AAV.Dysferlin Overlap Vectors Restore Function in Dysferlinopathy Animal Models
Open accessAbstract
OBJECTIVE: Dysferlinopathies are a family of untreatable muscle disorders caused by mutations in the dysferlin gene. Lack of dysferlin protein results in progressive dystrophy with chronic muscle fiber loss, inflammation, fat replacement, and fibrosis; leading to deteriorating muscle weakness. The objective of this work is to demonstrate efficient and safe restoration of dysferlin expression following gene therapy treatment. METHODS: Traditional gene therapy is restricted by the packaging capacity limit of adeno-associated virus (AAV), however, use of a dual vector strategy allows for delivery of over-sized genes, including dysferlin. The two vector system (AAV.DYSF.DV) packages the dysferlin cDNA utilizing AAV serotype rh.74 through the use of two discrete vectors defined by a 1 kb region of homology. Delivery of AAV.DYSF.DV via intramuscular and vascular delivery routes in dysferlin deficient mice and nonhuman primates was compared for efficiency and safety. RESULTS: Treated muscles were tested for dysferlin expression, overall muscle histology, and ability to repair following injury. High levels of dysferlin overexpression was shown for all muscle groups treated as well as restoration of functional outcome measures (membrane repair ability and diaphragm specific force) to wild-type levels. In primates, strong dysferlin expression was demonstrated with no safety concerns. INTERPRETATION: Treated muscles showed high levels of dysferlin expression with functional restoration with no evidence of toxicity or immune response providing proof of principle for translation to dysferlinopathy patients.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Overlapping vectors work particularly well in muscle tissue, ameliorating phenotypes linked to Duchenne muscular dystrophy and dysferlinopathies.
“This strategy was shown to work particularly well in muscle tissue, ameliorating phenotypes linked to Duchenne muscular dystrophy (DMD) [43][44][45] and dysferlinopathies [46][47][48].”
From Circumventing the packaging limit of AAV-mediated gene replacement therapy for neurological disorders (2022) · cites this paper as [46]
Two overlapping AAV vectors encoding a dysferlin expression cassette produced high levels of muscle transduction.
“the authors found high levels of muscle transduction with two overlapping AAV vectors encoding a dysferlin expression cassette ( dysferlin has a cDNA size of 6.5 kb and the overlap between the two vectors was * 1kb). 44”
From Expressing Transgenes That Exceed the Packaging Capacity of Adeno-Associated Virus Capsids (2016) · cites this paper as [44]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
Effect of genome size on AAV vector packaging
Wu, Z., Yang, H., & Colosi, P. (2010) · Molecular Therapy · doi:10.1038/mt.2009.255 · Cited by 1,025 · see citing works
Defective membrane repair in dysferlin-deficient muscular dystrophy
Bansal, D., Miyake, K., Vogel, S. S., Groh, S., Chen, C.-C., Williamson, R., McNeil, P. L., & Campbell, K. P. (2003) · Nature · doi:10.1038/nature01573 · Cited by 1,022 · cited 2× · see citing works
“As skeletal muscle is mechanically active, this deficit in repair leads to regeneration/degeneration of fibers with muscle fiber necrosis/loss, and progressive limb weakness.(19,20) Recent years have shown profound development of adeno-associated viral (AAV) gene transfer.”
BackgroundLiu, J., Aoki, M., Illa, I., Wu, C., Fardeau, M., Angelini, C. I., Serrano, C., Urtizberea, J. A., Hentati, F., Hamida, M. B., et al. (1998) · Nature Genetics · doi:10.1038/1682 · Cited by 919 · see citing works
Self-citationBashir, R., Britton, S., Strachan, T., Keers, S. M., Vafiadaki, E., Lako, M., Richard, I., Marchand, S., Bourg, N., Argov, Z., et al. (1998) · Nature Genetics · doi:10.1038/1689 · Cited by 685 · see citing works
Dystrophin Immunity in Duchenne's Muscular Dystrophy
Mendell, J. R., Campbell, K., Rodino-Klapac, L., Sahenk, Z., Shilling, C., Lewis, S., Bowles, D., Gray, S., Li, C., Galloway, G., et al. (2010) · New England Journal of Medicine · doi:10.1056/nejmoa1000228 · Cited by 655 · see citing works
Self-citationModular flexibility of dystrophin: Implications for gene therapy of Duchenne muscular dystrophy
Harper, S. Q., Hauser, M. A., DelloRusso, C., Duan, D., Crawford, R. W., Phelps, S. F., Harper, H. A., Robinson, A. S., Engelhardt, J. F., Brooks, S. V., et al. (2002) · Nature Medicine · doi:10.1038/nm0302-253 · Cited by 580 · see citing works
New recombinant serotypes of AAV vectors
Gao, G., Vandenberghe, L., & Wilson, J. (2005) · Current Gene Therapy · doi:10.2174/1566523054065057 · Cited by 487 · see citing works
Dysferlin Interacts with Annexins A1 and A2 and Mediates Sarcolemmal Wound-healing
Lennon, N. J., Kho, A. T., Bacskai, B. J., Perlmutter, S. L., Hyman, B. T., & Brown, R. H. (2003) · Journal of Biological Chemistry · doi:10.1074/jbc.m307247200 · Cited by 407 · cited 1× · see citing works
“As skeletal muscle is mechanically active, this deficit in repair leads to regeneration/degeneration of fibers with muscle fiber necrosis/loss, and progressive limb weakness.(19,20) Recent years have shown profound development of adeno-associated viral (AAV) gene transfer.”
BackgroundAllocca, M., Doria, M., Petrillo, M., Colella, P., Garcia-Hoyos, M., Gibbs, D., Kim, S. R., Maguire, A., Rex, T. S., Di Vicino, U., et al. (2008) · Journal of Clinical Investigation · doi:10.1172/jci34316 · Cited by 292 · see citing works
Phenotypic Study in 40 Patients With Dysferlin Gene Mutations
Nguyen, K., Bassez, G., Krahn, M., Bernard, R., Laforêt, P., Labelle, V., Urtizberea, J. A., Figarella-Branger, D. F., Romero, N. B., Attarian, S., et al. (2007) · Archives of Neurology · doi:10.1001/archneur.64.8.1176 · Cited by 269 · cited 2× · see citing works
“Although dysferlinopathies are slowly progressing disorders, approximately one-third of patients become wheelchair-dependent within 15 years of disease onset.(7,10) There is no cure for these diseases and limited treatment options are available.”
BackgroundMendell, J. R., Rodino‐Klapac, L. R., Rosales, X. Q., Coley, B. D., Galloway, G., Lewis, S., Malik, V., Shilling, C., Byrne, B. J., Conlon, T., et al. (2010) · Annals of Neurology · doi:10.1002/ana.22251 · Cited by 248 · see citing works
Self-citationCharacterization of Adeno-Associated Virus Genomes Isolated from Human Tissues
Schnepp, B. C., Jensen, R. L., Chen, C.-L., Johnson, P. R., & Clark, K. R. (2005) · Journal of Virology · doi:10.1128/jvi.79.23.14793-14803.2005 · Cited by 231 · cited 1× · see citing works
“was used to determine an encapsulated vg titer utilizing a Prism 7500 Fast Taqman detector system (PE Applied Biosystems Grand Island, NY USA).(40) The following primers/probes were used: AAVrh.”
MethodSelf-citationCharacterization of Genome Integrity for Oversized Recombinant AAV Vector
Dong, B., Nakai, H., & Xiao, W. (2010) · Molecular Therapy · doi:10.1038/mt.2009.258 · Cited by 230 · see citing works
Limb‐girdle muscular dystrophy type 2D gene therapy restores α‐sarcoglycan and associated proteins
Mendell, J. R., Rodino‐Klapac, L. R., Rosales, X. Q., Kota, J., Coley, B. D., Galloway, G. M., Craenen, J. M., Lewis, S., Malik, V., Shilling, C. J., et al. (2009) · Annals of Neurology · doi:10.1002/ana.21732 · Cited by 214 · see citing works
Self-citationHo, M. (2004) · Human Molecular Genetics · doi:10.1093/hmg/ddh212 · Cited by 201 · cited 1× · see citing works
“As previously reported, Dysf / mice demonstrate mild pathology at young ages seen primarily in small numbers of centrally nucleated fibers and isolated necrotic fibers.(19,45) Following gene transfer with AAVrh.”
BackgroundDuan, D., Yue, Y., Yan, Z., & Engelhardt, J. F. (2000) · Nature Medicine · doi:10.1038/75080 · Cited by 200 · see citing works
Efficient recovery of dysferlin deficiency by dual adeno-associated vector-mediated gene transfer
Lostal, W., Bartoli, M., Bourg, N., Roudaut, C., Bentaïb, A., Miyake, K., Guerchet, N., Fougerousse, F., McNeil, P., & Richard, I. (2010) · Human Molecular Genetics · doi:10.1093/hmg/ddq065 · Cited by 173 · cited 3× · see citing works
“In their work, the low levels of dysferlin expression were not sufficient to restore functional measures to WT levels which led them to postulate that levels of 30% dysferlin expression would be necessary for clinically meaningful outcomes.(46) Following this work, we tested both low (2 9 10(12)vg) and high (6 9 10(12…”
BackgroundInfluentialQuantitative neuropathological changes in presymptomatic Huntington's disease
Gómez‐Tortosa, E., MacDonald, M. E., Friend, J. C., Taylor, S. A., Weiler, L., Cupples, L. A., Srinidhi, J., Gusella, J. F., Bird, E. D., Vonsattel, J., et al. (2001) · Annals of Neurology · doi:10.1002/1531-8249(200101)49:1 · Cited by 170 · see citing works
Chicoine, L., Montgomery, C., Bremer, W., Shontz, K., Griffin, D., Heller, K., Lewis, S., Malik, V, Grose, W., Shilling, C., et al. (2014) · Molecular Therapy · doi:10.1038/mt.2013.244 · Cited by 167 · cited 1× · see citing works
“In addition, previous work has shown that pre-existing immunity to the vector capsid results in diminished to absent expression of the transgene.(48) Thus, primates were prescreened prior to treatment for circulating binding antibodies to AAVrh.”
BackgroundSelf-citationFollistatin Gene Delivery Enhances Muscle Growth and Strength in Nonhuman Primates
Kota, J., Handy, C. R., Haidet, A. M., Montgomery, C. L., Eagle, A., Rodino‐Klapac, L. R., Tucker, D., Shilling, C. J., Therlfall, W. R., Walker, C. M., et al. (2009) · Science Translational Medicine · doi:10.1126/scitranslmed.3000112 · Cited by 166 · see citing works
Self-citationEvidence for the Failure of Adeno-associated Virus Serotype 5 to Package a Viral Genome ≥8.2 kb
Lai, Y., Yue, Y., & Duan, D. (2010) · Molecular Therapy · doi:10.1038/mt.2009.256 · Cited by 166 · see citing works
Lek, A., Evesson, F. J., Sutton, R. B., North, K. N., & Cooper, S. T. (2011) · Traffic · doi:10.1111/j.1600-0854.2011.01267.x · Cited by 164 · see citing works
Wells, D. J., Wells, K. E., Asante, E. A., Turner, G., Sunada, Y., Campbell, K. P., Walsh, F. S., & Dickson, G. (1995) · Human Molecular Genetics · doi:10.1093/hmg/4.8.1245 · Cited by 155 · see citing works
Genomic organization of the dysferlin gene and novel mutations in Miyoshi myopathy
Aoki, M., Liu, J., Richard, I., Bashir, R., Britton, S., Keers, S. M., Oeltjen, J., Brown, H. E. V., Marchand, S., Bourg, N., et al. (2001) · Neurology · doi:10.1212/wnl.57.2.271 · Cited by 150 · see citing works
Self-citationRafael‐Fortney, J. A., Chimanji, N. S., Schill, K. E., Martin, C. D., Murray, J. D., Ganguly, R., Stangland, J. E., Tran, T., Xu, Y., Canan, B. D., et al. (2011) · Circulation · doi:10.1161/circulationaha.111.031716 · Cited by 138 · see citing works
AAV1.NT-3 Gene Therapy for Charcot–Marie–Tooth Neuropathy
Sahenk, Z., Galloway, G. M., Clark, K. R., Malik, V., Rodino‐Klapac, L. R., Kaspar, B. K., Chen, L., Braganza, C., Montgomery, C. L., & Mendell, J. R. (2013) · Molecular Therapy · doi:10.1038/mt.2013.250 · Cited by 104 · see citing works
Self-citationKoo, T., Popplewell, L., Athanasopoulos, T., & Dickson, G. (2014) · Human Gene Therapy · doi:10.1089/hum.2013.164 · Cited by 104 · see citing works
Rodino‐Klapac, L. R., Janssen, P. M. L., Montgomery, C. L., Coley, B. D., Chicoine, L. G., Clark, K. R., & Mendell, J. R. (2007) · Journal of Translational Medicine · doi:10.1186/1479-5876-5-45 · Cited by 104 · cited 2× · see citing works
“DV (1 9 10(12)vg of each vector) in 100 lL normal saline as previously described.(41) Animals were sacrificed 4 weeks postinjection to study dysferlin expression.”
Self-citationEfficient gene delivery to the cone-enriched pig retina by dual AAV vectors
Colella, P., Trapani, I., Cesi, G., Sommella, A., Manfredi, A., Puppo, A., Iodice, C., Rossi, S., Simonelli, F., Giunti, M., et al. (2014) · Gene Therapy · doi:10.1038/gt.2014.8 · Cited by 103 · see citing works
Treatment of dysferlinopathy with deflazacort: a double-blind, placebo-controlled clinical trial
Walter, M. C., Reilich, P., Thiele, S., Schessl, J., Schreiber, H., Reiners, K., Kreß, W., Müller‐Reible, C., Vorgerd, M., Urban, P. P., et al. (2013) · Orphanet Journal of Rare Diseases · doi:10.1186/1750-1172-8-26 · Cited by 100 · cited 1× · see citing works
“been previously successful for Duchenne muscular dystrophy patients, is ineffective and not warranted.(11) Although it has been occasionally reported that treatment with IV-IG or rituximab therapies can be effective by modifying the immune response, to date there remains no cure.”
BackgroundNovel diagnostic features of dysferlinopathies
Rosales, X. Q., Gastier, J. M., Lewis, S., Malik, V., Thrush, D. L., Astbury, C., Pyatt, R. E., Reshmi, S. C., Sahenk, Z., & Mendell, J. R. (2010) · Muscle & Nerve · doi:10.1002/mus.21650 · Cited by 99 · see citing works
Self-citationRodino‐Klapac, L. R., Montgomery, C. L., Bremer, W. G., Shontz, K. M., Malik, V., Davis, N., Sprinkle, S. L., Campbell, K. J., Sahenk, Z., Clark, K. R., et al. (2009) · Molecular Therapy · doi:10.1038/mt.2009.254 · Cited by 97 · see citing works
Self-citationUrtizberea, J., Bassez, G., Leturcq, F., Nguyen, K., Krahn, M., & Lévy, N. (2008) · Neurology India · doi:10.4103/0028-3886.43447 · Cited by 81 · see citing works
Grose, W. E., Clark, K. R., Griffin, D., Malik, V., Shontz, K. M., Montgomery, C. L., Lewis, S., Brown, R. H., Janssen, P. M. L., Mendell, J. R., et al. (2012) · PLoS ONE · doi:10.1371/journal.pone.0039233 · Cited by 76 · cited 10× · see citing works
“DYSF (Table 1).(16) Western blot analysis showed a well-defined 237 kDa band for treated muscles which was absent for PBS control-treated animals (Fig.”
BackgroundMethodInfluentialSelf-citationDysferlin at transverse tubules regulates Ca2+ homeostasis in skeletal muscle
Kerr, J. P., Ward, C. W., & Bloch, R. J. (2014) · Frontiers in Physiology · doi:10.3389/fphys.2014.00089 · Cited by 73 · see citing works
Chicoine, L. G., Rodino‐Klapac, L. R., Shao, G., Xu, R., Bremer, W. G., Camboni, M., Golden, B., Montgomery, C. L., Shontz, K. M., Heller, K. N., et al. (2013) · Molecular Therapy · doi:10.1038/mt.2013.246 · Cited by 73 · cited 1× · see citing works
“74 transduces muscle very efficiently when delivered through the vasculature.(25) This lays the foundation for future translation to clinical practice as it allows for treatment of multiple muscle groups.”
BackgroundSelf-citationLate onset in dysferlinopathy widens the clinical spectrum
Klinge, L., Dean, A., Kress, W., Dixon, P., Charlton, R., Müller, J., Anderson, L. V., Straub, V. W., Barresi, R., Lochmüller, H., et al. (2008) · Neuromuscular Disorders · doi:10.1016/j.nmd.2008.01.004 · Cited by 67 · cited 1× · see citing works
“In general, patients present with an abrupt onset in the second decade with progressive involvement of proximal and distal musculature.(9,10) Although dysferlinopathies are slowly progressing disorders, approximately one-third of patients become wheelchair-dependent within 15 years of disease onset.”
BackgroundPhylogenetic analysis of ferlin genes reveals ancient eukaryotic origins
Lek, A., Lek, M., North, K., & Cooper, S. (2010) · BMC Evolutionary Biology · doi:10.1186/1471-2148-10-231 · Cited by 67 · cited 2× · see citing works
“The DYSF gene consists of 55 exons encompassing 150 kb of genomic DNA.14 The associated cDNA is ~6.5 kb and codes for the dysferlin protein.2,14–16 Dysferlin, a member of the ferlin family, is composed of seven N-terminal C2 domains with a transmembrane C-terminus.17,18 Dysferlin has multiple roles in skeletal muscle…”
BackgroundInfluentialmdx Mice Manifest More Severe Muscle Dysfunction and Diaphragm Force Deficits than Do mdx Mice
Beastrom, N., Lu, H., Macke, A., Canan, B. D., Johnson, E. K., Penton, C. M., Kaspar, B. K., Rodino‐Klapac, L. R., Zhou, L., Janssen, P. M. L., et al. (2011) · American Journal Of Pathology · doi:10.1016/j.ajpath.2011.07.009 · Cited by 67 · cited 1× · see citing works
“Mice were euthanized and the diaphragm was dissected with rib attachments and central tendon intact, and placed in K-H buffer at 37°C as previously described.(42,43) A 1–2 mm wide section (length from rib to tendon) of diaphragm was isolated and attached to a force transducer.”
MethodSelf-citationQuantitation of the Calcium and Membrane Binding Properties of the C2 Domains of Dysferlin
Abdullah, N., Padmanarayana, M., Marty, N. J., & Johnson, C. P. (2014) · Biophysical Journal · doi:10.1016/j.bpj.2013.11.4492 · Cited by 61 · cited 2× · see citing works
“The DYSF gene consists of 55 exons encompassing 150 kb of genomic DNA.14 The associated cDNA is ~6.5 kb and codes for the dysferlin protein.2,14–16 Dysferlin, a member of the ferlin family, is composed of seven N-terminal C2 domains with a transmembrane C-terminus.17,18 Dysferlin has multiple roles in skeletal muscle…”
BackgroundInfluentialFuson, K. L., Rice, A. M., Mahling, R. W., Snow, A., Nayak, K., Shanbhogue, P., Meyer, A. G., Redpath, G., Hinderliter, A. K., Cooper, S. T., et al. (2013) · Structure · doi:10.1016/j.str.2013.10.001 · Cited by 59 · see citing works
Efficient Whole-body Transduction with Trans-splicing Adeno-associated Viral Vectors.
Ghosh, A., Yue, Y., Long, C., Bostick, B., & Duan, D. (2007) · Molecular Therapy · doi:10.1038/sj.mt.6300153 · Cited by 53 · see citing works
Dysferlin and Animal Models for Dysferlinopathy
Kobayashi, K., Izawa, T., Kuwamura, M., & Yamate, J. (2012) · Journal of Toxicologic Pathology · doi:10.1293/tox.25.135 · Cited by 47 · cited 1× · see citing works
“LGMDs comprise 30% of all progressive muscular dystrophies with LGMD2B as the most frequently diagnosed dysferlinopathy.(7,8) Mutations in DYSF lead to a progressive muscular dystrophy with chronic muscle fiber loss, inflammation, fat replacement, and fibrosis, all contributing to deteriorating weakness.”
BackgroundDysferlinopathy course and sportive activity: clues for possible treatment.
Angelini, C. I., Peterle, E., Gaiani, A., Bortolussi, L., & Borsato, C. (2011) · PubMed Central · Cited by 46 · see citing works
Complete fatty degeneration of lumbar erector spinae muscles caused by a primary dysferlinopathy
Seror, P., Krahn, M., Laforêt, P., Leturcq, F., & Maisonobe, T. (2007) · Muscle & Nerve · doi:10.1002/mus.20910 · Cited by 44 · see citing works
Dysferlin overexpression in skeletal muscle produces a progressive myopathy
Glover, L. E., Newton, K. P., Krishnan, G., Bronson, R. T., Boyle, A., Krivickas, L. S., & Brown, R. H. (2009) · Annals of Neurology · doi:10.1002/ana.21926 · Cited by 43 · cited 2× · see citing works
“Monitoring an immune response was critical as previous work demonstrated toxicity and progressive myopathy in cases of transgene overexpression.(39) In addition, previous work has shown that pre-existing immunity to the vector capsid results in diminished to absent expression of the transgene.”
BackgroundMethodHeller, K. N., Montgomery, C. L., Janssen, P. M. L., Clark, K. R., Mendell, J. R., & Rodino‐Klapac, L. R. (2013) · Molecular Therapy · doi:10.1038/mt.2012.281 · Cited by 42 · see citing works
Self-citationEffects of rituximab in two patients with dysferlin-deficient muscular dystrophy
Lerario, A., Cogiamanian, F. M., Marchesi, C., Belicchi, M., Bresolin, N., Porretti, L., & Torrente, Y. (2010) · BMC Musculoskeletal Disorders · doi:10.1186/1471-2474-11-157 · Cited by 42 · cited 1× · see citing works
“Although it has been occasionally reported that treatment with IV-IG or rituximab therapies can be effective by modifying the immune response, to date there remains no cure.(12,13) Thus, the need for a treatment is clear.”
BackgroundDysferlinopathy associated with rigid spine syndrome
Nagashima, T., Chuma, T., Mano, Y., Goto, Y., Hayashi, Y. K., Minami, N., Nishino, I., Nonaka, I., Takahashi, T., Sawa, H., et al. (2004) · Neuropathology · doi:10.1111/j.1440-1789.2004.00573.x · Cited by 41 · see citing works
Efficient whole-body transduction with trans-splicing adeno-associated viral vectors.
Ghosh, A., Yue, Y., Long, C., Bostick, B., & Duan, D. (2007) · Molecular Therapy · doi:10.1038/sj.mt.6300081 · Cited by 41 · see citing works
Pahl, L., Schubert, S., Skawran, B., Sandbothe, M., Schmidtke, J., & Stuhrmann, M. (2013) · Experimental Eye Research · doi:10.1016/j.exer.2013.09.012 · Cited by 39 · see citing works
Fanin, M., Nascimbeni, A. C., & Angelini, C. I. (2006) · Neuromuscular Disorders · doi:10.1016/j.nmd.2006.06.010 · Cited by 30 · cited 1× · see citing works
“This is corroborated by considering carriers of DYSF mutations which have no clinical symptoms of dysferlinopathy but with <50% dysferlin protein expression.(47) After demonstration of robust, wide-spread expression of dysferlin in mouse models, we moved the dual vector treatment strategy into rhesus macaques to study…”
BackgroundAAV-Mediated Gene Therapy to the Isolated Limb in Rhesus Macaques
Rodino‐Klapac, L. R., Montgomery, C. L., Mendell, J. R., & Chicoine, L. G. (2010) · Methods in molecular biology · doi:10.1007/978-1-61737-982-6_19 · Cited by 29 · see citing works
Self-citationDysferlin is essential for endocytosis in the sea star oocyte
Oulhen, N., Onorato, T. M., Ramos, I., & Wessel, G. M. (2013) · Developmental Biology · doi:10.1016/j.ydbio.2013.12.018 · Cited by 16 · cited 1× · see citing works
“Dysferlin has multiple roles in skeletal muscle including sarcolemmal membrane repair,(16,19,20) vesicle trafficking,(21) t-tubule structure and function(22) and endocytosis.(23) Our group(16) and others(19,20,24) have studied the role of dysferlin in Ca-dependent membrane repair, consistently reporting a decrease in…”
BackgroundLiu, J., Wu, C., Bossie, K., Bejaoui, K., Hosler, B. A., Gingrich, J. C., Hamida, M. B., Hentati, F., Schurr, E., de Jong, P. J., et al. (1998) · Genomics · doi:10.1006/geno.1998.5204 · Cited by 16 · see citing works
Self-citationLabiková, J., Včeláková, J., Ulmannová, T., Petruželková, L., Koloušková, S., & Štechová, K. (2014) · Cytokine · doi:10.1016/j.cyto.2014.06.013 · Cited by 10 · cited 1× · see citing works
“Peripheral blood mononuclear cells (PBMCs) were separated from whole blood samples through density gradient centrifugation, as previously described.(44) Briefly, fresh blood samples are spun in a table-top centrifuge (Sorval Legend RT, Thermo Scientific) and the top plasma layer is removed and stored in 80°C freezer.”
MethodSheppard, N. C., Jones, R. B., Burwitz, B. J., Nimityongskul, F. A., Newman, L. P., Buechler, M. B., Reed, J. S., Piaskowski, S. M., Weisgrau, K. L., Castrovinci, P. A., et al. (2014) · PLoS ONE · doi:10.1371/journal.pone.0092012 · Cited by 9 · see citing works
Flagged first, then by citations
Research works printed but not linked: 1
- Illa I Serrano-Munuera C Gallardo E Distal anterior compartment myopathy: a dysferlin mutation causing a new muscular dystrophy phenotype Ann Neurol 2001 49 130 134 11198284
Cited by
Sorted by citations
Adeno-associated virus vector as a platform for gene therapy delivery
Wang, D., Tai, P. W. L., & Gao, G. (2019) · Nature Reviews Drug Discovery · doi:10.1038/s41573-019-0012-9 · Cited by 2,444 · see citing works
Emerging issues in AAV-mediated in vivo gene therapy
Colella, P., Ronzitti, G., & Mingozzi, F. (2018) · Molecular Therapy - Methods & Clinical Development · doi:10.1016/j.omtm.2017.11.007 · Cited by 881 · see citing works
Mendell, J. R., Sahenk, Z., Lehman, K., Nease, C., Lowes, L. P., Miller, N. F., Iammarino, M. A., Alfano, L. N., Nicholl, A., Al-Zaidy, S., et al. (2020) · JAMA Neurology · doi:10.1001/jamaneurol.2020.1484 · Cited by 405 · see citing works
Self-citationGene therapy advances: A meta-analysis of AAV usage in clinical settings
Au, H. K. E., Isalan, M., & Mielcarek, M. (2022) · Frontiers in Medicine · doi:10.3389/fmed.2021.809118 · Cited by 284 · see citing works
Expressing Transgenes That Exceed the Packaging Capacity of Adeno-Associated Virus Capsids
Chamberlain, K., Riyad, J. M., & Weber, T. (2016) · Human Gene Therapy Methods · doi:10.1089/hgtb.2015.140 · Cited by 141 · see citing works
“provided another example of the successful use of an overlapping vector system to overexpress genes that exceed the packaging capacity of a single AAV vector.(44) In this study, the authors found high levels of muscle transduction with two overlapping AAV vectors encoding a dysferlin expression cassette (dysferlin has…”
BackgroundMethodCurrent clinical applications of AAV-mediated gene therapy
Byrne, B. J., Flanigan, K. M., Matesanz, S. E., Finkel, R. S., Waldrop, M. A., D'Ambrosio, E. S., Johnson, N. E., Smith, B. K., Bönnemann, C. G., Carrig, S., et al. (2025) · Molecular Therapy · doi:10.1016/j.ymthe.2025.04.045 · Cited by 134 · see citing works
“115 This paved the way for an open-label, phase 1, single dose, intravenous gene transfer study of rAAVrh74.”
The Classification, Natural History and Treatment of the Limb Girdle Muscular Dystrophies
Murphy, A. P., & Straub, V. W. (2015) · Journal of Neuromuscular Diseases · doi:10.3233/jnd-150105 · Cited by 114 · see citing works
Defective membrane fusion and repair in Anoctamin5 -deficient muscular dystrophy
Griffin, D. A., Johnson, R. W., Whitlock, J. M., Pozsgai, E. R., Heller, K. N., Grose, W. E., Arnold, W. D., Sahenk, Z., Hartzell, H. C., & Rodino‐Klapac, L. R. (2016) · Human Molecular Genetics · doi:10.1093/hmg/ddw063 · Cited by 103 · see citing works
“Membrane damage was assessed by accumulation of FM1-43, a membrane-impermeant styryl cationic dye that is not fluorescent in aqueous solution but fluoresces brightly in a lipid environment and has been used extensively to studymembrane repair (9,33,34).”
MethodSelf-citationAdeno-associated Virus (AAV) Dual Vector Strategies for Gene Therapy Encoding Large Transgenes.
McClements, M. E., & MacLaren, R. E. (2017) · PubMed Central · Cited by 95 · see citing works
Potter, R. A., Griffin, D. A., Heller, K. N., Peterson, E. L., Clark, E. K., Mendell, J. R., & Rodino‐Klapac, L. R. (2021) · Human Gene Therapy · doi:10.1089/hum.2019.255 · Cited by 82 · see citing works
Self-citationDysferlin mediates membrane tubulation and links T-tubule biogenesis to muscular dystrophy
Hofhuis, J., Bersch, K., Büssenschütt, R., Drzymalski, M. A., Liebetanz, D., Nikolaev, V. O., Wagner, S., Maier, L. S., Gärtner, J., Klinge, L., et al. (2017) · Journal of Cell Science · doi:10.1242/jcs.198861 · Cited by 78 · see citing works
“So far, no treatments for the cause of these diseases are available, but recent gene transfer approaches are able to restore proper localization of the dysferlin full-length protein (Escobar et al., 2016; Pryadkina et al., 2015; Sondergaard et al., 2015).”
BackgroundPotter, R. A., Griffin, D. A., Sondergaard, P. C., Johnson, R. W., Pozsgai, E. R., Heller, K. N., Peterson, E. L., Lehtimäki, K. K., Windish, H. P., Mittal, P., et al. (2017) · Human Gene Therapy · doi:10.1089/hum.2017.062 · Cited by 78 · see citing works
“9,11 The 5 ¢ cassette contains the MHCK7 promoter, the chimeric intron, and the first 3370 bp of the dysferlin cDNA flanked by AAV2 inverted terminal repeats.”
InfluentialSelf-citationKodippili, K., Hakim, C. H., Pan, X., Yang, H. T., Yue, Y., Zhang, Y., Shin, J., Yang, N. N., & Duan, D. (2017) · Human Gene Therapy · doi:10.1089/hum.2017.095 · Cited by 80 · see citing works
Pozsgai, E. R., Griffin, D. A., Heller, K. N., Mendell, J. R., & Rodino-Klapac, L. R. (2017) · Molecular Therapy · doi:10.1016/j.ymthe.2017.02.013 · Cited by 76 · see citing works
Self-citationCárdenas, A. M., González‐Jamett, A. M., Cea, L. A., Bevilacqua, J. A., & Caviedes, P. A. (2016) · Experimental Neurology · doi:10.1016/j.expneurol.2016.06.026 · Cited by 73 · see citing works
Gushchina, L. V., Bhattacharya, S., McElhanon, K. E., Choi, J. H., Manring, H. R., Beck, E. X., Alloush, J., & Weisleder, N. L. (2017) · Molecular Therapy · doi:10.1016/j.ymthe.2017.06.025 · Cited by 70 · see citing works
Genome engineering: a new approach to gene therapy for neuromuscular disorders
Nelson, C. E., Robinson-Hamm, J. N., & Gersbach, C. A. (2017) · Nature Reviews Neurology · doi:10.1038/nrneurol.2017.126 · Cited by 71 · see citing works
Progress and prospects of gene therapy clinical trials for the muscular dystrophies
Bengtsson, N. E., Seto, J. T., Hall, J. K., Chamberlain, J. S., & Odom, G. L. (2015) · Human Molecular Genetics · doi:10.1093/hmg/ddv420 · Cited by 70 · see citing works
“Recent studies optimizing rAAV-mediated delivery of full-length human dysferlin in dysferlin-null mice suggest promising future therapies for LGMD2B,MiyoshiMyopathy (MM1) and distal anterior compartment myopathy (33).”
BackgroundThe Limb–Girdle Muscular Dystrophies: Is Treatment on the Horizon?
Chu, M. L., & Moran, E. S. (2018) · Neurotherapeutics · doi:10.1007/s13311-018-0648-x · Cited by 66 · see citing works
“of membrane repair ability with no apparent toxicity or systemic immune rejection [29].”
BackgroundLimb–Girdle Muscular Dystrophies Classification and Therapies
Bouchard, C., & Tremblay, J. P. (2023) · Journal of Clinical Medicine · doi:10.3390/jcm12144769 · Cited by 67 · see citing works
Design of AAV Vectors for Delivery of Large or Multiple Transgenes
Patel, A., Zhao, J., Duan, D., & Lai, Y. (2019) · Methods in molecular biology · doi:10.1007/978-1-4939-9139-6_2 · Cited by 64 · see citing works
Fichna, J. P., Macias, A., Piechota, M., Korostyński, M., Potulska‐Chromik, A., Rędowicz, M. J., & Żekanowski, C. (2018) · Human Genomics · doi:10.1186/s40246-018-0167-1 · Cited by 57 · see citing works
Marrone, L., Marchi, P. M., & Azzouz, M. (2022) · Expert Opinion on Biological Therapy · doi:10.1080/14712598.2022.2012148 · Cited by 56 · see citing works
Structure-Based Designed Nano-Dysferlin Significantly Improves Dysferlinopathy in BLA/J Mice
Llanga, T., Nagy, N., Conatser, L., Dial, C. F., Sutton, R. B., & Hirsch, M. L. (2017) · Molecular Therapy · doi:10.1016/j.ymthe.2017.05.013 · Cited by 52 · see citing works
“Despite these two major concerns with AAV large gene transduction, preclinical data in a dysferlin-deficient mouse have led to recruitment of dysferlinopathy patients for a phase 1 clinical trial proposing the use of AAV-oversized transduction for the treatment of dysferlinopathy.(6,17) Notably, this will be the first…”
BackgroundMethodResultInfluentialKolesnik, V. V., Nurtdinov, R. F., Oloruntimehin, E. S., Karabelsky, A. V., & Malogolovkin, A. S. (2024) · Clinical and Translational Medicine · doi:10.1002/ctm2.1607 · Cited by 51 · see citing works
“86,91 101 Several approaches can be successfully used to assemble large transgene in multiple AAV vectors.”
BackgroundSellers, S., Milad, N., White, Z. R., Pascoe, C. D., Chan, R., Payne, G. W., Seow, C. Y., Rossi, F. M. V., Seidman, M. A., & Bernatchez, P. N. (2017) · Journal of Lipid Research · doi:10.1194/jlr.m079459 · Cited by 47 · see citing works
“is that contrary to studies that found significant impairment of locomotor function (38, 39) and muscle function ex vivo”
ResultDual and triple AAV delivery of large therapeutic gene sequences into the inner ear
Akil, O. (2020) · Hearing Research · doi:10.1016/j.heares.2020.107912 · Cited by 47 · see citing works
Systemic delivery of full-length dystrophin in Duchenne muscular dystrophy mice
Zhou, Y., Zhang, C., Xiao, W., Herzog, R. W., & Han, R. (2024) · Nature Communications · doi:10.1038/s41467-024-50569-6 · Cited by 46 · see citing works
Exon 32 Skipping of Dysferlin Rescues Membrane Repair in Patients’ Cells
Barthélémy, F., Blouin, C. M., Wein, N., Mouly, V., Courrier, S., Dionnet, E., Kergourlay, V., Mathieu, Y., Garcı́a, L., Butler-Browne, G. S., et al. (2015) · Journal of Neuromuscular Diseases · doi:10.3233/jnd-150109 · Cited by 43 · see citing works
“As for some muscular dystrophies, several therapeutic strategies are currently being evaluated for dysferlinopathies, including gene therapy approaches [6, 16–19].”
BackgroundCalcium Mechanisms in Limb-Girdle Muscular Dystrophy with CAPN3 Mutations
Lasa-Elgarresta, J., Mosqueira‐Martín, L., Naldaiz‐Gastesi, N., Sáenz, A., de Munaín, A. L., & Vallejo‐Illarramendi, A. (2019) · International Journal of Molecular Sciences · doi:10.3390/ijms20184548 · Cited by 43 · see citing works
“This vector has been previously used in other gene therapy programs targeting Duchenne Muscular Dystrophy and five other LGMDs [143,144].”
Mendell, J. R., Proud, C. M., Zaidman, C. M., Mason, S., Darton, E., Wang, S., Wandel, C., Murphy, A. P., Mercuri, E. M., Francesco Muntoni, A., et al. (2024) · Pediatric Neurology · doi:10.1016/j.pediatrneurol.2024.01.003 · Cited by 42 · see citing works
Self-citationPotter, R. A., Peterson, E. L., Griffin, D., Cooper-Olson, G., Lewis, S., Cochran, K., Mendell, J. R., & Rodino‐Klapac, L. R. (2024) · Molecular Therapy — Methods & Clinical Development · doi:10.1016/j.omtm.2024.101195 · Cited by 40 · see citing works
“30 34 A quantitative polymerase chain reaction (qPCR)-based titration method based on a supercoiled plasmid standard was used to determine an encapsulated vg titer using a Prism 7500 Fast TaqMan detector system (PE Applied Biosystems, Foster City, CA).”
MethodSelf-citationMyoediting: Toward Prevention of Muscular Dystrophy by Therapeutic Genome Editing
Zhang, Y., Long, C., Bassel‐Duby, R., & Olson, E. N. (2018) · Physiological Reviews · doi:10.1152/physrev.00046.2017 · Cited by 40 · see citing works
“After administration of the dual recombinant AAV vectors, fulllength dysferlin transcripts were shown to be produced by either trans-splicing or homologous recombination (133, 232, 370).”
BackgroundUnmet Needs and Evolving Treatment for Limb Girdle Muscular Dystrophies
Pozsgai, E. R., Griffin, D., Potter, R. A., Sahenk, Z., Lehman, K. J., Rodino‐Klapac, L. R., & Mendell, J. R. (2021) · Neurodegenerative Disease Management · doi:10.2217/nmt-2020-0066 · Cited by 37 · see citing works
Self-citationRescue of GSDIII Phenotype with Gene Transfer Requires Liver- and Muscle-Targeted GDE Expression
Vidal, P., Pagliarani, S., Colella, P., Verdera, H. C., Jauze, L., Gjorgjieva, M., Puzzo, F., Marmier, S., Collaud, F., Sola, M. S., et al. (2017) · Molecular Therapy · doi:10.1016/j.ymthe.2017.12.019 · Cited by 37 · see citing works
Goedeker, N. L., Dharia, S. D., Griffin, D. A., Coy, J., Truesdale, T., Parikh, R., Whitehouse, K., Santra, S., Asher, D. R., & Zaidman, C. M. (2023) · Therapeutic Advances in Neurological Disorders · doi:10.1177/17562864221149781 · Cited by 37 · see citing works
Self-citationGene therapy for genetic diseases: challenges and future directions
Beibei, Q. I. E., Tuo, J., Chen, F., Ding, H., & Lyu, L. (2025) · MedComm · doi:10.1002/mco2.70091 · Cited by 37 · see citing works
Hip region muscular dystrophy and emergence of motor deficits in dysferlin‐deficient Bla/J mice
Nagy, N., Nonneman, R. J., Llanga, T., Dial, C. F., Riddick, N. V., Hampton, T. G., Moy, S. S., Lehtimäki, K. K., Ahtoniemi, T., Puoliväli, J. T., et al. (2017) · Physiological Reports · doi:10.14814/phy2.13173 · Cited by 32 · see citing works
“…investigation for which relevant representative animal models, showing patientlike pathologies, are necessary to determine efficacy (Krahn et al. 2009; Lostal et al. 2010; Wein et al. 2010; Grose et al. 2012; Hirsch et al. 2013; Dominov et al. 2014; Pryadkina et al. 2015; Sondergaard et al. 2015).”
Portrait of Dysferlinopathy: Diagnosis and Development of Therapy
Bouchard, C., & Tremblay, J. P. (2023) · Journal of Clinical Medicine · doi:10.3390/jcm12186011 · Cited by 31 · see citing works
“The study was first conducted on mice and non-human primates and showed restored dysferlin expression in all muscle groups, as well as a restored function measured by membrane repair and diaphragm strength [87].”
BackgroundEscobar, H., Schoewel, V., Spuler, S., Marg, A., & Izsvák, Z. (2016) · Molecular Therapy — Nucleic Acids · doi:10.1038/mtna.2015.52 · Cited by 30 · see citing works
Ferlin Overview: From Membrane to Cancer Biology
Peulen, O., Rademaker, G., Anania, S., Turtoï, A., Bellahcène, A., & Castronovo, V. (2019) · Cells · doi:10.3390/cells8090954 · Cited by 27 · see citing works
Correction of pseudoexon splicing caused by a novel intronic dysferlin mutation
Dominov, J. A., Uyan, Ö., McKenna-Yasek, D. M., Nallamilli, B. R. R., Kergourlay, V., Bartoli, M., Lévy, N., Hudson, J. A., Evangelista, T., Lochmüller, H., et al. (2019) · Annals of Clinical and Translational Neurology · doi:10.1002/acn3.738 · Cited by 24 · see citing works
Griffin, D. A., Pozsgai, E. R., Heller, K. N., Potter, R. A., Peterson, E. L., & Rodino‐Klapac, L. R. (2020) · Human Gene Therapy · doi:10.1089/hum.2019.199 · Cited by 23 · see citing works
Self-citationSerum exosomes can restore cellular function in vitro and be used for diagnosis in dysferlinopathy
Dong, X., Gao, X., Dai, Y., Ran, N., & Yin, H. (2018) · Theranostics · doi:10.7150/thno.22856 · Cited by 22 · see citing works
“Although adeno-associated virus (AAV) vector systems have been developed to deliver full-length or nano-sized dysferlin genes into dysferlin-deficient mice and non-human primates with encouraging results [9, 10], AAV can trigger immune response that limits its therapeutic efficacy upon repeat treatment.”
BackgroundNitzahn, M., Allegri, G., Khoja, S., Truong, B., Makris, G., Häberle, J., & Lipshutz, G. S. (2020) · Molecular Therapy · doi:10.1016/j.ymthe.2020.04.011 · Cited by 19 · see citing works
In vivo Dominant-Negative Effect of an SCN5A Brugada Syndrome Variant
Doisne, N., Grauso, M., Mougenot, N., Clergue, M., Souil, C., Coulombe, A., Guicheney, P., & Neyroud, N. (2021) · Frontiers in Physiology · doi:10.3389/fphys.2021.661413 · Cited by 18 · see citing works
Seo, Y.-E., Baine, S. H., Kempton, A. N., Rogers, O. C., Lewis, S., Adegboye, K., Haile, A., Griffin, D. A., Peterson, E. L., Pozsgai, E. R., et al. (2023) · Molecular Therapy — Methods & Clinical Development · doi:10.1016/j.omtm.2023.01.004 · Cited by 18 · see citing works
“The hSGCG expression cassette was cloned between AAV2 ITRs, and the cassette was packaged into an rAAVrh74 vector using a triple transfection method in the Vector Manufacturing Facility in the Center for Gene Therapy at Nationwide Children’s Hospital, as previously described.(13,40,41)”
MethodSelf-citationAnwar, S., & Yokota, T. (2024) · Biomolecules · doi:10.3390/biom14030256 · Cited by 18 · see citing works
Mitrani-Rosenbaum, S., Yakovlev, L., Becker‐Cohen, M., Argov, Z., Fellig, Y., & Harazi, A. (2021) · Journal of Neuromuscular Diseases · doi:10.3233/jnd-210755 · Cited by 18 · see citing works
The Dysferlin Transcript Containing the Alternative Exon 40a is Essential for Myocyte Functions
Ballouhey, O., Courrier, S., Kergourlay, V., Gorokhova, S., Cérino, M., Krahn, M., Lévy, N., & Bartoli, M. (2021) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2021.754555 · Cited by 17 · see citing works
“Currently, the therapeutic studies conducted only restored the main transcript of dysferlin (transcript 1) (Lostal et al., 2010; Sondergaard et al., 2015; Potter et al., 2018).”
BackgroundMolecular diagnosis of muscular diseases in outpatient clinics
Thuriot, F., Gravel, E., Buote, C., Doyon, M., Lapointe, E., Marcoux, L., Larue, S., Nadeau, A., Chénier, S., Waters, P. J., et al. (2020) · Neurology Genetics · doi:10.1212/nxg.0000000000000408 · Cited by 17 · see citing works
CRISPR/Cas correction of muscular dystrophies
Zhang, Y., Nishiyama, T., Olson, E. N., & Bassel‐Duby, R. (2021) · Experimental Cell Research · doi:10.1016/j.yexcr.2021.112844 · Cited by 17 · see citing works
New Therapeutics Options for Pediatric Neuromuscular Disorders
Flotats‐Bastardas, M., & Hahn, A. (2020) · Frontiers in Pediatrics · doi:10.3389/fped.2020.583877 · Cited by 17 · see citing works
Macdonald, J., Marx, J., & Büning, H. (2021) · Human Gene Therapy · doi:10.1089/hum.2021.169 · Cited by 16 · see citing works
Advanced Gene-Targeting Therapies for Motor Neuron Diseases and Muscular Dystrophies
Chamakioti, M., Karantzelis, N., & Taraviras, S. L. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms23094824 · Cited by 16 · see citing works
Prospect of gene therapy for cardiomyopathy in hereditary muscular dystrophy
Yue, Y., Binalsheikh, I. M., Leach, S. B., Domeier, T. L., & Duan, D. (2015) · Expert Opinion on Orphan Drugs · doi:10.1517/21678707.2016.1124039 · Cited by 15 · see citing works
Bruge, C., Geoffroy, M., Benabidès, M., Pellier, E., Gicquel, E., Dhiab, J., Hoch, L., Richard, I., & Nissan, X. (2022) · Biomedicines · doi:10.3390/biomedicines10061428 · Cited by 15 · see citing works
Baine, S. H., Wier, C., Lemmerman, L. R., Cooper-Olson, G., Kempton, A. N., Haile, A., Endres, J., Fedoce, A., Nesbit, E., Rodino‐Klapac, L. R., et al. (2024) · Human Gene Therapy · doi:10.1089/hum.2024.013 · Cited by 14 · see citing works
Self-citationWu, F., He, W., Xiao, Y., Wu, Q., Zhang, Q., Zhang, T., Xu, L., & Pang, X. (2025) · Advanced Science · doi:10.1002/advs.202408397 · Cited by 12 · see citing works
DNA-Mediated Gene Therapy in a Mouse Model of Limb Girdle Muscular Dystrophy 2B
Ma, J., Pichavant, C., du Bois, H., Bhakta, M. S., & Calos, M. P. (2017) · Molecular Therapy — Methods & Clinical Development · doi:10.1016/j.omtm.2017.10.005 · Cited by 12 · see citing works
Begam, M., Collier, A. F., Mueller, A. L., Roche, R., Galen, S. S., & Roche, J. A. (2018) · Physiological Reports · doi:10.14814/phy2.13727 · Cited by 11 · see citing works
Therapeutic advances in musculoskeletal AAV targeting approaches
Bulaklak, K., & Xiao, X. (2017) · Current Opinion in Pharmacology · doi:10.1016/j.coph.2017.07.001 · Cited by 12 · see citing works
Limb Girdle Muscular Dystrophy Type 2B (LGMD2B): Diagnosis and Therapeutic Possibilities
Poudel, B. H., Fletcher, S., Wilton, S. D., & Aung-Htut, M. T. (2024) · International Journal of Molecular Sciences · doi:10.3390/ijms25115572 · Cited by 11 · see citing works
“A similar preclinical study was performed by Sondergaard and colleagues the dual-vector system to package the DYSF cDNA into AAV serotype rh.74 using discrete vectors with a 1 Kb region of homology [68].”
MethodRescue of lysosomal acid lipase deficiency in mice by rAAV8 liver gene transfer
Laurent, M., Harb, R., Jenny, C., Oustelandt, J., Jimenez, S., Cosette, J., Landini, F., Ferrante, A., Corre, G., Vujić, N., et al. (2025) · Communications Medicine · doi:10.1038/s43856-025-00816-8 · Cited by 13 · see citing works
“TheauthorsusedtherAAVh74serotype,whichhasbeenselectedto transducemuscles 56 – 58 and to treat muscular disorders (Dysferlinopathies: NCT02710500, Duchenne Muscular Dystrophy: NCT02704325, NCT02376816, NCT03375164).”
Advances in Treatments in Muscular Dystrophies and Motor Neuron Disorders
Roy, B., & Griggs, R. C. (2020) · Neurologic Clinics · doi:10.1016/j.ncl.2020.09.005 · Cited by 11 · see citing works
Plasmid-Mediated Gene Therapy in Mouse Models of Limb Girdle Muscular Dystrophy
Guha, T. K., Pichavant, C., & Calos, M. P. (2019) · Molecular Therapy — Methods & Clinical Development · doi:10.1016/j.omtm.2019.10.002 · Cited by 10 · see citing works
“The <5-kb size limit of the vector makes delivery of large genes or combinations of genes difficult.(10,14,15) Furthermore, the immunogenicity of the AAV capsid raises further problems, since a good percentage of the human population possesses pre-existing immunity to AAV, eliminating many patients’ access to AAV-medi…”
BackgroundMethodRational Design of AAV-rh74, AAV3B, and AAV8 with Limited Liver Targeting
Chan, C. T., Harris, K. K., Zolotukhin, S., & Keeler, G. D. (2023) · Viruses · doi:10.3390/v15112168 · Cited by 10 · see citing works
Gene therapy for primary myopathies: literature review and prospects
Querin, G., & Colella, M. (2023) · Archives de Pédiatrie · doi:10.1016/s0929-693x(23)00223-3 · Cited by 8 · see citing works
Антонович, Я. И., Emelin, A. M., Slesarenko, Y. S., Limaev, I. S., Vetrova, I. A., Belikova, L. D., Grafskaia, E. N., Александрович, Б. П., Pokrovsky, M. V., Kuzubova, E. V., et al. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms241713551 · Cited by 7 · see citing works
Dose escalation pre-clinical trial of novel DOK7-AAV in mouse model of DOK7 congenital myasthenia
Cossins, J., Kozma, I., Canzonetta, C., Hawkins, A., Beeson, D., Sepulveda, P. V., & Dong, Y. Y. (2024) · Brain Communications · doi:10.1093/braincomms/fcaf046 · Cited by 5 · see citing works
Targeting Age-Related Neurodegenerative Diseases by AAV-Mediated Gene Therapy
Cagin, U. (2021) · Advances in experimental medicine and biology · doi:10.1007/978-3-030-55035-6_15 · Cited by 5 · see citing works
AAV Vector-Based Gene Therapy, Progress and Current Challenges
Kuranda, K., & Mingozzi, F. (2017) · Springer eBooks · doi:10.1007/978-3-319-53457-2_5 · Cited by 5 · see citing works
Molekulare Therapien: Gegenwart und Zukunft bei neuromuskulären Erkrankungen
Ziegler, A., Walter, M. C., & Schoser, B. E. (2023) · Der Nervenarzt · doi:10.1007/s00115-023-01495-3 · Cited by 5 · see citing works
“Die Verwendung einer dualen Vektorstrategie ermöglicht die Übertragung übergroßer Gene, einschließlich Dysferlin, das 6,9 kb groß ist [36, 49].”
BackgroundPotter, R. A., Griffin, D. A., Heller, K. N., Mendell, J. R., & Rodino‐Klapac, L. R. (2023) · Biology Open · doi:10.1242/bio.059797 · Cited by 4 · see citing works
“Intramuscular delivery was selected to directly compare cassette design using a robust delivery technique with comparable levels of vector genome biodistribution of different constructs (Rodino-Klapac et al., 2010; Sondergaard et al., 2015).”
MethodSelf-citationCurrent Strategies of Muscular Dystrophy Therapeutics: An Overview
Lim, K. R. Q., & Yokota, T. (2022) · Methods in molecular biology · doi:10.1007/978-1-0716-2772-3_1 · Cited by 4 · see citing works
In Vitro Correction of Point Mutations in the DYSF Gene Using Prime Editing
Bouchard, C., Rousseau, J., Lamothe, G., Dubost, M., Bastrenta, L., Ramezani, S., & Tremblay, J. P. (2025) · International Journal of Molecular Sciences · doi:10.3390/ijms26125647 · Cited by 3 · see citing works
Dysferlin and the Regulation of Ca2+ Release in Skeletal Muscle
Bloch, R. J., Muriel, J. M., & Lukyanenko, V. I. (2025) · Cells · doi:10.3390/cells14211724 · Cited by 4 · see citing works
“This approach has been validated in mice [284–287].”
Challenges to Gene Editing Approaches in the Retina
Bonillo, M., Pfromm, J. K., & Fischer, M. D. (2022) · Klinische Monatsblätter für Augenheilkunde · doi:10.1055/a-1757-9810 · Cited by 3 · see citing works
“[34] Sondergaard PC, Griffin DA, Pozsgai ER et al.”
BackgroundThree Novel Immune-deficient Mouse Models of Muscular Dystrophy
Pichavant, C., Bjornson, C. R. R., Gallagher, T., Neal, T. L., du Bois, H., Bhakta, M. S., & Calos, M. P. (2017) · PLoS Currents · doi:10.1371/currents.md.25e9cd5f4740329f2650972a75230188 · Cited by 3 · see citing works
Al‐Moyed, H. (2019) · doi:10.53846/goediss-7430 · Cited by 3 · see citing works
Human β-NGF gene transferred to cat corneal endothelial cells
Luo, W., Liu, M., Zhao, G., Wang, C., Hu, L., & Liu, X. (2016) · International Journal of Ophthalmology · doi:10.18240/ijo.2016.07.01 · Cited by 2 · see citing works
Mendell, J. R., Rodino‐Klapac, L. R., & Shilling, C. J. (2019) · Springer eBooks · doi:10.1007/978-3-030-03095-7_39 · Cited by 2 · see citing works
Self-citationWicklund, M. (2016) · Neurology Genetics · doi:10.1212/nxg.0000000000000092 · Cited by 2 · see citing works
Pool-packaged AAV libraries exhibit extensive length-dependent and homology-dependent chimerism
Lalanne, J., Huynh, C., Mich, J. K., Hunker, A. C., McDiarmid, T. A., Kim, H., Levi, B. P., Ting, J. T., & Shendure, J. (2026) · Nature Biotechnology · doi:10.1038/s41587-026-03097-1 · Cited by 11 · see citing works
Lukyanenko, V. I., Muriel, J. M., Banford, K. K., Kwiatkowski, T. A., Bulgart, H. R., Weisleder, N. L., & Bloch, R. J. (2026) · The Journal of General Physiology · doi:10.1085/jgp.202513844 · Cited by 1 · see citing works
Антонович, Я. И., Chernova, O. N., Олегович, М. М., Limaev, I. S., Александрович, Б. К., Андреевна, Т. А., Аймалетдинов, А. М., Shaimardanova, A. A., Rizvanov, A. A., Bardakov, S. N., et al. (2023) · Bulletin of Experimental Biology and Medicine · doi:10.1007/s10517-023-05789-z · Cited by 1 · see citing works
“3, e), which can be interpreted as an evidence of enhanced reparative rhabdomyohistogenesis and myotube formation [11].”
BackgroundAnalysis of Exon Skipping Applicability for Dysferlinopathies
Leckie, J., Rodriguez, S. H., Krahn, M., & Yokota, T. (2025) · Cells · doi:10.3390/cells14030177 · Cited by 1 · see citing works
Dysferlin in skeletal and heart muscle: from trafficking to therapy
Bersch, K. (2017) · doi:10.53846/goediss-6492 · Cited by 1 · see citing works
Therapeutic Approaches for Dysferlinopathy in Animal Models
Lostal, W., & Richard, I. (2019) · Springer eBooks · doi:10.1007/978-3-030-03095-7_25 · Cited by 1 · see citing works
[Sudden death of a 22-month-old infant due to hyperglycemic accident].
Cau, G., Yacoub, M., Faure, H., & Faure, J. (1968) · PubMed
Molecular Genetic Therapies in the Muscular Dystrophies
Nicolau, S., & Flanigan, K. M. (2023) · Current clinical neurology · doi:10.1007/978-3-031-44009-0_18
Bruge, C., Bourg, N., Pellier, E., Miagoux, Q., Benabidès, M., Grossi, N., Jarrige, M., Polvèche, H., Agostini, V., Brureau, A., et al. (2025) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2025.09.11.675589
DAB2 in LGMD R2: a molecular link between disease progression and lipid dysregulation
Bruge, C., Bourg, N., Pellier, E., Miagoux, Q., Benabidès, M., Grossi, N., Hayat, H., Jarrige, M., Polvèche, H., Agostini, V., et al. (2026) · JCI Insight · doi:10.1172/jci.insight.200054
Bioinformatics tools for the systems biology of dysferlin deficiency
Malatras, A. (2017) · theses.fr (ABES) · doi:10.70675/8817b812z4587z474bzae68ze8e5dfc7ade1
CRISPR-Cas-Based Editing Technologies in Preclinical Models for Disease Correction
Karki, P., & Sudarshan, G. C. (2026) · Genetics. · doi:10.5772/intechopen.1015771
Gene therapy in limb-girdle muscular dystrophy (LGMD)
Roudsari, Z. O., & Niazi, P. (2026) · Elsevier eBooks · doi:10.1016/b978-0-443-40467-2.00013-0
McCormack, N. M., Lee-Diaz, S., Reyes, T. R., Hogarth, M. W., Covington, J. L., Bragg, C. A., Harper, Z. O., Diehn, T., Novak, J. S., Halbert, C. L., et al. (2026) · Science Translational Medicine · doi:10.1126/scitranslmed.aei5938
- Authors
- Sondergaard, P. C., Griffin, D. A., Pozsgai, E. R., Johnson, R. W., Grose, W. E., Heller, K. N., Shontz, K. M., Montgomery, C. L., Liu, J., Clark, K. R., Sahenk, Z., Mendell, J. R., & Rodino‐Klapac, L. R.
- Affiliations
- Nationwide Children's Hospital (US)
- Corresponding author
- Rodino‐Klapac, Louise R.
- Venue
- Annals of Clinical and Translational Neurology
- Publisher
- Wiley
- Published
- 2015-01-20
- Volume
- 2
- Issue
- 3
- Pages
- 256-270
- ISSN
- 2328-9503 (ISSN-L)
- PMC
- PMC4369275
- OpenAlex
- W2091504719
- Cited by
- 99
- References
- 57
- Citations by year
- 2026: 6 · 2025: 8 · 2024: 8 · 2023: 11 · 2022: 5 · 2021: 10 · 2020: 7 · 2019: 9 · 2018: 5 · 2017: 18 · 2016: 7 · 2015: 4
- FWCI
- 7.79
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Annals of Clinical and Translational Neurology (publishedVersion, cc-by-nc-nd)
- Europe PMC (PubMed Central) (publishedVersion, cc-by-nc-nd)
- PubMed Central (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- Funders
- Jain Foundation (932013)
- Nationwide Children's Hospital
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Virus-based gene therapy research
- Health Sciences › Medicine › Genetics › Neurogenetic and Muscular Disorders Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Muscle Physiology and Disorders
- Keywords
- dysferlinopathy, dysferlin, adeno-associated virus vectors, muscular dystrophy, muscle regeneration, membrane repair, non-human primates, gene therapy safety, muscle fiber loss
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
