Nathwani AC, Tuddenham EG, Rangarajan S, Rosales C, McIntosh J, Linch DC, et al. Adenovirus-associated virus vector-mediated gene transfer in hemophilia B. N Engl J Med. 2011;365:2357–65.

Article  PubMed  PubMed Central  CAS  Google Scholar 

Manno CS, Pierce GF, Arruda VR, Glader B, Ragni M, Rasko JJ, et al. Successful transduction of liver in hemophilia by AAV-Factor IX and limitations imposed by the host immune response. Nat Med. 2006;12:342–7.

Article  PubMed  CAS  Google Scholar 

Nathwani AC, Rosales C, McIntosh J, Rastegarlari G, Nathwani D, Raj D, et al. Long-term safety and efficacy following systemic administration of a self-complementary AAV vector encoding human FIX pseudotyped with serotype 5 and 8 capsid proteins. Mol Ther. 2011;19:876–85.

Article  PubMed  PubMed Central  CAS  Google Scholar 

Foust KD, Wang X, McGovern VL, Braun L, Bevan AK, Haidet AM, et al. Rescue of the spinal muscular atrophy phenotype in a mouse model by early postnatal delivery of SMN. Nat Biotechnol. 2010;28:271–4.

Article  PubMed  PubMed Central  CAS  Google Scholar 

Fu H, Dirosario J, Killedar S, Zaraspe K, McCarty DM. Correction of neurological disease of mucopolysaccharidosis IIIB in adult mice by rAAV9 trans-blood-brain barrier gene delivery. Mol Ther. 2011;19:1025–33.

Article  PubMed  PubMed Central  CAS  Google Scholar 

Ruzo A, Marco S, Garcia M, Villacampa P, Ribera A, Ayuso E, et al. Correction of Pathological Accumulation of Glycosaminoglycans in Central Nervous System and Peripheral Tissues of MPSIIIA Mice Through Systemic AAV9 Gene Transfer. Hum Gene Ther. 2012;23:1237–46.

Article  PubMed  CAS  Google Scholar 

Foust KD, Nurre E, Montgomery CL, Hernandez A, Chan CM, Kaspar BK. Intravascular AAV9 preferentially targets neonatal neurons and adult astrocytes. Nat Biotechnol. 2009;27:59–65.

Article  PubMed  CAS  Google Scholar 

Duque S, Joussemet B, Riviere C, Marais T, Dubreil L, Douar AM, et al. Intravenous administration of self-complementary AAV9 enables transgene delivery to adult motor neurons. Mol Ther. 2009;17:1187–96.

Article  PubMed  PubMed Central  CAS  Google Scholar 

Fu H, Cataldi MP, Ware TA, Zaraspe K, Meadows AS, Murrey DA, et al. Functional correction of neurological and somatic disorders at later stages of disease in MPS IIIA mice by systemic scAAV9-hSGSH gene delivery. Mol Ther Methods Clin Dev. 2016;3:16036.

Article  PubMed  PubMed Central  CAS  Google Scholar 

Bailey RM, Armao D, Nagabhushan Kalburgi S, Gray SJ. Development of Intrathecal AAV9 Gene Therapy for Giant Axonal Neuropathy. Mol Ther Methods Clin Dev. 2018;9:160–71.

Article  PubMed  PubMed Central  CAS  Google Scholar 

Boutin S, Monteilhet V, Veron P, Leborgne C, Benveniste O, Montus MF, et al. Prevalence of serum IgG and neutralizing factors against adeno-associated virus (AAV) types 1, 2, 5, 6, 8, and 9 in the healthy population: implications for gene therapy using AAV vectors. Hum Gene Ther. 2010;21:704–12.

Article  PubMed  CAS  Google Scholar 

Calcedo R, Vandenberghe LH, Gao G, Lin J, Wilson JM. Worldwide epidemiology of neutralizing antibodies to adeno-associated viruses. J Infect Dis. 2009;199:381–90.

Article  PubMed  Google Scholar 

Fu H, Meadows AS, Pineda RJ, Kunkler KL, Truxal KV, McBride KL, et al. Differential Prevalence of Antibodies Against Adeno-Associated Virus in Healthy Children and Patients with Mucopolysaccharidosis III: Perspective for AAV-Mediated Gene Therapy. Human Gene Ther Clin Dev. 2017;28:187–96.

Article  CAS  Google Scholar 

Scallan CD, Jiang H, Liu T, Patarroyo-White S, Sommer JM, Zhou S, et al. Human immunoglobulin inhibits liver transduction by AAV vectors at low AAV2 neutralizing titers in SCID mice. Blood. 2006;107:1810–7.

Article  PubMed  CAS  Google Scholar 

Wang L, Calcedo R, Bell P, Lin J, Grant RL, Siegel DL, et al. Impact of pre-existing immunity on gene transfer to nonhuman primate liver with adeno-associated virus 8 vectors. Human Gene Ther. 2011;22:1389–401.

Article  CAS  Google Scholar 

McIntosh JH, Cochrane M, Cobbold S, Waldmann H, Nathwani SA, Davidoff AM, et al. Successful attenuation of humoral immunity to viral capsid and transgenic protein following AAV-mediated gene transfer with a non-depleting CD4 antibody and cyclosporine. Gene Ther. 2012;19:78–85.

Article  PubMed  CAS  Google Scholar 

Mingozzi F, Chen Y, Murphy SL, Edmonson SC, Tai A, Price SD, et al. Pharmacological modulation of humoral immunity in a nonhuman primate model of AAV gene transfer for hemophilia B. Mol Ther. 2012;20:1410–6.

Article  PubMed  PubMed Central  CAS  Google Scholar 

Corti M, Elder M, Falk D, Lawson L, Smith B, Nayak S, et al. B-Cell Depletion is Protective Against Anti-AAV Capsid Immune Response: A Human Subject Case Study. Mol Ther Method Clin Dev. 2014;1:14033.

Article  CAS  Google Scholar 

Chicoine LG, Montgomery CL, Bremer WG, Shontz KM, Griffin DA, Heller KN, et al. Plasmapheresis eliminates the negative impact of AAV antibodies on microdystrophin gene expression following vascular delivery. Mol Ther. 2014;22:338–47.

Article  PubMed  CAS  Google Scholar 

Chicoine LG, Rodino-Klapac LR, Shao G, Xu R, Bremer WG, Camboni M, 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;22:713–24.

Article  PubMed  PubMed Central  CAS  Google Scholar 

Velazquez VM, Meadows AS, Pineda RJ, Camboni M, McCarty DM, Fu H. Effective Depletion of Pre-existing Anti-AAV Antibodies Requires Broad Immune Targeting. Mol Ther Methods Clin Dev. 2017;4:159–68.

Article  PubMed  PubMed Central  CAS  Google Scholar 

Mingozzi F, Anguela XM, Pavani G, Chen Y, Davidson RJ, Hui DJ, et al. Overcoming preexisting humoral immunity to AAV using capsid decoys. Sci Transl Med. 2013;5:194ra92.

Article  PubMed  PubMed Central  CAS  Google Scholar 

Maersch S, Huber A, Buning H, Hallek M, Perabo L. Optimization of stealth adeno-associated virus vectors by randomization of immunogenic epitopes. Virology. 2010;397:167–75.

Article  PubMed  CAS  Google Scholar 

Asokan A, Samulski RJ. AAV does the shuffle. Nat Biotechnol. 2006;24:158–60.

Article  PubMed  CAS  Google Scholar 

Lee GK, Maheshri N, Kaspar B, Schaffer DV. PEG conjugation moderately protects adeno-associated viral vectors against antibody neutralization. Biotechnol Bioeng. 2005;92:24–34.

Article  PubMed  CAS  Google Scholar 

Monteilhet V, Saheb S, Boutin S, Leborgne C, Veron P, Montus MF, et al. A 10 patient case report on the impact of plasmapheresis upon neutralizing factors against adeno-associated virus (AAV) types 1, 2, 6, and 8. Mol Ther. 2011;19:2084–91.

Article  PubMed  PubMed Central  CAS  Google Scholar 

Unzu C, Hervas-Stubbs S, Sampedro A, Mauleon I, Mancheno U, Alfaro C, et al. Transient and intensive pharmacological immunosuppression fails to improve AAV-based liver gene transfer in non-human primates. J Transl Med. 2012;10:122.

Article  PubMed  PubMed Central  CAS  Google Scholar 

Leborgne C, Barbon E, Alexander JM, Hanby H, Delignat S, Cohen DM, et al. IgG-cleaving endopeptidase enables in vivo gene therapy in the presence of anti-AAV neutralizing antibodies. Nat Med. 2020;26:1096–101.

Article  PubMed  CAS  Google Scholar 

Elmore ZC, Oh DK, Simon KE, Fanous MM, Asokan A Rescuing AAV gene transfer from neutralizing antibodies with an IgG-degrading enzyme. JCI Insight. 2020;5.

von Pawel-Rammingen U, Johansson BP, Bjorck L. IdeS, a novel streptococcal cysteine proteinase with unique specificity for immunoglobulin G. EMBO J. 2002;21:1607–15.

Article  Google Scholar 

Vincents B, von Pawel-Rammingen U, Bjorck L, Abrahamson M. Enzymatic characterization of the streptococcal endopeptidase, IdeS, reveals that it is a cysteine protease with strict specificity for IgG cleavage due to exosite binding. Biochemistry. 2004;43:15540–9.

Article  PubMed  CAS  Google Scholar 

Wenig K, Chatwell L, von Pawel-Rammingen U, Bjorck L, Huber R, Sondermann P. Structure of the streptococcal endopeptidase IdeS, a cysteine proteinase with strict specificity for IgG. Proc Natl Acad Sci USA. 2004;101:17371–6.

Article  PubMed  PubMed Central  CAS  Google Scholar 

Johansson BP, Shannon O, Bjorck L. IdeS: a bacterial proteolytic enzyme with therapeutic potential. PLoS ONE. 2008;3:e1692.

Article  PubMed  PubMed Central  CAS  Google Scholar 

Ryan MH, Petrone D, Nemeth JF, Barnathan E, Bjorck L, Jordan RE. Proteolysis of purified IgGs by human and bacterial enzymes in vitro and the detection of specific proteolytic fragments of endogenous IgG in rheumatoid synovial fluid. Mol Immunol. 2008;45:1837–46.

Article  PubMed  CAS  Google Scholar 

von Pawel-Rammingen U, Johansson BP, Tapper H, Bjorck L. Streptococcus pyogenes and phagocytic killing. Nat Med. 2002;8:1044–5.

Article  CAS