATGACCTGGACGCTGACAT GAAGGAGGCAGAGTCCGTGCGGAATGGCTGGAAGCCCGTGGGAGACTTACTCATTGACTCGCTGCAGG ATCACATTGAAAAAATCATGGCATTTAGAGAAGAAATTGCACCAATCAACTTTAAAGTTAAAACGGTG AATGATTTATCCAGTCAGCTGTCTCCACTTGACCTGCATCCCTCTCTAAAGATGTCTCGCCAGCTAGA TGACCTTAATATGCGATGGAAACTTTTACAGGTTTCTGTGGATGATCGCCTTAAACAGCTTCAGGAAG CCCACAGAGATTTTGGACCATCCTCTCAGCATTTTCTCTCTACGTCAGTCCAGCTGCCGTGGCAAAGA TCCATTTCACATAATAAAGTGCCCTATTACATCAACCATCAAACACAGACCACCTGTTGGGACCATCC TAAAATGACCGAACTCTTTCAATCCCTTGCTGACCTGAATAATGTACGTTTTTCTGCCTACCGTACAG CAATCAAAATCCGAAGACTACAAAAAGCACTATGTTTGGATCTCTTAGAGTTGAGTACAACAAATGAA ATTTTCAAACAGCACAAGTTGAACCAAAATGACCAGCTCCTCAGTGTTCCAGATGTCATCAACTGTCT GACAACAACTTATGATGGACTTGAGCAAATGCATAAGGACCTGGTCAACGTTCCACTCTGTGTTGATA TGTGTCTCAATTGGTTGCTCAATGTCTATGACACGGGTCGAACTGGAAAAATTAGAGTGCAGAGTCTG AAGATTGGATTAATGTCTCTCTCCAAAGGTCTCTTGGAAGAAAAATACAGATATCTCTTTAAGGAAGT TGCAGGGCCAACAGAAATGTGTGACCAGAGGCAGCTGGGCCTGTTACTTCATGATGCCATCCAGATCC CCCGGCAGCTAGGTGAAGTAGCAGCTTTTGGAGGCAGTAATATTGAGCCTAGTGTTCGCAGCTGCTTC CAACAGAATAACAATAAACCAGAAATAAGTGTGAAAGAGTTTATAGATTGGATGCATTTGGAACCACA GTCCATGGTTTGGCTCCCAGTTTTACATCGAGTGGCAGCAGCGGAGACTGCAAAACATCAGGCCAAAT GCAACATCTGTAAAGAATGTCCAATTGTCGGGTTCAGGTATAGAAGCCTTAAGCATTTTAACTATGAT GTCTGCCAGAGTTGTTTCTTTTCGGGTCGAACAGCAAAAGGTCACAAATTACATTACCCAATGGTGGA ATATTGTATACCTACAACATCTGGGGAAGATGTACGAGACTTCACAAAGGTACTTAAGAACAAGTTCA GGTCGAAGAAGTACTTTGCCAAACACCCTCGACTTGGTTACCTGCCTGTCCAGACAGTTCTTGAAGGT GACAACTTAGAGACTCAGGCAATGTGA Nucleic Acids

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

[0193] In some embodiments of any of the aspects, the nucleic acid comprises a sequence with atleast 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 with 80Attorney Docket No: 046192-000119WOPT at 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 atleast 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 the 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 atleast 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 with 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 atleast 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 the 81Attorney Docket No: 046192-000119WOPT aspects, 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 whichis codon-optimized for expression in human cells.

[0198] In some embodiments of any of the aspects, the portion of the nucleic acid encoding theutrophin 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 theutrophin 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 GCTGGACCCCGAGGACGTGG CCGTGCAGCTGCCCGACAAGAAGTCCATCATCATGTAC

[0201] In some embodiments of any of the aspects, the portion of the nucleic acid encoding theutrophin 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 domain82Attorney Docket No: 046192-000119WOPT ATGGCCAAGTACGGCGAGCACGAGGCCTCCCCCGACAACGGCCAGAACGAGTTCTCCGACATCATCAA GTCCCGCTCCGACGAGCACAACGACGTGCAGAAGAAGACCTTCACCAAGTGGATCAACGCCCGCTTCT CCAAGTCCGGCAAGCCCCCCATCAACGACATGTTCACCGACCTGAAGGACGGCCGCAAGCTGCTGGAC CTGCTGGAGGGCCTGACCGGCACCTCCCTGCCCAAGGAGCGCGGCTCCACCCGCGTGCACGCCCTGAA CAACGTGAACCGCGTGCTGCAGGTGCTGCACCAGAACAACGTGGAGCTGGTGAACATCGGCGGCACCG ACATCGTGGACGGCAACCACAAGCTGACCCTGGGCCTGCTGTGGTCCATCATCCTGCACTGGCAGGTG AAGGACGTGATGAAGGACGTGATGTCCGACCTGCAGCAGACCAACTCCGAGAAGATCCTGCTGTCCTG GGTGCGCCAGACCACCCGCCCCTACTCCCAGGTGAACGTGCTGAACTTCACCACCTCCTGGACCGACG GCCTGGCCTTCAACGCCGTGCTGCACCGCCACAAGCCCGACCTGTTCTCCTGGGACAAGGTGGTGAAG ATGTCCCCCATCGAGCGCCTGGAGCACGCCTTCTCCAAGGCCCAGACCTACCTGGGCATCGAGAAGCT GCTGGACCCCGAGGACGTGG CCGTGCAGCTGCCCGACAAGAAGTCCATCATCATGTACCTGACCTCCCTGTTCGAGGTGCTGCCCCAG CAGGTGACCATCGACGCCATCCGCGAGGTGGAG

[0203] In some embodiments of any of the aspects, the portion of the nucleic acid encoding theutrophin 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 theutrophin 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 GGTGAGGCAGACCACCAGGCCTTACTCCCAGGTGAACGTGCTGAACTTCACCACCTCCTGGACCGACG 83Attorney Docket No: 046192-000119WOPT GCCTGGCCTTCAACGCCGTGCTGCACAGGCACAAGCCTGACCTGTTCTCCTGGGACAAGGTGGTGAAG ATGTCCCCTATCGAGAGGCTGGAGCACGCCTTCTCCAAGGCCCAGACCTACCTGGGCATCGAGAAGCT GCTGGACCCTGAGGACGTGGCCGTGCAGCTGCCTGACAAGAAGTCCATCATCATGTACCTGACCTCCC TGTTCGAGGTGCTGCCTCAGCAGGTGACCATCGACGCCATCAGGGAGGTGGAG

[0207] In some embodiments of any of the aspects, the portion of the nucleic acid encoding theutrophin 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 theutrophin 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 84Attorney Docket No: 046192-000119WOPT

[0211] In some embodiments of any of the aspects, the portion of the nucleic acid encoding theutrophin 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 theutrophin 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 theutrophin 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%, 85Attorney Docket No: 046192-000119WOPT 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 theutrophin 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 theutrophin 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 NT86Attorney Docket No: 046192-000119WOPT ATGGCTAAGTATGGGGAACATGAGGCCAGTCCAGACAATGGGCAGAATGAATTCTCTGATATCATTAA 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 theutrophin 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 theutrophin 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 ATATTGTGGATGGCAATCACAAACTGACTTTGGGGTTACTTTGGAGTATCATTTTGCACTGGCAGGTG 87Attorney Docket No: 046192-000119WOPT AAAGATGTTATGAAGGATGTGATGTCTGACCTGCAGCAGACCAACTCAGAGAAGATCCTGCTCAGCTG GGTGAGGCAGACCACTAGGCCATACTCCCAAGTCAATGTGCTCAACTTCACCACCTCCTGGACAGATG GCCTTGCCTTTAATGCTGTCCTCCACAGACATAAACCTGATCTCTTCAGCTGGGATAAAGTTGTCAAA ATGTCACCAATTGAGAGGCTTGAACATGCCTTCAGCAAGGCCCAAACTTATTTGGGAATTGAAAAGCT GTTAGATCCTGAAGATGTGGCTGTGCAGCTTCCAGACAAGAAATCCATAATTATGTATTTAACATCTT TGTTTGAGGTGCTACCTCAGCAAGTCACAATTGATGCTATCAGAGAGGTAGAG

[0225] In some embodiments of any of the aspects, the portion of the nucleic acid encoding theutrophin 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 theutrophin 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 theutrophin 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 theutrophin 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 88Attorney Docket No: 046192-000119WOPT

[0232] In some embodiments of any of the aspects, the portion of the nucleic acid encoding theutrophin 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 theutrophin 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 theutrophin 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 domainACCCTCCCAAGGAAATATAAAAAAGAATGTGAGGAAGAGGCCATTAATATACAGTCCACAGCACCAGA GGAGGAGCATGAGAGTCCCAGGGCTGAAACTCCCAGCACT

[0238] In some embodiments of any of the aspects, the portion of the nucleic acid encoding theutrophin 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 89Attorney Docket No: 046192-000119WOPT

[0240] In some embodiments of any of the aspects, the portion of the nucleic acid encoding theutrophin 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 theutrophin 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 domainACCCTCCCAAGGAAATATAAAAAAGAATGTGAGGAAGAGGCAATTAATATACAGTCTACTGCTCCTGA GGAGGAGCATGAGAGTCCCAGAGCAGAAACTCCCAGCACA

[0244] In some embodiments of any of the aspects, the portion of the nucleic acid encoding theutrophin 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 domainACTCTCCCAAGGAAATATAAAAAAGAATGTGAGGAAGAGGCAATTAATATACAGTCCACAGCCCCTGA GGAGGAGCATGAGAGTCCCAGAGCTGAGACTCCCAGCACA

[0246] In some embodiments of any of the aspects, the portion of the nucleic acid encoding theutrophin 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 domain90Attorney Docket No: 046192-000119WOPT ACACTCCCTAGGAAATATAAAAAAGAATGTGAAGAAGAGGCAATTAATATACAGAGTACAGCCCCAGA AGAGGAGCATGAGAGTCCCAGGGCTGAGACTCCCAGCACT

[0248] In some embodiments of any of the aspects, the portion of the nucleic acid encoding theutrophin 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 theutrophin 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 theutrophin 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 theutrophin 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. 91Attorney Docket No: 046192-000119WOPT

[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 theutrophin 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 theutrophin 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 theutrophin 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-optimized sequence of SEQ ID NO: 430.

[0260] SEQ ID NO: 430 Codon-optimized sequence encoding utrophin SLR1 domainGATAGCTATCAGATTGCTTTGGAGGAAGTGCTGACCTGGTTGCTTTCTGCAGAAGACACTTTCCAGGA GCAGGATGACATTTCTGATGATGTTGAAGAAGTCAAAGACCAGTTTGCCACCCATGAGGCATTTATGA 92Attorney Docket No: 046192-000119WOPT TGGAACTGACTGCCCACCAGTCCTCTGTGGGCTCTGTGCTGCAGGCAGGCAACCAACTGATAACTCAA GGAACACTGTCAGATGAAGAAGAATTTGAGATTCAGGAACAGATGACACTGCTGAATGCTAGATGGGA GGCCCTTAGGGTGGAGAGCATGGACAGGCAGTCCAGGCTGCAT

[0261] In some embodiments of any of the aspects, the portion of the nucleic acid encoding theutrophin 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 theutrophin 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 theutrophin 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 93Attorney Docket No: 046192-000119WOPT

[0267] In some embodiments of any of the aspects, the portion of the nucleic acid encoding theutrophin 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 GGCTCTTA GGGTGGAGAGTATGGACAGGCAGTCCAGACTGCAT

[0269] In some embodiments of any of the aspects, the portion of the nucleic acid encoding theutrophin 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 theutrophin 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 94Attorney Docket No: 046192-000119WOPT

[0273] In some embodiments of any of the aspects, the portion of the nucleic acid encoding theutrophin 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 GGAACTCTGTCAGATGAAGAAGAATTTGAAATTCAGGAACAGATGACACTGCTGAATGCAAGATGGGA GGCTCTTAGGGTGGAGAGTATGGACAGACAGTCTAGGCTGCAT

[0275] In some embodiments of any of the aspects, the portion of the nucleic acid encoding theutrophin 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 theutrophin 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 theutrophin 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 95Attorney Docket No: 046192-000119WOPT

[0280] In some embodiments of any of the aspects, the portion of the nucleic acid encoding theutrophin 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 theutrophin 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 theutrophin 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 GATGGAAACTTGCCCCCTGGATGATGATGTCAAATCTCTACAAAAGCTGCTAGAAGAACATAAAAGTT TGCAATCTGACCTTGAGGCTGAACAGGTGAAAGTAAATTCACTAACTCACATGGTGGTGATTGTGGAT GAGAACAGTGGTGAGAGTGCTACTGCTATCCTAGAAGACCAGTTACAGAAACTTGGAGAGAGGTGGAC AGCAGTATGCAGGTGGACTGAGGAAAGGTGGAATAGATTACAA

[0286] In some embodiments of any of the aspects, the portion of the nucleic acid encoding theutrophin 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%, 96Attorney Docket No: 046192-000119WOPT 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 GATGGAAACTTGCCCCCTGGATGATGATGTAAAATCTCTACAAAAGCTGCTAGAAGAACATAAAAGTT TGCAAAGTGATCTTGAGGCTGAACAGGTGAAAGTAAATTCACTAACTCACATGGTGGTCATAGTTGAT GAGAACTCAGGTGAGAGTGCCACAGCTATCCTAGAAGACCAGTTACAGAAACTGGGTGAGAGATGGAC TGCAGTCTGCAGGTGGACAGAAGAAAGGTGGAATAGGTTACAA

[0288] In some embodiments of any of the aspects, the portion of the nucleic acid encoding theutrophin 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 domainGAACTGCAGAAGAAGCAACTGCAGCAGCTCTCTGCTTGGTTAACACTCACAGAGGAGAGGATTCAGAA GATGGAAACTTGCCCCCTGGATGATGATGTAAAATCTCTACAAAAGCTGCTAGAAGAACATAAAAGTT TGCAAAGTGACCTTGAGGCAGAGCAGGTGAAAGTAAATTCACTAACTCACATGGTGGTCATTGTTGAT GAAAACTCAGGGGAGTCAGCTACAGCTATCCTAGAAGACCAGTTACAGAAATTGGGTGAGAGGTGGAC AGCTGTATGCAGGTGGACTGAGGAAAGGTGGAATAGGTTACAA

[0290] In some embodiments of any of the aspects, the portion of the nucleic acid encoding theutrophin 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 domainGAACTGCAGAAGAAGCAACTGCAGCAGCTCTCAGCATGGTTAACACTCACAGAGGAGAGGATTCAGAA GATGGAAACTTGCCCCCTGGATGATGATGTGAAATCTCTACAAAAGCTGCTAGAAGAACATAAAAGTT TGCAATCAGATCTTGAGGCTGAACAGGTGAAAGTAAATTCACTAACTCACATGGTGGTGATTGTGGAT GAGAACTCAGGGGAGAGTGCTACAGCAATCCTAGAAGACCAGTTACAGAAACTGGGGGAGAGATGGAC AGCAGTCTGCAGGTGGACAGAGGAAAGATGGAATAGGTTACAA

[0292] In some embodiments of any of the aspects, the portion of the nucleic acid encoding theutrophin 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. 97Attorney Docket No: 046192-000119WOPT

[0293] SEQ ID NO: 447 Codon-optimized sequence encoding utrophin SLR2 domainGAACTGCAGAAGAAGCAACTGCAGCAGCTCTCAGCCTGGTTAACACTCACAGAGGAGAGAATTCAGAA GATGGAAACCTGCCCACTGGATGATGATGTGAAATCTCTACAAAAGCTGCTAGAAGAACATAAAAGTT TGCAATCTGACCTTGAGGCTGAACAGGTGAAAGTAAATTCACTAACTCACATGGTGGTCATTGTAGAT GAGAACAGTGGGGAGAGTGCCACAGCTATCCTAGAAGACCAGTTACAGAAACTTGGGGAGAGATGGAC TGCAGTGT GCAGGTGGACTGAGGAAAGGTGGAATAGATTACAA

[0294] In some embodiments of any of the aspects, the portion of the nucleic acid encoding theutrophin 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 GATGGAAACCTGCCCTCTGGATGATGATGTCAAATCTCTACAAAAGCTGCTAGAAGAACATAAAAGTT TGCAATCTGATCTTGAGGCTGAACAGGTGAAAGTAAATTCACTAACTCACATGGTGGTGATTGTTGAT GAAAACAGTGGAGAGAGTGCAACAGCTATCCTAGAAGACCAGTTACAGAAACTTGGTGAGAGGTGGAC TGCAGTCT GCAGATGGACAGAAGAAAGATGGAATAGGTTACAA

[0296] In some embodiments of any of the aspects, the portion of the nucleic acid encoding theutrophin 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 domainGAACTGCAGAAGAAGCAACTGCAGCAGCTCAGTGCTTGGTTAACACTCACAGAGGAGAGAATTCAGAA GATGGAAACCTGCCCCCTGGATGATGATGTCAAATCTCTACAAAAGCTGCTAGAAGAACATAAAAGTT TGCAATCAGATCTTGAGGCTGAGCAGGTGAAAGTAAATTCACTAACTCACATGGTGGTCATTGTTGAT GAAAACAGTGGTGAGAGTGCTACAGCCATCCTAGAAGACCAGTTACAGAAACTTGGAGAGAGGTGGAC TGCAGTATGCAGATGGACAGAAGAAAGATGGAATAGGTTACAA

[0298] In some embodiments of any of the aspects, the portion of the nucleic acid encoding theutrophin 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. 98Attorney Docket No: 046192-000119WOPT

[0299] SEQ ID NO: 450 Codon-optimized sequence encoding utrophin SLR2 domainGAACTGCAGAAGAAGCAACTGCAGCAGCTCTCAGCCTGGTTAACACTCACAGAGGAGAGAATTCAGAA GATGGAAACATGCCCACTGGATGATGATGTGAAATCTCTACAAAAGCTGCTAGAAGAACATAAAAGTT TGCAATCAGATCTTGAGGCTGAGCAGGTGAAAGTAAATTCACTAACTCACATGGTGGTTATTGTGGAT GAAAACTCAGGTGAATCAGCAACAGCTATCCTAGAAGACCAGTTACAGAAACTTGGAGAGAGGTGGAC AGCTGTATGCAGGTGGACTGAAGAAAGGTGGAATAGATTACAA

[0300] In some embodiments of any of the aspects, the portion of the nucleic acid encoding theutrophin 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 theutrophin 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 theutrophin 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 theutrophin 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, the 99Attorney Docket No: 046192-000119WOPT portion 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 theutrophin 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 theutrophin 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 AGGAAGACATGGAAATGAAGAGGCAAACATTGGATCAGCTGAGTGAGATAGGTCAGGATGTGGGACAA TTACTTGATAATTCCAAGGCTTCTAAGAAGATCAACTCAGACAGTGAGGAACTGACTCAAAGGTGGGA TTCTTTGGTTCAGAGACTAGAAGATTCCTCCAACCAGGTGACT

[0311] In some embodiments of any of the aspects, the portion of the nucleic acid encoding theutrophin 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 domain100Attorney Docket No: 046192-000119WOPT CAGGAATTATTGGAAGAACAGTGCTTGTTGAAAGCATGGTTAACTGAAAAAGAAGAGGCTTTAAATAA AGTCCAGACAAGCAACTTCAAAGACCAAAAGGAACTAAGTGTCAGTGTTAGGAGGCTGGCTATTTTGA AGGAAGACATGGAAATGAAGAGACAAACATTGGATCAGCTGAGTGAGATAGGCCAGGATGTGGGACAA TTACTTGATAATTCCAAGGCCTCTAAGAAGATCAACTCAGATTCAGAGGAACTGACTCAAAGGTGGGA TTCCTTGGTTCAGAGACTAGAAGATTCCTCCAACCAGGTGACT

[0313] In some embodiments of any of the aspects, the portion of the nucleic acid encoding theutrophin 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 AGGAAGACATGGAAATGAAGAGACAAACATTGGATCAGCTGTCAGAGATAGGGCAGGATGTGGGACAA TTACTTGATAATTCCAAGGCATCTAAGAAGATCAACTCAGACTCAGAGGAACTGACTCAAAGGTGGGA TTCCTTGGTTCAGAGACTAGAAGATTCCTCCAACCAGGTGACT

[0315] In some embodiments of any of the aspect...

Claims

Attorney Docket No: 046192-000119WOPT 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; andk) a dystrophin cysteine rich (CR) domain.

2. The polypeptide of any one of the preceding claims, wherein the polypeptide further comprises autrophin 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 adystrophin SLR 23 domain.

5. The polypeptide of any one of the preceding claims, wherein the polypeptide further comprises autrophin 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 adystroglycan binding domain. 267Attorney Docket No: 046192-000119WOPT7. The polypeptide of any one of the preceding claims, wherein the polypeptide further comprises adomain 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 adomain 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 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; andl) a dystroglycan 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;268Attorney Docket No: 046192-000119WOPT 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; andm) a dystroglycan 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;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; andm) a dystroglycan 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;269Attorney Docket No: 046192-000119WOPT 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 506and / or o) sequences having at least 85%, at least 90%, at least 95% or greater sequence identityto any of the foregoing sequences.

13. The polypeptide of any one of the preceding claims, comprising the sequence of one of SEQ IDNOs: 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 compriseany of: a) a dystrophin SLR4 – SLR19 domain;b) a utrophin SLR4-SLR19 domain;c) a dystrophin hinge 3 domain; andd) a utrophin hinge 3 domain.

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

19. The polypeptide of any one of the preceding claims, wherein the polypeptide does not compriseany 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; ande) a dystrophin hinge 3 domain.

20. The polypeptide of any one of the preceding claims, wherein the polypeptide does not compriseany 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; and270Attorney Docket No: 046192-000119WOPT e) a dystrophin hinge 2 domain.

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

22. The polypeptide of any one of the preceding claims, wherein the polypeptide does not compriseany 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; andg) 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 sequencehaving 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 acodon-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 SLRdomain 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 utrophinhinge 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 groupconsisting 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 aSPc5-12 promoter. 271Attorney Docket No: 046192-000119WOPT32. The nucleic acid of claim 29, wherein the muscle-specific promoter is a SP0524 promoter or aSP0527 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 ofone 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 ofone 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 regulatoryelements and / or a polyA sequence.

38. The nucleic acid of claim 37, wherein the muscle-specific promoter is a SP0524 promoter and thepolyA 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 selectedfrom 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 SEQID 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; ande) 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 groupconsisting of: SP0524; SPc5-12; SP0525; SP0526; SP0527; SP0528; SCP1; and CRE0053.

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

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

48. The vector of claim 44, wherein the muscle-specific promoter comprises the sequence of one ofSEQ ID NOs: 18, 20, 24, 25, 26, 27, 28, or 29. 272Attorney Docket No: 046192-000119WOPT49. 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 the vector is an AAV vector.

51. A recombinant adeno-associated virus (rAAV) vector comprising in its genome the nucleic acid ofany 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; andf) located between the 5’ and 3’ ITRs, the nucleic acid specified in any one of claims23-41.

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; andl) 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; f) a 3’ ITR.

55. The rAAV vector of any one of claims 51-54, wherein the intron is selected from the groupconsisting 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’ITRcomprises 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 areremoved.

58. The rAAV vector of any one of claims 51-57, wherein the poly A sequence is a full length SV40polyA 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 IDNO: 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 SP0524promoter and the polyA sequence is the sequence of SEQ ID NO:

52. 273Attorney Docket No: 046192-000119WOPT61. The rAAV vector of any one of claims 51-60, wherein the rAAV vector is a chimeric AAVvector, 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 haploidcapsid, 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 AAVserotype selected from the group consisting of: AAV1, AAV2, AAV3, AAV4, AAV5, AAV6, AAV7, AAV8, AAV9, AAV10, AAV11, AAV12, AAV13, AAVrh74, AAVrh10, po1, AAV9-PHP.B, AAV9-ePHP.B, AAV LK03, AAV Anc80L65, AAVDJ, AAV1A6ii, AAV1P5ii, AAV4A1ii, AAV7P4i, AAV9A1i, AAV9A2i, AAV9A6i, AAV9P1i, AAV9P2i, AAV9P5i, AAVrh10A1i, AAVrh10A2i, AAVrh10P1i, AAV12P2ii, AAVS10P1i, AAV JEA, AAV23xA P2i, AAVDJ P2i, AAV 2i8, AAV2G9, AAV2.5i82g9, AAV2.5, AAVr10pLDB_L2, AAVr10pLDB_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 AAVserotype 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 apharmaceutically acceptable carrier.

66. A method of treating Duchenne Muscular Dystrophy (DMD) in a subject in need thereof, themethod 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 rangeof 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 compositionof 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, autrophin SLR domain 2, a utrophin SLR domain 3, wherein the microutrophin polypeptide is encoded by a codon optimized nucleic acid sequence. 274Attorney Docket No: 046192-000119WOPT76. The microutrophin polypeptide of claim 75, further comprising utrophin hinge domain 1, utrophinhinge domain 2, and utrophin hinge domain 4.

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

78. The microutrophin polypetide of claim 75, wherein the codon optimized nucleic acid sequence isat 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 ofone 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 ofone 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 ofany 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.275

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