Iorio A, Stonebraker JS, Chambost H, Makris M, Coffin D, Herr C, et al. Establishing the prevalence and prevalence at birth of hemophilia in males: A meta-analytic approach using national registries. Ann Intern Med. 2019;171:540–6.
Google Scholar
Mazepa MA, Monahan PE, Baker JR, Riske BK, Soucie JM, Network USHTC. Men with severe hemophilia in the United States: birth cohort analysis of a large national database. Blood. 2016;127:3073–81.
Google Scholar
Srivastava A, Santagostino E, Dougall A, Kitchen S, Sutherland M, Pipe SW, et al. WFH guidelines for the management of hemophilia, 3rd edition. Haemophilia. 2020;26:1–158.
Google Scholar
Bunting S, Zhang L, Xie L, Bullens S, Mahimkar R, Fong S, et al. Gene therapy with BMN 270 results in therapeutic levels of FVIII in mice and primates and normalization of bleeding in hemophilic mice. Mol Ther. 2018;26:496–509.
Google Scholar
Pasi KJ, Laffan M, Rangarajan S, Robinson TM, Mitchell N, Lester W, et al. Persistence of haemostatic response following gene therapy with valoctocogene roxaparvovec in severe haemophilia A. Haemophilia. 2021;27:947–56.
Google Scholar
Rangarajan S, Walsh L, Lester W, Perry D, Madan B, Laffan M, et al. AAV5-Factor VIII gene transfer in severe hemophilia A. N Engl J Med. 2017;377:2519–30.
Google Scholar
Pasi KJ, Rangarajan S, Mitchell N, Lester W, Symington E, Madan B, et al. Multiyear follow-up of AAV5-hFVIII-SQ gene therapy for hemophilia A. N Engl J Med. 2020;382:29–40.
Google Scholar
Han S, Park S-J, Yoo G, Kim J-Y, Lee S, Hwang J, et al. Biodistribution and shedding studies of adeno-associated virus 5 in C57BL/6 mice by quantitative PCR. Mol Ther. 2018;26:190.
Rajasekaran S, Thatte J, Periasamy J, Javali A, Jayaram M, Sen D, et al. Infectivity of adeno-associated virus serotypes in mouse testis. BMC Biotechnol. 2018;18:70.
Google Scholar
Ferla R, Marteau J-B, Pouillot S, Kozarsky K, Brown J, Galimberti S, et al. GLP-compliant non-clinical safety and biodistribution of a recombinant AAV2/8 vector administered intravenously for treatment of mucopolysaccharidosis type VI. Mol Ther. 2016;24:S185.
Google Scholar
Ferla R, Alliegro M, Marteau JB, Dell’Anno M, Nusco E, Pouillot S, et al. Non-clinical safety and efficacy of an AAV2/8 vector administered intravenously for treatment of mucopolysaccharidosis type VI. Mol Ther Methods Clin Dev. 2017;6:143–58.
Google Scholar
Favaro P, Finn JD, Siner JI, Wright JF, High KA, Arruda VR. Safety of liver gene transfer following peripheral intravascular delivery of adeno-associated virus (AAV)-5 and AAV-6 in a large animal model. Hum Gene Ther. 2011;22:843–52.
Google Scholar
Ware T, Murrey D, McCarty D, Fu H. Normalized survival and permanent restoration of NAGLU activity in the CNS, PNS and somatic tissues in MPS IIIB mice after a single intravenous rAAV9-hNAGLU gene delivery. Mol Ther. 2012;20:S13.
Mattar CN, Nathwani A, Waddington S, Dighe N, Kaeppel C, Nowrouzi A, et al. Outcomes of AAV8 and AAV5-mediated fetal gene transfer at 0.9g in non-human primates. Mol Ther. 2011;19:S18.
Google Scholar
Schuettrumpf J, Liu JH, Couto LB, Addya K, Leonard DG, Zhen Z, et al. Inadvertent germline transmission of AAV2 vector: findings in a rabbit model correlate with those in a human clinical trial. Mol Ther. 2006;13:1064–73.
Google Scholar
Pachori AS, Melo LG, Zhang L, Loda M, Pratt RE, Dzau VJ. Potential for germ line transmission after intramyocardial gene delivery by adeno-associated virus. Biochem Biophys Res Commun. 2004;313:528–33.
Google Scholar
Arruda VR, Fields PA, Milner R, Wainwright L, De Miguel MP, Donovan PJ, et al. Lack of germline transmission of vector sequences following systemic administration of recombinant AAV-2 vector in males. Mol Ther. 2001;4:586–92.
Google Scholar
Shinkai Y, Rathbun G, Lam KP, Oltz EM, Stewart V, Mendelsohn M, et al. RAG-2-deficient mice lack mature lymphocytes owing to inability to initiate V(D)J rearrangement. Cell. 1992;68:855–67.
Google Scholar
Oakberg EF. Duration of spermatogenesis in the mouse and timing of stages of the cycle of the seminiferous epithelium. Am J Anat. 1956;99:507–16.
Google Scholar
Dadoune JP, Alfonsi MF. Autoradiographic investigation of sperm transit through the male mouse genital tract after tritiated thymidine incorporation. Reprod Nutr Dev. 1984;24:927–35.
Google Scholar
Gervasi MG, Visconti PE. Molecular changes and signaling events occurring in spermatozoa during epididymal maturation. Andrology. 2017;5:204–18.
Google Scholar
National Research Council (US). Committee for the update of the guide for the care and use of laboratory animals. guide for the care and use of laboratory animals. 8th ed. National Academies Press (US): Washington (DC); 2011.
Couto L, Parker A, Gordon JW. Direct exposure of mouse spermatozoa to very high concentrations of a serotype-2 adeno-associated virus gene therapy vector fails to lead to germ cell transduction. Hum Gene Ther. 2004;15:287–91.
Google Scholar
Royo A, González-Aseguinolaza G, Aizpun I, Rodríguez A, Cornet M, del Mar Municio M et al. No longitudinal transmission of AAV5-PBGD vector DNA in mice. Toxicol Lett. 2013;221:S213–14.
Jakob M, Muhle C, Park J, Weiss S, Waddington S, Schneider H. No evidence for germ-line transmission following prenatal and early postnatal AAV-mediated gene delivery. J Gene Med. 2005;7:630–7.
Google Scholar
Niemeyer GP, Herzog RW, Mount J, Arruda VR, Tillson DM, Hathcock J, et al. Long-term correction of inhibitor-prone hemophilia B dogs treated with liver-directed AAV2-mediated factor IX gene therapy. Blood. 2009;113:797–806.
Google Scholar
Chandler RJ, Sands MS, Venditti CP. Recombinant adeno-associated viral integration and genotoxicity: insights from animal models. Hum Gene Ther. 2017;28:314–22.
Google Scholar
Nakai H, Montini E, Fuess S, Storm TA, Grompe M, Kay MA. AAV serotype 2 vectors preferentially integrate into active genes in mice. Nat Genet. 2003;34:297–302.
Google Scholar
Nakai H, Wu X, Fuess S, Storm TA, Munroe D, Montini E, et al. Large-scale molecular characterization of adeno-associated virus vector integration in mouse liver. J Virol. 2005;79:3606–14.
Google Scholar
Nguyen GN, Everett JK, Kafle S, Roche AM, Raymond HE, Leiby J, et al. A long-term study of AAV gene therapy in dogs with hemophilia A identifies clonal expansions of transduced liver cells. Nat Biotechnol. 2021;39:47–55.
Google Scholar
Kazazian HH Jr. An estimated frequency of endogenous insertional mutations in humans. Nat Genet. 1999;22:130.
Google Scholar
Afione SA, Conrad CK, Kearns WG, Chunduru S, Adams R, Reynolds TC, et al. In vivo model of adeno-associated virus vector persistence and rescue. J Virol. 1996;70:3235–41.
Google Scholar
Duan D, Sharma P, Yang J, Yue Y, Dudus L, Zhang Y, et al. Circular intermediates of recombinant adeno-associated virus have defined structural characteristics responsible for long-term episomal persistence in muscle tissue. J Virol. 1998;72:8568–77.
Google Scholar
Vincent-Lacaze N, Snyder RO, Gluzman R, Bohl D, Lagarde C, Danos O. Structure of adeno-associated virus vector DNA following transduction of the skeletal muscle. J Virol. 1999;73:1949–55.
Google Scholar
Nakai H, Storm TA, Kay MA. Recruitment of single-stranded recombinant adeno-associated virus vector genomes and intermolecular recombination are responsible for stable transduction of liver in vivo. J Virol. 2000;74:9451–63.
Google Scholar
Nakai H, Yant SR, Storm TA, Fuess S, Meuse L, Kay MA. Extrachromosomal recombinant adeno-associated virus vector genomes are primarily responsible for stable liver transduction in vivo. J Virol. 2001;75:6969–76.
Google Scholar
Song S, Laipis PJ, Berns KI, Flotte TR. Effect of DNA-dependent protein kinase on the molecular fate of the rAAV2 genome in skeletal muscle. Proc Natl Acad Sci U S A. 2001;98:4084–8.
Google Scholar
Nakai H, Thomas CE, Storm TA, Fuess S, Powell S, Wright JF, et al. A limited number of transducible hepatocytes restricts a wide-range linear vector dose response in recombinant adeno-associated virus-mediated liver transduction. J Virol. 2002;76:11343–9.
Google Scholar
Song S, Lu Y, Choi YK, Han Y, Tang Q, Zhao G, et al. DNA-dependent PK inhibits adeno-associated virus DNA integration. Proc Natl Acad Sci U S A. 2004;101:2112–6.
Google Scholar
Penaud-Budloo M, Le Guiner C, Nowrouzi A, Toromanoff A, Cherel Y, Chenuaud P, et al. Adeno-associated virus vector genomes persist as episomal chromatin in primate muscle. J Virol. 2008;82:7875–85.
Google Scholar
McIntosh J, Lenting PJ, Rosales C, Lee D, Rabbanian S, Raj D, et al. Therapeutic levels of FVIII following a single peripheral vein administration of rAAV vector encoding a novel human factor VIII variant. Blood. 2013;121:3335–44.
Google Scholar

