IP Library › Granted Patent US 12,263,230
Granted Patent B2
US 12,263,230 · App. 16/966,407 · Granted Apr 1, 2025

Gene therapy for limb-girdle muscular dystrophy type 2C

Inventor: Louise R. Rodino-Klapac (Columbus, OH)
Assignee: Research Institute at Nationwide Children's Hospital
A61K48/005A61K48/0075A61P21/00C07K14/4707C12N15/86A61K45/06
View Patent ↗
Loading inventors, assignments & file history…
Monitor This Case
Get email alerts when status or documents change.
Order Certified Copies
Most orders are placed with the USPTO same day — all within 24 business hours.
Order via The Patent Place →
Pre-filled with this patent's details
Quick Facts
Patent No.
US 12,263,230
App. No.
16/966,407
Granted
Apr 1, 2025
Kind
B2
Abstract

The disclosure relates to gene therapy vectors, such as AAV vectors, comprising a polynucleotide encoding γ-sarcoglycan (SGCG) and methods of using such gene therapy vectors to treat subjects suffering from a muscular dystrophy, e.g. limb girdle dystrophy type 2C (LGMD2C).

Claims (17)

1. A recombinant AAV (rAAV) vector comprising an AAV capsid and a gene expression cassette comprising a polynucleotide sequence encoding γ-sarcoglycan and a muscle specific control element, wherein the polynucleotide sequence encoding γ-sarcoglycan is under the transcriptional control of the muscle specific control element, wherein the polynucleotide sequence comprises a nucleotide sequence at least 95% identical to SEQ ID NO: 1 or SEQ ID NO: 3.

2. The rAAV vector of claim 1 , wherein the rAAV vector: comprises a self-complementary AAV vector genome; comprises a genome lacking AAV rep and cap DNA; is of the serotype AAV1, AAV2, AAV4, AAVS, AAV6, AAV, AAV8, AAVO, AAVIO, AAVI11, AAV12, AAV13, AAV rh74, or a variant thereof.

3. The rAAV vector of claim 2 , wherein the rAAV vector is of the AAV rh74 serotype and comprises the amino acid sequence set forth in SEQ ID NO:10.

4. The rAAV vector of claim 1 , wherein the polynucleotide encoding γ-sarcoglycan is operatively linked to the muscle-specific control element.

5. The rAAV vector of claim 4 , wherein the muscle-specific control element is selected from the group consisting of human skeletal actin gene element, cardiac actin gene element, myocyte-specific enhancer binding factor mef element, muscle creatine kinase (MCK) promoter, truncated MCK (tMCK) promoter, myosin heavy chain (MHC) element, MHCK7 promoter, C5-12, murine creatine kinase enhancer element, skeletal fast-twitch troponin c gene element, slow-twitch cardiac troponin c gene element, the slow-twitch troponin I gene element, hypoxia-inducible nuclear factors, steroid-inducible element, and glucocorticoid response element (gre).

6. The rAAV vector of claim 1 , wherein the muscle specific control element is an MHCK7 promoter.

7. The rAAV vector of claim 6 , wherein the MHCK promoter comprises the nucleotide sequence set forth in SEQ ID NO: 4.

8. The rAAV vector of claim 1 , wherein the rAAV vector comprises an intron comprising the nucleotide sequence set forth in SEQ ID NO: 5.

9. The rAAV vector of claim 1 , wherein the polynucleotide sequence encoding γ-sarcoglycan comprises a nucleotide sequence at least 95% identical to SEQ ID NO: 1 encodes the amino acid sequence of SEQ ID NO: 2.

10. A method of treating γ-sarcoglycanopathy in a subject, comprising administering to the subject a therapeutically effective amount of a recombinant adeno-associated virus (AAV) vector of claim 1 .

11. The rAAV vector of claim 1 , wherein the polynucleotide sequence encoding γ-sarcoglycan comprises the nucleotide sequence set forth in SEQ ID NO: 1.

12. The rAAV vector of claim 1 , wherein the capsid is of the serotype AAV1, AAV2, AAV4, AAV5, AAV6, AAV7, AAV8, AAV9, AAV10, AAV11, AAV12, AAV13, AAV rh74, or a variant thereof.

13. A composition comprising the rAAV vector of claim 1 .

14. A host cell, comprising an rAAV vector of claim 1 .

15. A combination therapy, comprising the composition of claim 13 and a corticosteroid.

16. A kit, comprising the composition of claim 13 and a corticosteroid.

17. The rAAV vector of claim 1 , wherein the polynucleotide sequence encoding γ-sarcoglycan comprises the nucleotide sequence set forth in SEQ ID NO: 3.

Assignments (1)
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Oct 19, 2020
From: RODINO-KLAPAC, LOUISE R.
To: RESEARCH INSTITUTE AT NATIONWIDE CHILDREN'S HOSPITAL
Reel/Frame 054098/0642 →
Continuity (2)
Provisional Application 62624616 · Jan 31, 2018
Related Publication 20200360534A1 · Nov 19, 2020
References Cited (400)
US 5173414A · Lebkowski et al. · 1992 [cited by applicant]
US 5449616A · Campbell et al. · 1995 [cited by applicant]
US 5658776A · Flotte et al. · 1997 [cited by applicant]
US 5672694A · Campbell et al. · 1997 [cited by applicant]
US 5786211A · Johnson · 1998 [cited by applicant]
US 5871982A · Wilson et al. · 1999 [cited by applicant]
US 6204059B1 · Samulski et al. · 2001 [cited by applicant]
US 6258595B1 · Gao et al. · 2001 [cited by applicant]
US 6262035B1 · Campbell et al. · 2001 [cited by applicant]
US 6566118B1 · Atkinson et al. · 2003 [cited by applicant]
US 6632800B1 · Russell et al. · 2003 [cited by applicant]
US 7282199B2 · Gao et al. · 2007 [cited by applicant]
US 7790449B2 · Gao et al. · 2010 [cited by applicant]
US 7883858B2 · Hood et al. · 2011 [cited by applicant]
US 9061059B2 · Chakraborty et al. · 2015 [cited by applicant]
US 9434928B2 · Mendell et al. · 2016 [cited by applicant]
US 10105453B2 · Mendell et al. · 2018 [cited by applicant]
US 11358993B2 · Rodino-Klapac et al. · 2022 [cited by applicant]
US 20010029040A1 · Toyo-Oka · 2001 [cited by applicant]
US 20030225260A1 · Snyder · 2003 [cited by applicant]
US 20060154250A1 · Morris et al. · 2006 [cited by applicant]
US 20070099251A1 · Zhang et al. · 2007 [cited by applicant]
US 20080249052A1 · Duan et al. · 2008 [cited by applicant]
US 20090054823A1 · Bridges et al. · 2009 [cited by applicant]
US 20090275107A1 · Lock et al. · 2009 [cited by applicant]
US 20090280103A1 · Flueck · 2009 [cited by applicant]
US 20100003218A1 · Duan et al. · 2010 [cited by applicant]
US 20100008979A1 · Tomatsu et al. · 2010 [cited by applicant]
US 20100026655A1 · Harley · 2010 [cited by applicant]
US 20100075866A1 · Hood et al. · 2010 [cited by applicant]
US 20100112694A1 · Marban · 2010 [cited by applicant]
US 20100120627A1 · Belouchi et al. · 2010 [cited by applicant]
US 20100247495A1 · Ichim et al. · 2010 [cited by applicant]
US 20100266551A1 · Richard et al. · 2010 [cited by applicant]
US 20110023139A1 · Weinstein et al. · 2011 [cited by applicant]
US 20110053221A1 · Chen et al. · 2011 [cited by applicant]
US 20110070210A1 · Andrijauskas · 2011 [cited by applicant]
US 20110076744A1 · Wright et al. · 2011 [cited by applicant]
US 20110082192A1 · Milne et al. · 2011 [cited by applicant]
US 20110104120A1 · Xiao et al. · 2011 [cited by applicant]
US 20110266551A1 · Thompson et al. · 2011 [cited by applicant]
US 20110294193A1 · Amalfitano et al. · 2011 [cited by applicant]
US 20110301226A1 · Mendell et al. · 2011 [cited by applicant]
US 20120087862A1 · Hood et al. · 2012 [cited by applicant]
US 20130171172A1 · Richard et al. · 2013 [cited by applicant]
US 20140010861A1 · Bancel et al. · 2014 [cited by applicant]
US 20140147432A1 · Bancel · 2014 [cited by examiner]
US 20140179770A1 · Zhang et al. · 2014 [cited by applicant]
US 20140234255A1 · Lai et al. · 2014 [cited by applicant]
US 20140249208A1 · Chakraborty et al. · 2014 [cited by applicant]
US 20140256802A1 · Boye et al. · 2014 [cited by applicant]
US 20140273231A1 · Zhang et al. · 2014 [cited by applicant]
US 20140323956A1 · Mendell et al. · 2014 [cited by applicant]
US 20150111955A1 · High et al. · 2015 [cited by applicant]
US 20150125429A1 · Perlingeiro et al. · 2015 [cited by applicant]
US 20150232883A1 · Dahlman et al. · 2015 [cited by applicant]
US 20150238627A1 · Leger et al. · 2015 [cited by applicant]
US 20160058890A1 · Buj Bello et al. · 2016 [cited by applicant]
US 20180256752A1 · Buj Bello et al. · 2018 [cited by applicant]
US 20190000998A1 · Mendell et al. · 2019 [cited by applicant]
US 20190202880A1 · Rodino-Klapac et al. · 2019 [cited by applicant]
US 20190343966A1 · Wang et al. · 2019 [cited by applicant]
US 20200339960A1 · Sahenk · 2020 [cited by applicant]
US 20210128749A1 · Rodino-Klapac et al. · 2021 [cited by applicant]
US 20210393801A1 · Rodino-Klapac et al. · 2021 [cited by applicant]
EP 0127839A2 · 1984 [cited by applicant]
EP 0155476A · 1985 [cited by applicant]
EP 2859896A1 · 2015 [cited by applicant]
JP 2006121961A · 2006 [cited by applicant]
WO WO9503392A1 · 1995 [cited by applicant]
WO WO9513365A1 · 1995 [cited by applicant]
WO WO9513392A1 · 1995 [cited by applicant]
WO WO9617947A1 · 1996 [cited by applicant]
WO WO9706243A1 · 1997 [cited by applicant]
WO WO9708298A1 · 1997 [cited by applicant]
WO WO9709441A2 · 1997 [cited by applicant]
WO WO9721825A1 · 1997 [cited by applicant]
WO WO9809657A2 · 1998 [cited by applicant]
WO WO9901176A1 · 1999 [cited by applicant]
WO WO9911764A2 · 1999 [cited by applicant]
WO WO9943360A1 · 1999 [cited by applicant]
WO WO0183692A2 · 2001 [cited by applicant]
WO WO02053703A2 · 2002 [cited by applicant]
WO WO03074714A1 · 2003 [cited by applicant]
WO WO2004058146A2 · 2004 [cited by applicant]
WO WO2007057781A2 · 2007 [cited by applicant]
WO WO2009019505A2 · 2009 [cited by applicant]
WO WO2009054725A2 · 2009 [cited by applicant]
WO WO2013016352A1 · 2013 [cited by applicant]
WO WO2013078316A1 · 2013 [cited by applicant]
WO WO2013123503A1 · 2013 [cited by applicant]
WO WO2013151665A2 · 2013 [cited by applicant]
WO WO2013176772A1 · 2013 [cited by applicant]
WO WO2014037526A1 · 2014 [cited by applicant]
WO WO2014093622A2 · 2014 [cited by applicant]
WO WO2014093712A1 · 2014 [cited by applicant]
WO WO2014204725A1 · 2014 [cited by applicant]
WO WO2015018503A1 · 2015 [cited by applicant]
WO WO2015021457A2 · 2015 [cited by applicant]
WO WO2015110449A1 · 2015 [cited by applicant]
WO WO2015158749A2 · 2015 [cited by applicant]
WO WO2015197232A1 · 2015 [cited by applicant]
WO WO2016115543A2 · 2016 [cited by applicant]
WO WO2017087395A1 · 2017 [cited by applicant]
WO WO2017165859A1 · 2017 [cited by applicant]
WO WO2017180857A1 · 2017 [cited by applicant]
WO WO2017180976A1 · 2017 [cited by applicant]
WO WO2017181014A1 · 2017 [cited by applicant]
WO WO2017181015A1 · 2017 [cited by applicant]
WO WO2017221145A1 · 2017 [cited by applicant]
WO WO2018170408A1 · 2018 [cited by applicant]
WO WO2019012336A1 · 2019 [cited by applicant]
WO WO2019078916A1 · 2019 [cited by applicant]
WO WO2019118806A1 · 2019 [cited by applicant]
WO WO2019152474A1 · 2019 [cited by applicant]
WO WO2019195362A1 · 2019 [cited by applicant]
WO WO2019209777A1 · 2019 [cited by applicant]
WO WO2019245973A1 · 2019 [cited by applicant]
WO WO2020006458A1 · 2020 [cited by applicant]
WO WO2020123645A1 · 2020 [cited by applicant]
WO WO2020176614A1 · 2020 [cited by applicant]
WO WO2021035120A1 · 2021 [cited by applicant]
WO WO2021257655A1 · 2021 [cited by applicant]
Johns Hopkins Medicine, 2023 (Types of Muscular Dystrophy and Neuromuscular diseases, p. 1-4) (Year: 2023). [cited by examiner]
NCBI, GenBank accession No. U34976.1 (Nov. 8, 1995), 2 pages. [cited by applicant]
Noguchi, S., “Human gamma-sarcoglycan mRNA, complete cds.”, Nov. 8, 1995, Database Accession No. U34976. [cited by applicant]
Herson et al., A phase I trial of adeno-associated virus serotype 1-gamma-sarcoglycan gene therapy for limb girdle muscular type 2C, Brain, 2012, vol. 135, Pt 2, pp. 483-492. [cited by applicant]
International Search Report and Written Opinion for PCT/US2019/015779 dated Apr. 30, 2019, 14 pages. [cited by applicant]
McNally et al., Mild and Severe Muscular Dystrophy Caused by a Single gamma-Sarcoglycan Mutation, American Journal of Human Genetics, Nov. 1996, vol. 59, No. 5, pp. 1040-1047. [cited by applicant]
Cordier et al., “Muscle-Specific Promoters May Be Necessary for Adeno-Associated Virus-Mediated Gene Transfer in the Treatment of Muscular Dystrophies,” Human Gene Therapy, Jan. 20, 2001, vol. 12, pp. 205-215. [cited by applicant]
Cordier et al., “Rescue of Skeletal Muscles of gamma-Sarcoglycan-Deficient Mice with Adeno-Associated Virus-Mediated Gene Transfer,” Molecular Therapy, Feb. 2000, vol. 1, No. 2 pp. 119-129. [cited by applicant]
Inouye et al., “Codon optimization of genes for efficient protein expression in mammalian cells by selection of only preferred human codons,” Protein Expression and Purification, 2015, vol. 109, pp. 47-54. [cited by applicant]
Pozsgai et al., “Systemic AAV-Mediated [beta]-Sarcoglycan Delivery Targeting Cardiac and Skeletal Muscle Ameliorates Histological and Functional Deficits in LGMD2E Mice,” Molecular Therapy, The Journal of the American S… [cited by applicant]
Pozsgai et al., “Beta-Sarcoglycan gene transfer decreases fibrosis and restores force in LGMD2E mice,” Gene Therapy, 2016, 23, pp. 57-66. [cited by applicant]
Abadi et al., Supplementation with alpha-lipoic acid, CoQ10, and vitamin E augments running performance and mitochondrial function in female mice, PLoS One, 8(4):e60722 (2013). [cited by applicant]
ABSS (Sequence Alignment; WO2020006458, SEQ ID #1; accessed Mar. 12, 2024) (Year: 2024). [cited by applicant]
ABSS2 (Sequence Alignment; U.S. Appl. No. 17/255,488, SEQ ID #1; accessed Mar. 12, 2024) (Year: 2024). [cited by applicant]
Allamand et al., Early adenovirus-mediated gene transfer effectively prevents muscular dystrophy in alpha-sarcoglycan-deficient mice, Gene Ther., 7(16):1385-91 (2000). [cited by applicant]
Anderson et al., “Nucleic acid hybridisation: A practical approach,” Ch. 4, IRL Press Limited, Oxford, England (1 page) 1985. [cited by applicant]
Anderson et al., “Quantitative Filter Hybridisation—Chapter 4”, Nucleic acid hyridisation a practical approach, 1985, pp. 73-111. [cited by applicant]
Angelini et al., The clinical spectrum of sarcoglycanopathies, Neurology, 52:176-179 (1999). [cited by applicant]
Araishi et al., Loss of the sarcoglycan complex and sarcospan leads to muscular dystrophy in beta-sarcoglycan-deficient mice, Hum. Mal. Genet. 8: 1589-1598 (1999). [cited by applicant]
Arnold et al., Electrophysiological Biomarkers in Spinal Muscular Atrophy: Preclinical Proof of Concept, Ann. Clin. Transl. Neural., 1 (1):34-44 (Jan. 2014). [cited by applicant]
Asokan et al., The AAV Vector Toolkit: Poised at the Clinical Crossroads; Molecular Therapy, 20(4):699-708 (2012). [cited by applicant]
Au et al., “Gene therapy advances: a meta-analysis of AAV Usage in Clinical Settings,” Frontiers in Medicine, Feb. 9, 2022, vol. 8 (pp. 1-14). [cited by applicant]
Bang et al., The complete gene sequence of titin, expression of an unusual approximately 700-kDa titin isoform, and its interaction with obscurin identify a novel Z-line to I-band linking system, Gire. Res. 89:1065-72 (… [cited by applicant]
Barresi et al., Disruption of heart sarcoglycan complex and severe cardiomyopathy caused by beta sarcoglycan Nmutations, J. Med. Genet. 37: 102-107 (2000). [cited by applicant]
Bartoli et al., “Safety and efficacy of AA V-mediated calpain 3 gene transfer in a mouse model of limb-girdle muscular dystrophy type 2A”, Mol. Ther., 13(2):250-259 (2006). [cited by applicant]
Bearzi et al., Human cardiac stem cells, Proc. Natl. Acad. Sci. USA. 104:14068-73 (2007). [cited by applicant]
Beastrom et al., mdx(5cv) mice manifest more severe muscle dysfunction and diaphragm force deficits than do mdx Mice, Am. J. Pathol., 179(5):2464-74 (2011). [cited by applicant]
Behlke, Chemical modification of siRNAs for in vivo use, Oligonucleotides. 18:305-319 (2008). [cited by applicant]
Belfort et al., Homing endonucleases: from genetic anomalies to programmable genomic clippers Methods Mal. Biol. 1123:1-26 (2014). [cited by applicant]
Boch et al., Breaking the code of DNA binding specificity of TAL-type III effectors, Science. 326:1509-12 (2009). [cited by applicant]
Boissel et al., “megaTALs a rare-cleaving nuclease architecture for therapeutic genome engineering,” Nucleic Acids Research, 2014, vol. 42, No. 4 (pp. 2591-2601). [cited by applicant]
Boissel et al., Assembly and characterization of megaTALs for hyperspecific genome engineering applications, Methods Mal. Biol. 1239:171-96 (2015). [cited by applicant]
Bolduc et al., “Recessive Mutations in the Putative Calcium-Activated Chloride Channel Anoctamin 5 Cause Proximal LGMD2L and Distal MMD3 Muscular Dystrophies”, The American Journal of Human Genetics, 86, Feb. 12, 2010, … [cited by applicant]
Bonnemann et al., Betasarcoglycan (A3b) mutations cause autosomal recessive muscular dystrophy with loss of the sarcoglycan complex, Nat. Genet., 11(3):266-273 (1995). [cited by applicant]
Bonnemann et al., Genomic screening for beta-sarcoglycan gene mutations: missense mutations may cause severe limb-girdle muscular dystrophy type 2E (LGMD 2E), Hum. Mol. Genet. 5:1953-1961 (1996). [cited by applicant]
Bouquet et al., Miyoshi-like distal myopathy with mutations in anoctamin 5 gene, Rev. Neural. (Paris), 168(2):135-41 (Feb. 2012). [cited by applicant]
Bramsen et al., Development of therapeutic-grade small interfering RNAs by chemical engineering, Front. Genet. 20:154 (2012). [cited by applicant]
Carter et al., “Adeno-associated virus vectors,” Current Opinions in Biotechnology, 1992, vol. 3, Issue 5, pp. 533-539. [cited by applicant]
Ceccadi et al., Homologous recombination-deficient tumors are hyper-dependent on POLQ mediated repair, Nature. 518:258-262 (2015). [cited by applicant]
Cekaite et al., Gene expression analysis in blood cells in response to unmodified and 2′-modified siRNAs reveals TLR-dependent and independent effects, J. Mal. Biol. 365:90-108 (2007). [cited by applicant]
Centner et al., Identification of muscle specific ring finger proteins as potential regulators of the titin kinase domain, J. Mal. Biol. 306:717-26 (2001). [cited by applicant]
Cermak et al ., “Efficient design and assembly of custom TALEN and other TAL effector-based constructs for DNA targeting,” Nucleic Acids Research, 2011, (pp. 1-11). [cited by applicant]
Cermak et al., Efficient design and assembly of custom TALENs using the Golden Gate platform, Methods Mal. Biol. 1239:133-59 (2015). [cited by applicant]
Ceyhan-Birsoy et al., Recessive truncating titin gene, TTN, mutations presenting as centronuclea1 myopathy, Neuroloov. 81:1205-14 (2013). [cited by applicant]
Chandrasekharan et al., Genetic defects in muscular dystrophy, Methods Enzymol. 479:291-322 (2010). [cited by applicant]
Chao et al., “Several log increase in therapeutic transgene delivery by distinct adeno-associated viral serotype vectors,” Molecular therapy: the journal of the American Society of Gene Therapy, 2000, vol. 2, Issue 6, p… [cited by applicant]
Chao et al., “Sustained and complete phenotype correction of hemophilia B mice following intramuscular injection of AAV1 serotype vectors,” Molecular therapy: the journal of the American Society of Gene Therapy, 2001, v… [cited by applicant]
Chauveau et al., A rising titan: TTN review and mutation update, Human Mutation. 35:1046-59 (2014). [cited by applicant]
Chernolovskaya et al., Chemical modification of siRNA, Curr. Opin. Mal. Ther. 12:158-67 (2010). [cited by applicant]
Chicoine et al., “Plasmapheresis eliminates the negative impact of AAV antibodies on microdystrophin gene expression following vascular delivery,” Molecular therapy: the journal of the American Society of Gene Therapy, … [cited by applicant]
Chicoine et al., “Vascular delivery of rAAVrh74.MCK.GALGT2 to the gastrocnemius muscle of the rhesus macaque stimulates the expression of dystrophin and laminin a2 surrogates”, Mol. Ther., 22:713-24 (2014). [cited by applicant]
Chiorini et al., Cloning and characterization of adeno-associated virus type 5, J. Viral., 73(2): 1309-19 (Feb. 1999). [cited by applicant]
Chiorini et al., Cloning of adeno-associated virus type 4 (AAV4) and generation of recombinant AAV4 particles, J. Viral., 71 (9):6823-33 (Sep. 1997). [cited by applicant]
Cho et al., DNA repair: Familiar ends with alternative endings, Nature. 518:174-6 (2015). [cited by applicant]
Chu et al., “SV40 DNA transfection of cells in suspension: analysis of the efficiency of transcription and translation of T-antigen”, Gene, 13, (1981) 197-202. [cited by applicant]
Clark et al., “Highly Purified Recombinant Adeno-Associated Virus Vectors Are Biologically Active and Free of Detectable Helper and Wild-Type Viruses,” Hum. Gene. Ther., 1996, vol. 10, Issue 6, pp. 1031-1039. [cited by applicant]
Clark et al., “Recombinant adeno-associated viral vectors mediate long-term transgene expression in muscle,” Human gene therapy, 1997, vol. 8, Issue 6, pp. 659-669. [cited by applicant]
Clark et al., A stable cell line carrying adenovirus-inducible rep and cap genes allows for infectivity titration of adeno-associated virus vectors, Gene. Therapy, 3(12):1124-1132 (1996). [cited by applicant]
Cox et al., “Therapeutic genome editing: prospects and challenges,” Nature Medicine, Feb. 21, 2015, vol. 2 (pp. 121-131). [cited by applicant]
Cserjesi et al., “Myogenin induces the myocyte-specific enhancer binding factor MEF-2 independently of other muscle-specific gene products,” Mol. Cell Biol., 1991, vol. 11, Issue 10, pp. 4854-4862. [cited by applicant]
D'Amario et al., Functionally competent cardiac stem cells can be isolated from endomyocardial biopsies of patients with advanced cardiomyopathies, Gire. Res. 108:857-61 (2011). [cited by applicant]
Database Genbank [online], Accession No. AJ277892.2, Nov. 14, 2006 issue. [cited by applicant]
Daya et al., “Gene Therapy Using Adeno-Associated Virus Vectors,” Clinical Microbiology Reviews, Oct. 2008, vol. 21, No. 4 (pp. 583-593). [cited by applicant]
De et al., “High levels of persistent expression of alpha1-antitrypsin mediated by the nonhuman primate serotype rh.10 adeno-associated virus despite preexisting immunity to common human adeno-associated viruses,” Molec… [cited by applicant]
Deleavey et al., Chemical modification of siRNA, Curr. Protoc. Nucleic Acid Chem. Chapter 16:Unit 16.3 (2009). [cited by applicant]
Doench et al., “Optimized sgRNA design to maximize activity and minimize off-target effects of CRISPR-Cas9”, Nature Biotechnology, Feb. 2016, vol. 34, No. 2 (pp. 184-191). [cited by applicant]
Draviam et al., The beta-li-core of sarcoglycan is essential for deposition at the plasma membrane, Muscle and Nerve. 34:691-701 (2006). [cited by applicant]
Dreier et al., “Development of Zinc Finger Domains for Recognition of the 5′-ANN-3′ Family of DNA Sequences and Their Use in the Construction of Artificial Transcription Factors,” The Journal of Biological Chemistry, Au… [cited by applicant]
Dreier et al., Insights into the molecular recognition of the 5′-GNN-3′ family of DNA sequences by zinc finger domains, J. Mal. Biol. 303:489-502 (2000). [cited by applicant]
Dreier, B. et al, “Development of zinc finger domains for recognition of the 5′-CNN-3′ family DNA sequence and their use in the construction of artificial transcription factors”, The Journal of Biological Chemistry, vol… [cited by applicant]
Dressman et al., Delivery of alpha- and beta-sarcoglycan by recombinant adeno-associated virus: efficient rescue of muscle, but differential toxicity, Hum. Gene. Ther., 13(13):1631-1646 (2002). [cited by applicant]
Dressman, AAV-Mediated gene transfer to models of muscular dystrophy: Insights into assembly of multi-subunit membrane proteins, University of Pittsburgh (1997). [cited by applicant]
Durbeej et al., Disruption of the beta-sarcoglycan gene reveals pathogenetic complexity of limb-girdle muscular dystrophy type 2E, Mol. Cell. 5:141-151 (2000). [cited by applicant]
Fanin et al., Gender difference in limb-girdle muscular dystrophy: a muscle fiber morphometric study in 101 patients, Clin. Neuropathology, 33:179-801 (2014). [cited by applicant]
Fanin et al., LGMD2E patients risk developing dilated cardiomyopathy, Neuromuscl. Disord., 13(4):303-309 (2003). [cited by applicant]
Flotte et al., “Gene expression from adeno-associated virus vectors in airway epithelial cells,” American journal of respiratory cell and molecular biology, 1992, vol. 7, Issue 3, pp. 349-356. [cited by applicant]
Fonfara et al., “Phylogeny of Cas9 determines functional exchangeability of dual-RNA and Cas9 among orthologous type II CRISPR-Cas systems”, Nucleic Acids Research, vol. 42, No. 4, Nov. 22, 2013, pp. 2377-2590 (14 pages… [cited by applicant]
Forbes et al., “Skeletal muscles of ambulant children with Duchenne muscular dystrophy: validation of multicenter study of evaluation with MR imaging and MR spectroscopy”, Radiology, 269:198-207 (2013). [cited by applicant]
Fowler, et al., Improved knockdown from artificial microRNAs in an enhanced miR-155 Backbone: a designer's guide to potent multi-target RNAi, Nucleic Acids Research, 44(5): e48, (Nov. 2015). [cited by applicant]
Foye, Whole Genome Sequencing Solved Our Family's Genetic Mystery: Titin, Narrat. Inq. Bioeth 5:206-8 (2015). [cited by applicant]
Francois, et al., Accurate Titration of Infectious AAV Particles Requires Measurement of Biologically Active Vector Genomes and Suitable Controls. Molecular Therapy—Methods & Clinical Development, Sep. 21, 2018, vol. 10… [cited by applicant]
Fucini et al., Adenosine modification may be preferred for reducing siRNA immune stimulation, Nucleic Acid Ther. 22:205-210 (2012). [cited by applicant]
Gaglione et al., Recent progress in chemically modified siRNAs, Mini. Rev. Med. Chem. 10:578-9t (2010). [cited by applicant]
Gao et al., A novel and efficient model of coronary artery ligation and myocardial infarction in the mouse, Gire. Res. 107:1445-53 (2010). [cited by applicant]
Gao et al., A novel and efficient model of coronary artery ligation in the mouse, Methods Mal. Bic 1037:299-311 (2013). [cited by applicant]
Gao et al., Adeno-associated viruses undergo substantial evolution in primates during natural infections, Proc. Natl. Acad. Sci. U.S.A., 2003, vol. 100, pp. 6081-6086. [cited by applicant]
Gao, G. et al., “Clades of Adeno-Associated Viruses Are Widely Disseminated in Human Tissues,” Journal of Virology, vol. 78, No. 12, 6381-6388, 2004. [cited by applicant]
Gautel et al., The central Z-disk region of titin is assembled from a novel repeat in variable copy numbers, Journal of Cell Science. 109:2747-2754 (1996). [cited by applicant]
Gebeyehu, et al., “Novel biotinylated nucleotide—analogs for labeling and colorimetric detection of DNA,” Nucleic Acids Research, vol. 15, No. 11, (Jun. 11, 1987), p. 4513-4534. [cited by applicant]
GenBank Accession No. AF028704.1, Adena-associated virus 6, complete genome, Jan. 12, 1998. [cited by applicant]
GenBank Accession No. AF028705.1, Adeno-associated virus 3B, complete genome, Jan. 12, 1998. [cited by applicant]
GenBank Accession No. AF085716.1, Adeno-associated virus 5 DNA binding trs helicase (Rep22) and capsid protein (VP1) aenes, complete eds, Feb. 9, 1999. [cited by applicant]
Genbank Accession No. AX753246, Sequence 1 from Patent EP1310571, Jun. 23, 2003. [cited by applicant]
GenBank Accession No. AX753249, Sequence 4 from Patent EP1310571, Jun. 23, 2003. [cited by applicant]
GenBank Accession No. AX753250.1, Sequence 5 from Patent EP1310571, Jun. 23, 2003. [cited by applicant]
GenBank Accession No. AY631965.1, Adena-associated virus 10 nonstructural protein and caps protein genes, complete eds, Nov. 30, 2004. [cited by applicant]
GenBank Accession No. AY631966.1, Adena-associated virus 11 nonstructural protein and caps protein genes, complete eds, Nov. 30, 2004. [cited by applicant]
GenBank Accession No. DO813647.1, Adena-associated virus 12 Rep78 and VP1 genes, complete eds, Feb. 20, 2008. [cited by applicant]
GenBank Accession No. EU285562.1, Adena-associated virus 13 nonstructural protein and capsid protein genes, complete eds, Sep. 23, 2008. [cited by applicant]
Genbank Accession No. NC_001401.0, Adeno-associated virus-2, complete genome, Aug. 13, 2018. [cited by applicant]
GenBank Accession No. NC_001401.2, Adeno-associated virus-2, complete genome, Aug. 13, 2018. [cited by applicant]
Genbank Accession No. NC_001729.1, Adeno-associated virus-3, complete genome, Aug. 13, 2018. [cited by applicant]
GenBank Accession No. NC_001829.1, Adeno-associated virus-4, complete genome, Aug. 13, 2018. [cited by applicant]
GenBank Accession No. NC_001862, Adeno-associated virus 6, complete genome, Jan. 12, 2004, located at <https:www.ncbi.nlm.nih.gov/nuccore/NC_001862.1?report=genbank>. [cited by applicant]
GenBank Accession No. NC_002077.1, Adeno-associated virus-1, complete genome, Aug. 13, 2018, located at <https://www.ncbi.nlm.nih.gov/nuccore/NC_002077>. [cited by applicant]
GenBank Accession No. NC_006152.1, Adeno-associated virus 5, complete genome, Aug. 13, 2018. [cited by applicant]
GenBank Accession No. NC_006260.1, Adeno-associated virus-7, complete genome, Aug. 13, 2018. [cited by applicant]
GenBank Accession No. NC_006261.1, Adeno-associated virus-8, complete genome, Aug. 13, 2018. [cited by applicant]
Genbank Accession No. NM_00232.4, [cited by applicant]
Genbank Accession No. NP 000233.1, Beta Sarcoglyan {43kD dystrophin-associated glycoprotein) [cited by applicant]
Genbank Accession No. J01901, Adeno-associated virus 2, complete genome, Apr. 27, 1993. [cited by applicant]
GenBank Accession No. U89790.1, Adeno-associated virus 4, complete genome, Aug. 21, 2017. [cited by applicant]
GenBank Registered No. NG_011618, [cited by applicant]
Genbank Synthetic construct [cited by applicant]
GenBank: Accession No. NP 000223.1: beta-sarcoglycan sequence, dated Mar. 3, 1999. [cited by applicant]
Georganopoulou et al., “A Journey with LGMD: From Protein Abnormalities to Patient Impact”, The Protein Journal, Kluwer Academic/Plenum Publishers, Dordrecht, NL, vol. 40, No. 4, Jun. 10, 2021, pp. 466-488. [cited by applicant]
Gerull et al., Identification of a novel frameshift mutation in the giant muscle filament titin in a large Australian family with dilated cardiomyopathy, J. Mal. Med. (Berl). 84:478-83 (2006). [cited by applicant]
Gerull et al., Mutations of TTN, encoding the giant muscle filament titin, cause familial dilated cardiomyopathy, Nat. Genet. 30:201-4 (2002). [cited by applicant]
Gibertini et al., Fibrosis and inflammation are greater in muscles of beta-sarcoglycan-null mouse than mdx mouse, Cell Tissue Res. 356:427-443 (2014). [cited by applicant]
Goeddel, “Gene Expression Technology: Methods in Enzymology,” Academic Press, vol. 185, Jun. 11, 1990, pp. 3-7. [cited by applicant]
Gombash et al., Adeno-Associated Viral Vector Delivery to the Enteric Nervous System: A Review, Postdoc J., 2015, vol. 3, Issue 8, pp. 1-12. [cited by applicant]
Govoni et al., “Ongoing therapeutics trials and outcome measures for Duchenne muscular dystrophy”, Cell Mol. Life Sci., 70:4585-602 (2013). [cited by applicant]
Graham et al., A new technique for the assay of infectivity of human adenovirus 5 DNA, Virology, 1973, vol. 52, Issue 2, pp. 456-467. [cited by applicant]
Gramlich et al., “Antisense-mediated exon skipping: a therapeutic strategy for titin-based dilated cardiomyopathy,” EMBO Molecular Medicine, 7(5): 562-76 (2015). [cited by applicant]
Gramlich et al., “Stress-induced dilated cardiomyopathy in a knock-in mouse model mimicking human titin-based disease”, J. Mal. Cell Cadiol. 47:352-8 (2009). [cited by applicant]
Granzier et al., “Deleting titin's I-band/A-band junction reveals critical roles for titin in biomechanica sensing and cardiac function”, Proc. Natl. Acad. Sci. USA. 111:14589-94 (2014). [cited by applicant]
Greig et al., “Impact of intravenous infusion time on AAV8 vector pharmacokinetics, safety, and liver transduction in cynomolgus macaques,” Molecular Therapy—Methods & Clinical Develop, 3: 16079, 7 pages (2016). [cited by applicant]
Grieger et al., “Production and characterization of adeno-associated viral vectors”, Nat. Protoc. 1 :1412-1428 (2006). [cited by applicant]
Griffin et al. Preclinical systemic delivery of adeno-associated [alpha]-sarcoglycan gene transfer for limb-qirdle muscular dystrophy, Human Gene Therapy, 32(7-8): 390-404, (Apr. 2021). [cited by applicant]
Griffin et al., Defective Membrane Fusion and Repair in Anoctamin5-Deficient Muscular Dystrophy, Human Molecular Genetics, vol. 25, No. 10, pp. 1900-1911 (Feb. 23, 2016). [cited by applicant]
Griffin et al., “Dose-Escalation of Systemically Delivered Adeno-Associated Virus-Mediated alpha-Sarcoglycan in a Mouse Model With Limb-Girdle Muscular Dystrophy Type 2D,” Presented at the 2019 Muscular Dystrophy Associ… [cited by applicant]
Griffin et al., “Systemic Dose Escalation Study of Alpha-Sarcoglycan Provides Functional Improvement in SGCA (I-) Mouse Model of LGMD2D,” Molecular Therapy, vol. 26, No. 5S1, May 2018, p. 166. [cited by applicant]
Grose et al., “Homologous Recombination Mediates Functional Recovery of Dysferlin Deficiency following AAV5 Gene Transfer”, PLoS One, Jun. 2012, vol. 7, Issue 6, e39233. [cited by applicant]
Guilinger et al., “Fusion of catalytically inactive Cas9 to Fokl nuclease improves the specificity of genome modification,” Nature Biotechnology, vol. 32, No. 6, Jun. 2014 (pp. 577-582). [cited by applicant]
Gutschner et al., “Genome engineering—Matching supply with demand,” Cell Cycle, 15(11): 1395-96 2016. [cited by applicant]
Hafez et al., “Homing endonucleases: DNA scissors on a mission”, Genome. 55:553-69 (2012). [cited by applicant]
Hagan, “When are mice considered old?” The Jackson Laboratory, https://www.jax.org/news-and-insights/jax-blog/2017/november/when-are-mice-considered-old# Nov. 7, 2017 (8 pages). [cited by applicant]
Hakim et al., Monitoring murine skeletal muscle function for muscle gene therapy, Methods Mal. Biol., 2011, vol. 709, pp. 75-89. [cited by applicant]
Hakim et al., The passive mechanical properties of the extensor digitorum longus muscle are compromised in 2- to 20-mo-old mdx mice, J. Appl. Physiol. 110: 1656-1663 (2011). [cited by applicant]
Handschin et al., Peroxisome proliferator-activated receptor gamma coactivator 1 coactivators, energy homeostasis, and metabolism, Endocrine reviews, 27:728-735 (2002). [cited by applicant]
Herman et al., “Truncations of titin causing dilated cardiomyopathy”, N. Engl. J. Med. 366:619-28, 2012. [cited by applicant]
Hermonat et al., Use of adeno-associaled virus as a mammalian DNA cloning vector: transduction of neomycin resistance into mammalian tissue culture cells, Proc. Nall. Acad. Sci. U.S.A., 81:6466-6470 (1984). [cited by applicant]
Herzog et al., Stable gene transfer and expression of human blood coagulation factor IX after intramuscular injection of recombinant adeno-associated virus, Proc. Natl. Acad. Sci. USA, 1997, vol. 94 (pp. 5804-5809). [cited by applicant]
Hicks et al., A founder mutation in Anoctamin 5 is a major cause of limb-girdle muscular dystrophy, Brain, 134 (Pt. 1):171-82 (Jan. 2011). [cited by applicant]
Horii et al., Validation of microinjection methods for generating knockout mice by CRISPR/Cas-mediated genome engineering, Sci Rep. 4:4513 (2014). [cited by applicant]
International Application No. PCT/US2017/027636, International Preliminary Report on Patentability, mailed Oct. 16, 2018 (5 pages). [cited by applicant]
International Application No. PCT/US2017/027636, International Search Report and Written Opinion, mailed Jul. 5, 2017 (8 Pages). [cited by applicant]
International Application No. PCT/US19/39893, International Search Report and Written Opinion, mailed Sep. 25, 2019. [cited by applicant]
International Application No. PCT/US20/47339, International Preliminary Report on Patentability, mailed Mar. 3, 2022. [cited by applicant]
International Application No. PCT/US2016/061703, International Preliminary Report on Patentability, mailed May 15, 2018. [cited by applicant]
International Application No. PCT/US2020/019892, International Preliminary Report on Patentability, mailed Sep. 10, 2021 (8 pages). [cited by applicant]
International Preliminary Report on Patentability for Appl. Ser. No. PCT/US2016/062052 dated May 22, 2018. [cited by applicant]
International Preliminary Report on Patentability for Appl. Ser. No. PCT/US2017/027583 dated Oct. 25, 2018. [cited by applicant]
International Preliminary Report on Patentability for Appl. Ser. No. PCT/US2019/039893 dated Dec. 29, 2020 (7 pages). [cited by applicant]
International Preliminary Report on Patentability on PCT Appl. No. PCT/US2012/066265 dated May 27, 2014 (9 pages). [cited by applicant]
International Search report and Written Opinion for Appl. Ser. No. PCT/US2017/027583 dated Jul. 14, 2017 (8 pages). [cited by applicant]
International Search Report and Written Opinion for Appl. Ser. No. PCTUS2016/061703 dated Feb. 2, 2017 (13 pages). [cited by applicant]
International Search Report and Written Opinion on PCT Appl. No. PCT/US2020/047339 dated Dec. 10, 2020 (12 pages). [cited by applicant]
International Search Report and Written Opinion on PCT Appl. No. PCT/US2012/066265 dated Mar. 28, 2013 (7 pages). [cited by applicant]
International Search Report for Appl. Ser. No. PCT/US2016/062052 dated Feb. 7, 2017 (5 pages). [cited by applicant]
International Search Report issued in connection with PCT/US2020/019892 dated May 14, 2020 (4 pages). [cited by applicant]
Itoh-Satoh et al., Titan mutations as the molecular basis for dilated cardiomyopathy, Biochem. Biophys. Res. Commun. 291:385-93 (2002). [cited by applicant]
Jaber et al., Titin isoforms, extracellular matrix, and global chamber remodeling in experimental dilated cardiomyopathy: functional implications and mechanistic insight, Circ. Heart Fail. 1:192-9 (2008). [cited by applicant]
Jinek et al., “A Programmable Dual-RNA-Guided DNA Endonuclease in Adaptive Bacterial Immunity,” Science, Aug. 17, 2012, 337(6096):816-821. [cited by applicant]
Johnson et al., “Muscle creatine kinase sequence elements regulating skeletal and cardiac muscle expression in transgenic mice,” Mol. Cell Biol., 1989, vol. 9, Issue 8, pp. 3393-3399. [cited by applicant]
Judge et al., “Design of noninflammatory synthetic siRNA mediating potent gene silencing in vivo”, Mol. Ther. 13:494-505 (2006). [cited by applicant]
Justison et al., Percutaneous assisted venous return isolated limb perfusion, J. Extra Corpor. Technol., 2009, vol. 41, Issue 4, pp. 231-234. [cited by applicant]
Kajigaya et al., Self-assembled B19 parvovirus caps ids, produced in a baculovirus system, are antigenically and immunogenically similar to native virions, Proc. Natl. Acad. Sci. USA, 88(11):4646-50 (Jun. 1991). [cited by applicant]
Kariko et al., “Suppression of RNA recognition by Toll-like receptors: the impact of nucleoside modification and the evolutionary origin of RNA,” Immunity, Aug. 2005, vol. 23 (pp. 165-175). [cited by applicant]
Kennell, “Principles and Practices of Nucleic Acid Hybridization,” Progress in Nucleic Acid Research and Molecular Biology, Academic Press, vol. 11, 1971, (pp. 259-301). [cited by applicant]
Kent et al., “Mechanism of microhomology-mediated end-joining promoted by human DNA polymerase theta”, Nat. Struct. Mol. Biol. 22:230-237 (2015). [cited by applicant]
Kessler et al., “Gene delivery to skeletal muscle results in sustained expression and systemic delivery of a therapeutic protein,” PNAS, 1996, vol. 93, pp. 14082-14087. [cited by applicant]
Kirnbauer et al., Virus-like particles of bovine papillomavirus type 4 in prophylactic and therapeutic immunization, Virology, 219(1):37-44 (May 1996). [cited by applicant]
Kleinstiver et al., The I-Tevl nuclease and linker domains contribute to the specificity of monomerh TALENs, G3 (Bethesda). 4:1155-65 (2014). [cited by applicant]
Kobayashi et al., Sarcolemma-localized nNOS is required to maintain activity after mild exercise, Nature. 456:511-5 (2008). [cited by applicant]
Kole et al., “RNA therapeutics: beyond RNA interference and antisense oligonucleotides”, Nat Rev Drug Discov. Jan. 20, 2012;11(2):125-40. doi: 10.1038/nrd3625. [cited by applicant]
Kolmerer et al., “Genomic organization of M line titin and its tissue-specific expression in two distinct isoforms”, J. Mol. Biol. 256:556-63 (1996). [cited by applicant]
Kormann et al., “Expression of therapeutic proteins after delivery of chemically modified mRNA in mice,” Nature Biotechnology, Feb. 2011, vol. 29, No. 2 (pp. 154-157). [cited by applicant]
Kornberg et al., “The early history of DNA polymerase: a commentary by Arthur Kornberg”, Biochimica et Biophysica Acta. 1000:53-56 (1989). [cited by applicant]
Kotin et al., “Manufacturing Clinical Grade Recombinant Adeno-Associated Virus Using Invertebrate Cell Lines,” Human Gene Therapy, 28(4):Abstract Only, (Apr. 1, 2017). [cited by applicant]
Kotin et al., Manufacturing Clinical Grade Recombinant Adeno-Associated Virus Using Invertebrate Cell Lines, Hum. Gene Ther., 28(4):350-360 (2017). [cited by applicant]
Kramerova et al., “Null mutation of calpain 3 {p94) in mice causes abnormal sarcomere formation in vivo and in vitro”, Hum. Mol. Genet., 13(13):1373-1388 (2004). [cited by applicant]
Kramerova et al., Failure to up-regulate transcription of genes necessary for muscle adaptation underlies limb girdle muscular dystrophy 2A calpainopathy, Hum. Mol. Genet., 25(11):2194-2207 (2016). [cited by applicant]
Labeit et al., “Titins: giant proteins in charge of muscle ultrastructure and elasticity”, Science. 270:293-6 (1995). [cited by applicant]
Laughlin et al., “Cloning of infectious adeno-associaled virus genomes in bacterial plasmids,” Gene, 1983, vol. 23, Issue 1, pp. 65-73. [cited by applicant]
Laws et al., Progression of kyphosis in mdx mice, J. Appl. Physiol. 97:1970-7 (2004). [cited by applicant]
Lebkowski et al., Adeno-associated virus: a vector system for efficient introduction and integration of DNA into a variety of mammalian cell types, Mal. Cell. Biol., 1988, vol. 8, Issue 10, pp. 3988-3996. [cited by applicant]
Lewinter et al., Cardiac titin and heart disease, J. Cardiovasc. Pharmacol. 63:207-12 (2014). [cited by applicant]
Lewinter, “Titin isoforms in heart failure: are there benefits to supersizing”, Circulation. 110:109-11 2004. [cited by applicant]
Lewis et al., “Generation of neutralizing activity against human immunodeficiency virus type 1 in serum by antibody gene transfer,” Journal of virology, 2002, vol. 76, Issue 17, pp. 8769-8775. [cited by applicant]
Li et al., “Modularly assembled designer TAL effector nucleases for targeted gene knockout and gene replacement in eukaryotes,” Nucleic Acids Research, 2011, vol. 39, No. 14 (pp. 6315-6325). [cited by applicant]
Li et al., Electrical impedance myography for the in vivo and ex vivo assessment of muscular dystrophy (mdx) mouse muscle, Muscle Nerve, 49(6):829-35 (Jun. 2014). [cited by applicant]
Li et al., Electrophysiologic biomarkers for assessing disease progression and the effect of riluzole in SOD1 G93A ALS mice, PLoS One, 8(6):e65976 (Jun. 2013). [cited by applicant]
Li et al., Intracoronary administration of cardiac stem cells in mice: a new, improved technique for cell therapy in murine models, Basic Res. Cardiol. 106:849-64 (2011). [cited by applicant]
Lin et al., Transcriptional co-activator PGC-1 alpha drives the formation of slow-twitch muscle fibres, Nature, 418:797-801 (2002). [cited by applicant]
Liu et al., “Adeno-associated virus-mediated microdystrophin expression protects young mdx muscle from contraction-induced injury,” Molecular therapy: the journal of the American Society of Gene Therapy, 2005, vol. 11, … [cited by applicant]
Liu et al., “Validated Zinc Finger Protein Designs for All 16 GNN DNA Triplet Targets,” The Journal of Biological Chemistry, Feb. 8, 2002, vol. 277, No. 6 (pp. 3850-3856). [cited by applicant]
Louis et al., “EM_EST:BE676391”, Jan. 27, 2011 (Jan. 27, 2011), XP055708767, Retrieved from the Internet: URL:http://ibis.internal.epo.org/exam/dbfetch.jsp?id=EM_EST:BE676391 [retrieved on Jun. 25, 2020]. [cited by applicant]
Ma et al., Pol III Promoters to express small RNAs: Delineation of transcription initiation, Mol. Ther. Nucleic Acids. 3:e161 (2014). [cited by applicant]
Mader et al., “A steroid-inducible promoter for the controlled overexpression of cloned genes in eukaryotic cells,” Proc Natl. Acad. Sci. U.S.A., 1993, vol. 90, Issue 12, pp. 5603-5607. [cited by applicant]
Mahmood et al., “Limb-girdle muscular dystrophies: Where next after six decades from the first proposal (review),” Molecular Medicine reports, 2014, vol. 9 (pp. 1515-1532). [cited by applicant]
Mak et al., “The crystal structure of TAL effector PthXo1 bound to its DNA target,” Science, Feb. 10, 2012, vol. 335, No. 6069 (pp. 716-719). [cited by applicant]
Makarenko et al., Passive stiffness changes caused by upregulation of compliant titin isoforms in human dilated cardiomyopathy hearts, Gire. Res. 95:708-16 (2004). [cited by applicant]
Marsic et al., Vector Design Tour de Force: Integrating Combinatorial and Rational Approaches to Derive Novel Adeno-associated Virus Variants, Molecular Therapy, 22(11):1900-1909 (2014). [cited by applicant]
Martin et al., Overexpression of Galgt2 in skeletal muscle prevents injury resulting from eccentric contractions in both mdx and wild-type mice, Am. J. Physiol. Cell Physiol., vol. 296, pp. 476-488, Dec. 24, 2008. [cited by applicant]
Mashiko et al., Generation of mutant mice by pronuclear injection of circular plasmid expressing Cas9 and single guided RNA, Sci. Rep. 3:3355 (2013). [cited by applicant]
Mateos-Gomez et al., Mammalian Polymerase theta promotes alternative-NHEJ amd suppresses recombination, Nature. 518:254-257 (2015). [cited by applicant]
Matsuda et al., Visualization of dystrophic muscle fibers in mdx mouse by vital staining with Evans blue: evidence of apoptosis in dystrophin-deficient muscle, J. Biochem., 118(5):959-964 (1995). [cited by applicant]
McCarty et al., “Adeno-associated virus terminal repeat (TR) mutant generates self-complementary vectors to overcome the rate-limiting step to transduction in vivo”, Gene Therapy, vol. 10, May 30, 2003, pp. 2112-2118. [cited by applicant]
McCarty et al., “Self-complementary recombinant adeno-associated virus (scAAV) vectors promote efficient transduction independently of DNA synthesis”, Gene Therapy, May 22, 2001, vol. 8, pp. 1248-1254. [cited by applicant]
McCarty et al., Self-complementary AAV Vectors; Advances and Applications, Molecular Therapy, 2008, vol. 16, Issue 10, pp. 1648-1656. [cited by applicant]
McLaughlin et al., “Adeno-Associated Virus General Transduction Vectors: Analysis of Proviral Structures”, Journal of Virology, 1988, vol. 62, No. 6, pp. 1963-1973. [cited by applicant]
McNally et al., The genetic landscape of cardiomyopathy and its role in heart failure, Cell. Metab. 21:174-182 (2015). [cited by applicant]
Meadows et al., Micro-RNA-29 Overexpression by adeno-associated virus suppresses fibrosis in mdx:utm+/− Mice (S61.003), Neurology, 82:S61.003 (Abstract) (2014). [cited by applicant]
Meadows et al., Reducing Skeletal Muscle Fibrosis with AAV-Delivered miR-29, 2012, Neurology, vol. 78, Issue 1, Supplement PO4.089. [cited by applicant]
Melacini et al., Heart involvement in muscular dystrophies due to sarcoglycan gene mutations, Muscle Nerve. 22:473-479 (1999). [cited by applicant]
Mendell et al., “A phase 1/2a follistatin gene therapy trial for becker muscular dystrophy,” Molecular therapy : the journal of the American Society of Gene Therapy, 2015, vol. 23, Issue 1, pp. 192-201. [cited by applicant]
Mendell et al., “Gene Therapy for Muscular Dystrophy: Lessons Learned and Path Forward”, Neuroscience Letters, vol. 527, No. 2, Oct. 2012, 21 pages. [cited by applicant]
Mendell et al., “Limb-girdle muscular dystrophy type 2D gene therapy restores alpha-sarcoglycan and associated proteins,” Ann. Neural., 2009, vol. 66 Issue 3, pp. 290-297. [cited by applicant]
Mendell et al., “Sustained alpha-sarcoglycan gene expression after gene transfer in limb-girdle muscular dystrophy, type 2D,” Annals of neurology, 2010, vol. 68, Issue 5, pp. 629-638. [cited by applicant]
Mendell et al., Gene Delivery for Limb-Girdle Muscular Dystrophy Type 2D by Isolated Limb Infusion, Human Gene Therapy, 2019, vol. 30, Issue 7, pp. 794-801. [cited by applicant]
Mendell et al., Gene Therapy for Spinal Muscular Atrophy Type 1 Shows Potential to Improve Survival and Motor Functional Outcomes, Mol. Ther. 24:S190 (2016). [cited by applicant]
Mendell et al., Single-Dose Gene-Replacement Therapy for Spinal Muscular Atrophy, N. Engl. J. Med., 377:1713-1722 (2017). [cited by applicant]
Merten, O.W., AAV vector production: state of the art developments and remaining challenges. Cell and Gene Therapy Insights, Dec. 1, 2016, vol. 2, No. 5, pp. 521-551. [cited by applicant]
Mingozzi et al. “Therapeutic in vivo gene transfer for genetic disease using AAV: progress and challenges”, Nature Reviews Genetics, May 2011, vol. 12 (pp. 341-355). [cited by applicant]
Monjaret et al., “The Phenotype of Dysferlin-Deficient Mice is not Rescued by Adeno-Associated Virus-Medicated Transfer of Anoctamin 5,” Human Gene Therapy Clinical Development, 24(2):65-76 (Jun. 1, 2013). [cited by applicant]
Moore et al., Limb-girdle muscular dystrophy in the United States, J. Neuropathol. Exp. Neural., 65(10):995-1003 (2006). [cited by applicant]
Moorwood et al., Isometric and eccentric force generation assessment of skeletal muscles isolated from murine models of muscular dystrophies, Journal of Visualized Experiments. 71:e50036 (2013). [cited by applicant]
Mori et al., “Two novel adeno-associated viruses from cynomolgus monkey: pseudotyping characterization of capsid protein,” Virology, 2004, vol. 330, Issue 2, pp. 375-383. [cited by applicant]
Moscou et al., “A Simple Cipher Governs DNA Recognition by TAL Effectors”, Science, Dec. 11, 2009, vol. 326 (p. 1501). [cited by applicant]
Murphy et al., “Long-term correction of obesity and diabetes in genetically obese mice by a single intramuscular injection of recombinant adeno-associated virus encoding mouse leptin,” Proceedings of the National Academ… [cited by applicant]
Muscat et al., “Multiple 5′-flanking regions of the human alpha-skeletal actin gene synergislically modulate muscle-specific expression,” Mol. Cell. Biol., 1987, vol. 7, Issue 11, pp. 4089-4099. [cited by applicant]
Muzyczka, “Use of Adeno-Associated Virus as a General Transduction Vector for Mammalian Cells,” Current Topics in Microbiology and Immunology, 1992, vol. 158, pp. 97-129. [cited by applicant]
Narayanaswami et al., Evidence-based guideline summary: diagnosis and treatment of limb-girdle and distal dystrophies: report of the guideline development subcommittee of the American Academy of Neurology and the practi… [cited by applicant]
NCBI Accession No. NG_051363.1, [cited by applicant]
NCBI Accession No. XM_012650762.1, Predicted:Propithecus coquereli titin (TTN), mRNA, dated Jun. 1, 2015. [cited by applicant]
NCBI Accession No. XM_024453100.1, Predicted: [cited by applicant]
NCBI Blast Tool: Pairwise Similarity 1, Instant App ('488) SEQ ID No. 1 [1-3977]:: U.S. Pat. No. 9,981,049 B2 SEQ ID No. 8 (CAPN3) (2024). [cited by applicant]
NCBI Blast Tool: Pairwise Similarity 2, Instant App ('488) SEQ ID No. 1 [1107-3572]:: U.S. Pat. No. 9,981,049 B2 SEQ ID No. 8 (CAPN3) (2024). [cited by applicant]
NCBI Reference Sequence: “anoctamin-5 isoform a [ [cited by applicant]
Obermann et al., Molecular structure of the sarcomeric M band: mapping of titin and myosin binding domains in myomesin and the identification of a potential regulatory phosphorylation site in myomesin, EMBO J. 16:211-20… [cited by applicant]
Pacak et al., Long-term Skeletal Muscle Protection After Gene Transfer in a Mouse Model of LGMD-2D, Molecular Therapy, 2007, vol. 15, Issue 10, pp. 1775-1781. [cited by applicant]
Paul et al., “Increased Viral Titer Through Concentration of Viral Harvests from Retroviral Packaging Lines,” Human Gene Therapy, 1993, vol. 4, Issue 5, pp. 609-615. [cited by applicant]
Pavlovicova et al., Structure and composition of tubular aggregates of skeletal muscle fibres, Gen. Physiol. Biophys., 22(4):425-40 (Dec. 2003). [cited by applicant]
Payne et al., Nutritional therapy improves function and complements corticosteroid intervention in mdx mice. Muscle Nerve. Jan. 2006; 33(1):66-77. [cited by applicant]
Peer et al., Special delivery: targeted therapy with small RNAs, Gene. Ther. 18:1127-33 (2011). [cited by applicant]
Peled et al., Titin mutation in familial restrictive cardiomyopathy, Int. J. Cardiol. 171:24-30 (2014). [cited by applicant]
Penttila et al., Eight new mutations and the expanding phenotype variability in muscular dystrophy caused by ANOS, Neurology, 78(12):897-903 (Mar. 2012). [cited by applicant]
Perrin et al., “An experimental rabies vaccine produced with a new BHK-21 suspension cell culture process: use of serum-free medium and perfusion-reactor system,” Vaccine, 1995, vol. 13, Issue 13, pp. 1244-1250. [cited by applicant]
Powers et al., Exercise-induced oxidative stress in humans: cause and consequences, Free Radic. Biol. Med., 51 (5):942-50 (Sep. 2011 ). [cited by applicant]
Pozsgai et al., “Beta-Sarcoglycan Gene Transfer Leads to Functional Improvement in a Model of LGMD2E,” Molecular Therapy vol. 22, Supplement 1, May 2014 (p. S199). [cited by applicant]
Pozsgai et al., “Pre-Clinical Efficacy Study of Beta-Sarcoglycan Gene Transfer,” Molecular Therapy, May 1, 2013, vol. 21, No. 1 (p. S68). [cited by applicant]
Rabinowitz et al., Cross-packaging of a single adeno-associated virus (AAV) type 2 vector genome into multiple AAV serotypes enables transduction with broad specificity, J Virol., 2002, vol. 76, Issue 2, pp. 791-801. [cited by applicant]
Rafael-Fortney et al., Early treatment with lisinopril and spironolactone preserves cardiac and skeletal muscle in duchenne muscular dystrophy mice, Circulation. 124:582-8 (2011). [cited by applicant]
Raj et al, “Self-complementary adeno-associated viral vectors for gene therapy of hemophilia B: progress and challenges” Expert Review of Hematology, Oct. 2011, vol. 4, No. 5 (pp. 539-549). [cited by applicant]
Ran et al., “In vivo genome editing using [cited by applicant]
Richard et al., “Mutations In The Proteolytic Enzyme Calpain 3 Cause Limb-Girdle Muscular Dystrophy Type 2A”, Cell, 81(1):27-40 (1995). [cited by applicant]
Roberts et al., Integrated allelic, transcriptional, and phenomic dissection of the cardiac effects of titin truncations in health and disease, Sci. Transl. Med. 7:270ra6 (2015). [cited by applicant]
Rodino-Klapac et al., “A translational approach for limb vascular delivery of the micro-dystrophin gene without high volume or high pressure for treatment of Duchenne muscular dystrophy,” Journal of Translational Medici… [cited by applicant]
Rodino-Klapac et al., “Micro-dystrophin and follistatin co-delivery restores muscle function in aged DMD model,” Human Molecular Genetics, Dec. 2013, vol. 22, No. 24 (pp. 4929-4937). [cited by applicant]
Rodino-Klapac et al., “Persistent expression of FLAG-tagged micro dystrophin in nonhuman primates following intramuscular and vascular delivery,” Molecular therapy: the journal of the American Society of Gene Therapy, 2… [cited by applicant]
Rodino-Klapac et al., Demonstration of SGCA Expression and Related Outcomes in Phase I/IIa Safety Isolated Limb Perfusion Trial in LGMD2D Subjects, Molecular Therapy, 2018, vol. 26, Issue 5, Supplemental 1, p. 1, Abstra… [cited by applicant]
Rodino-Klapac et al., Lack of toxicity of alpha-sarcoglycan overexpression supports clinical gene transfer trial in LGMD2D, Neurology, 2008, vol. 71, Issue 4, pp. 240-247. [cited by applicant]
Rose, comprehensive Virology 3:1-61 (1974). [cited by applicant]
Roudaut et al., “Restriction of Calpain3 Expression to the Skeletal Muscle Prevents Cardiac Toxicity and Corrects Pathology in a Murine Model of Limb-Girdle Muscular Dystrophy”, Circulation, 128(10): 1094-1104, (Sep. 20… [cited by applicant]
Ruffing et al., “Mutations in the carboxy terminus of adeno-associated virus 2 capsid proteins affect viral infectivity: lack of an RGD integrin-binding motif,” Journal of General Virology, 1994, vol. 75, pp. 3385-3392. [cited by applicant]
Rutledge et al., Infectious clones and vectors derived from adeno-associated virus (AAV) serotypes other than AAV type 2, J. Viral., 7291):309-19 (Jan. 1998). [cited by applicant]
Sahenk et al., Systemic delivery of AAVrh74.tMCK.hCAPN3 rescues the phenotype in a mouse model for LGMD2A/R1, Mol. Ther. Methods Clin. Dev., 22:401-414 (2021). [cited by applicant]
Salva et al., “Design of Tissue-specific Regulatory Cassettes for High-level rAAV-mediated Expression in Skeletal and Cardiac Muscle,” Mol. Ther., 2007, vol. 15, Issue 2, pp. 320-329. [cited by applicant]
Sambrook et al., “Molecular Cloning, a Laboratory Manual”, Cold Spring Harbor Laboratory Press, Cold Spring Harbor, N.Y., 1989, 30 pages. [cited by applicant]
Sambrook et al., Cold spring harbor laboratory press, cold Spring Harbor, N.Y., (2001). [cited by applicant]
Sambrook et al., Molecular Cloning: A Laboratory Manual, 2″ edition (1989). [cited by applicant]
Samulski et al., “Cloning of adeno-associaled virus into pBR322: rescue of intact virus from the recombinant plasmid in human cells,” Proc. Nall. Acad. Sci. U.S.A., 1982, vol. 79, Issue 6, pp. 2077-2081. [cited by applicant]
Samulski et al., “Helper-Free Stocks of Recombinant Adeno-Associated Viruses: Normal Integration Does Not Require Viral Gene Expression,” Journal of Virology, 1989, vol. 63, Issue 9, pp. 3822-3828. [cited by applicant]
Sander et al., CRISPR-Cas systems for editing, regulating and targeting genomes, Nat. Biotechnol. 32:347-55 (2014). [cited by applicant]
Sandona et al., Sarcoglycanopalhies: molecular pathogenesis and therapeutic prospects, Exp Rev. Mol. Med. 11:e28 (2009). [cited by applicant]
Sanganalmath et al., Cell therapy for heart failure: a comprehensive overview of experimental and clincal studes, current challenges, and future directions, Gire. Res. 113:810-34 (2013). [cited by applicant]