Systemic Delivery of Dysferlin Overlap Vectors Provides Long-Term Gene Expression and Functional Improvement for Dysferlinopathy

Human Gene Therapy

Volumn 29, Issue 7, 2018, Pages 749-762

  Potter, Rachael A ^a   Griffin, Danielle A ^a   Sondergaard, Patricia C ^a   Johnson, Ryan W ^a   Pozsgai, Eric R ^a,b,c   Heller, Kristin N ^a   Peterson, Ellyn L ^a   Lehtimäki, Kimmo K ^e   Windish, Hillarie P ^d   Mittal, Plavi J ^d   Albrecht, Douglas E ^d   Mendell, Jerry R ^a,b   Rodino Klapac, Louise R ^a,b,c  

^a THE RESEARCH INSTITUTE AT NATIONWIDE CHILDREN S HOSPITAL   (United States)

^b OHIO STATE UNIVERSITY   (United States)

^c THE OHIO STATE UNIVERSITY COLLEGE OF MEDICINE   (United States)

^d Jain Foundation Inc   (United States)

^e Charles River Discovery Research Services   (Finland)

Author keywords

AAV; dysferlin; gene therapy; LGMD2B; systemic delivery

Indexed keywords

ADENO ASSOCIATED VIRUS VECTOR; COLLAGEN; COMPLEMENTARY DNA; DYSFERLIN; FAT; PLACEBO; DYSF PROTEIN, MOUSE;

ANIMAL CELL; ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; ARTICLE; CELL MEMBRANE; CONTROLLED STUDY; DRUG EFFECT; DRUG EFFICACY; DRUG SAFETY; DYSFERLINOPATHY; GENE DELIVERY SYSTEM; GENE EXPRESSION; GENE THERAPY; GLUTEUS MUSCLE; IMMUNOFLUORESCENCE; IMMUNOHISTOCHEMISTRY; LIPID STORAGE; MALE; MOUSE; NONHUMAN; NUCLEAR MAGNETIC RESONANCE IMAGING; NUCLEAR MAGNETIC RESONANCE SPECTROSCOPY; VASCULARIZATION; WESTERN BLOTTING; ANIMAL; DEPENDOPARVOVIRUS; DISEASE MODEL; DRUG THERAPY; GENE EXPRESSION REGULATION; GENE VECTOR; GENETICS; HUMAN; LIMB GIRDLE MUSCULAR DYSTROPHY; MUTATION; PATHOLOGY; SKELETAL MUSCLE;

ANIMALS; DEPENDOVIRUS; DISEASE MODELS, ANIMAL; DNA, COMPLEMENTARY; DYSFERLIN; GENE EXPRESSION REGULATION; GENETIC THERAPY; GENETIC VECTORS; HUMANS; MALE; MICE; MUSCLE, SKELETAL; MUSCULAR DYSTROPHIES, LIMB-GIRDLE; MUTATION;

EID: 85050397908     PISSN: 10430342     EISSN: 15577422     Source Type: Journal    
DOI: 10.1089/hum.2017.062     Document Type: Article

References (48)

1. Bansal D, Miyake K, Vogel SS, et al. Defective membrane repair in dysferlin-deficient muscular dystrophy. Nature 2003;423:168-172.
2. Moore SA, Shilling CJ, Westra S, et al. Limb-girdle muscular dystrophy in the United States. J Neuropathol Exp Neurol 2006;65:995-1003.
3. Rosales XQ, Gastier-Foster JM, Lewis S, et al. Novel diagnostic features of dysferlinopathies. Muscle Nerve 2010;42:14-21.
4. Rosales XQ, Moser SJ, Tran T, et al. Cardiovascular magnetic resonance of cardiomyopathy in limb girdle muscular dystrophy 2B and 2I. J Cardiovasc Magn Reson 2011;13:39.
5. Emmerling VV, Fischer S, Stiefel F, et al. Temperature-sensitive miR-483 is a conserved regulator of recombinant protein and viral vector production in mammalian cells. Biotechnol Bioeng 2016;113:830-841.
6. Aoki M, Liu J, Richard I, et al. Genomic organization of the dysferlin gene and novel mutations in Miyoshi myopathy. Neurology 2001;57:271-278.
7. Liu J, Aoki M, Illa I, et al. Dysferlin, a novel skeletal muscle gene, is mutated in Miyoshi myopathy and limb girdle muscular dystrophy. Nat Genet 1998;20:31-36.
8. Liu J, Wu C, Bossie K, et al. Generation of a 3-Mb PAC contig spanning the Miyoshi myopathy/limbgirdle muscular dystrophy (MM/LGMD2B) locus on chromosome 2p13. Genomics 1998;49:23-29.
9. Grose WE, Clark KR, Griffin D, et al. Homologous recombination mediates functional recovery of dysferlin deficiency following AAV5 gene transfer. PLoS One 2012;7:e39233.
10. Lennon NJ, Kho A, Bacskai BJ, et al. Dysferlin interacts with annexins A1 and A2 and mediates sarcolemmal wound-healing. J Biol Chem 2003; 278:50466-50473.
11. Sondergaard PC, Griffin D, Pozsgai E, et al. AAV.dysferlin overlap vectors restore function in dysferlinopathy animal models. Ann Clin Transl Neurol 2015;2:256-270.
12. Kerr J, Ward C, Bloch R. Dysferlin at transverse tubules regulates Ca2+ homeostasis in skeletal muscle. Front Physiol 2014;5.
13. Lek A, Evesson F, Sutton B, et al. Ferlins: regulators of vesicle fusion for auditory neurotransmission, receptor trafficking and membrane repair. Traffic 2012;13:185-194.
14. Oulhen N, Onorato T, Ramos I, et al. Dysferlin is essential for endocytosis in the sea star oocyte. Dev Biol 2014;388:94-102.
15. Chiu YH, Hornsey MA, Klinge L, et al. Attenuated muscle regeneration is a key factor in dysferlindeficient muscular dystrophy. Hum Mol Genet 2009; 18:1976-1989.
16. de Morree A, Flix B, Bagaric I, et al. Dysferlin regulates cell adhesion in human monocytes. J Biol Chem 2013;288:14147-14157.
17. Mariano A, Henning A, Han R. Dysferlin-deficient muscular dystrophy and innate immune activation. FEBS J 2013;280:4165-4176.
18. Millay DP, Maillet M, Roche JA, et al. Genetic manipulation of dysferlin expression in skeletal muscle: novel insights into muscular dystrophy. Am J Pathol 2009;175:1817-1823.
19. Lostal W, Bartoli M, Roudaut C, et al. Lack of correlation between outcomes of membrane repair assay and correction of dystrophic changes in experimental therapeutic strategy in dysferlinopathy. PLoS One 2012;7:e38036.
20. Walter MC, Reilich P, Thiele S, et al. Treatment of dysferlinopathy with deflazacort: a double-blind, placebo-controlled clinical trial. Orphanet J Rare Dis 2013;8:26.
21. Gallardo E, Rojas-Garcia R, de Luna N, et al. Inflammation in dysferlin myopathy: immunohistochemical characterization of 13 patients. Neurology 2001;57:2136-2138.
22. Fanin M, Angelini C. Muscle pathology in dysferlin deficiency. Neuropathol Appl Neurobiol 2002;28: 461-470.
23. Barthelemy F, Wein N, Krahn M, et al. Translational research and therapeutic perspectives in dysferlinopathies. Mol Med 2011;17:875-882.
24. He B, Tang RH, Weisleder N, et al. Enhancing muscle membrane repair by gene delivery of MG53 ameliorates muscular dystrophy and heart failure in delta-Sarcoglycan-deficient hamsters. Mol Ther 2012;20:727-735.
25. Krahn M, Wein N, Bartoli M, et al. A naturally occurring human minidysferlin protein repairs sarcolemmal lesions in a mouse model of dysferlinopathy. Sci Transl Med 2010;2:50ra69.
26. Lostal W, Bartoli M, Bourg N, et al. Efficient recovery of dysferlin deficiency by dual adenoassociated vector-mediated gene transfer. Hum Mol Genet 2010;19:1897-1907.
27. Hofhuis J, Bersch K, Bussenschutt R, et al. Dysferlin mediates membrane tubulation and links Ttubule biogenesis to muscular dystrophy. J Cell Sci 2017;130:841-852.
28. Chicoine LG, Rodino-Klapac LR, Shao G, et al. Vascular delivery of rAAVrh74.MCK.GALGT2 to the gastrocnemius muscle of the rhesus macaque stimulates the expression of dystrophin and laminin alpha2 surrogates. Mol Ther 2014;22:713-724.
29. Gao G, Vandenberghe LH, Wilson JM. New recombinant serotypes of AAV vectors. Curr Gene Ther 2005;5:285-297.
30. Heller KN, Montgomery CL, Janssen PM, et al. AAV-mediated overexpression of human alpha7 integrin leads to histological and functional improvement in dystrophic mice. Mol Ther 2013;21: 520-525.
31. Sahenk Z, Galloway G, Clark KR, et al. AAV1.NT-3 gene therapy for Charcot-Marie-Tooth neuropathy. Mol Ther 2014;22:511-521.
32. Grieger JC, Soltys SM, Samulski RJ. Production of recombinant adeno-associated virus vectors using suspension HEK293 cells and continuous harvest of vector from the culture media for GMP FIX and FLT1 clinical vector. Mol Ther 2016;24:287-297.
33. Emmerling VV, Pegel A, Milian EG, et al. Rational plasmid design and bioprocess optimization to enhance recombinant adeno-associated virus (AAV) productivity in mammalian cells. Biotechnol J 2016;11:290-297.
34. Qu W, Wang M, Wu Y, et al. Scalable downstream strategies for purification of recombinant adeno-associated virus vectors in light of the properties. Curr Pharm Biotechnol 2015;16:684-695.
35. Foust KD, Wang X, McGovern VL, et al. Rescue of the spinal muscular atrophy phenotype in a mouse model by early postnatal delivery of SMN. Nat Biotechnol 2010;28:271-274.
36. Wang D, Zhong L, Nahid MA, et al. The potential of adeno-associated viral vectors for gene delivery to muscle tissue. Expert Opin Drug Deliv 2014; 11:345-364.
37. Rodino-Klapac LR, Janssen PM, Montgomery CL, 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. J Transl Med 2007;5:45.
38. Pozsgai ER, Griffin DA, Heller KN, et al. Systemic AAV-mediated beta-sarcoglycan delivery targeting cardiac and skeletal muscle ameliorates histological and functional deficits in LGMD2E mice. Mol Ther 2017;25:855-869.
39. Clark KR, Liu X, McGrath JP, et al. Highly purified recombinant adeno-associated virus vectors are biologically active and free of detectable helper and wild-type viruses. Hum Gene Ther 1999;10: 1031-1039.
40. Ghosh A, Yue Y, Long C, et al. Efficient whole-body transduction with trans-splicing adeno-associated viral vectors. Mol Ther 2007;15:750-755.
41. Emmerling VV, Fischer S, Kleemann M, et al. miR-483 is a self-regulating microRNA and can activate its own expression via USF1 in HeLa cells. Int J Biochem Cell Biol 2016;80:81-86.
42. Toromanoff A, Cherel Y, Guilbaud M, et al. Safety and efficacy of regional intravenous (RI) versus intramuscular (IM) delivery of rAAV1 and rAAV8 to nonhuman primate skeletal muscle. Mol Ther 2008; 16:1291-1299.
43. Rodino-Klapac LR, Montgomery CL, Bremer WG, et al. Persistent expression of FLAG-tagged micro dystrophin in nonhuman primates following intramuscular and vascular delivery. Mol Ther 2010; 18:109-117.
44. Schnepp BC, Jensen RL, Chen CL, et al. Characterization of adeno-associated virus genomes isolated from human tissues. J Virol 2005;79: 14793-14803.
45. Labikova J, Vcelakova J, Ulmannova T, et al. The cytokine production of peripheral blood mononuclear cells reflects the autoantibody profile of patients suffering from type 1 diabetes. Cytokine 2014;69:189-195.
46. Roche JA, Ru LW, O'Neill AM, et al. Unmasking potential intracellular roles for dysferlin through improved immunolabeling methods. J Histochem Cytochem 2011;59:964-975.
47. Vontzalidis A, Terzis G, Manta P. Increased dysferlin expression in Duchenne muscular dystrophy. Anal Quant Cytopathol Histpathol 2014;36:15-22.
48. Nagy N, Nonneman RJ, Llanga T, et al. Hip region muscular dystrophy and emergence of motor deficits in dysferlin-deficient Bla/J mice. Physiol Rep 2017;5.