Restricted accessResearch articleFirst published online 2026-2
Preclinical Assessment of Antibody Responses to Adeno-Associated Virus (AAV) Vector-Based Capsids of AAV2,AAV5,AAV8,or AAV9 in Laboratory Cynomolgus Macaques ( Macaca fascicularis ) of Asian or Mauritian Origin
Adeno-associated virus (AAV)-based vectors are the most commonly used vectors for gene therapy. Wild-type AAV infections occur widely in humans and nonhuman primates (NHPs), and an accurate assessment of preexisting AAV antibodies is crucial for the efficient use of AAV-based gene therapies in preclinical and clinical studies. Cynomolgus macaques (Macaca fascicularis) are well-established preclinical large animal models for evaluating the efficacy and safety of AAV-mediated gene therapies intended for human use. We provide a retrospective evaluation comparing preexisting AAV-neutralizing or total antibody titers against serotypes AAV2, AAV5, AAV8, or AAV9 in cynomolgus macaque cohorts of Asian or Mauritian origin. We used an in vitro neutralizing antibody (NAB) assay to detect NAB titers or an in vitro Meso Scale Discovery-based assay for the quantification of total binding antibodies (TABs) in blood samples. Results were obtained to measure the serostatus of animals. In our analysis, the in vitro NAB assay revealed the lowest seroprevalence for AAV5 (13 ± 15% to 21 ± 6%) independent of origin. In the same assay, Asian animals were highly seropositive against AAV8, followed by AAV2 and AAV9 serotypes (88 ± 13%, 71 ± 10%, 69 ± 9%, respectively). Whereby, the prevalence of seropositivity was lower in animals of Mauritian origin with the highest seroprevalence for AAV9 (58 ± 7%), followed by AAV8 (53 ± 17%) and AAV2 (51 ± 20%) assessed by in vitro TAB assay. Notably, co-prevalences of antibody responses against AAV2, AAV8, and AAV9 serotypes resulted in 39.8% seropositivity (in vitro NAB assay) in NHPs of Asian and in about 32.6% (in vitro TAB assay) of Mauritian origin.
Coura RdosS, NardiNB. The state of the art of adeno-associated virus-based vectors in gene therapy. Virol J, 2007; 4(99):99; doi: 10.1186/1743-422X-4-99
2.
WangD, TaiPWL, GaoG. Adeno-associated virus vector as a platform for gene therapy delivery. Nat Rev Drug Discov, 2019; 18(5):358–378; doi: 10.1038/s41573-019-0012-9
KingAM, AdamsMJ, CarstensEB, et al.Virus Taxonomy: Ninth Report of the International Committee on Taxonomy of Viruses. Elsevier Academic Press: 2011.
5.
SrivastavaA. In vivo tissue-tropism of adeno-associated viral vectors. Curr Opin Virol, 2016; 21:75–80; doi: 10.1016/j.coviro.2016.08.003
6.
PupoA, FernandezA, LowSH, et al.AAV vectors: The Rubik’s cube of human gene therapy. Mol Ther, 2022; 30(12):3515–3541; doi: 10.1016/j.ymthe.2022.09.015
7.
HüserD, KhalidD, LutterT, et al.High prevalence of infectious adeno-associated virus (AAV) in human peripheral blood mononuclear cells indicative of T lymphocytes as sites of AAV persistence. J Virol, 2017; 91(4):e02137–e02116; doi: 10.1128/JVI.02137-16
8.
BalakrishnanB, JayandharanGR. Basic biology of adeno-associated virus (AAV) vectors used in gene therapy. Curr Gene Ther, 2014; 14(2):86–100; doi: 10.2174/1566523214666140302193709
FDA. FDA approves novel gene therapy to treat patients with a rare form of inherited vision loss. Press Release, 2017.
11.
DucloyerJB, Le MeurG, CroninT, et al.La thérapie génique des rétinites pigmentaires héréditaires [Gene therapy for retinitis pigmentosa]. Med Sci (Paris), 2020; 36(6–7):607–615; doi: 10.1051/medsci/2020095
12.
RodriguesGA, ShalaevE, KaramiTK, et al.Pharmaceutical development of AAV-based gene therapy products for the eye. Pharm Res, 2018; 36(2):29; doi: 10.1007/s11095-018-2554-7
13.
UrquhartL. FDA new drug approvals in Q2 2019. Nat Rev Drug Discov, 2019; 18(8):575; doi: 10.1038/d41573-019-00121-9
14.
MendellJR, Al-ZaidyS, ShellR, et al.Single-dose gene-replacement therapy for spinal muscular atrophy. N Engl J Med, 2017; 377(18):1713–1722; doi: 10.1056/NEJMoa1706198
15.
MietzschM, NelsonAR, HsiJ, et al.Structural characterization of antibody-responses from Zolgensma treatment provides the blueprint for the engineering of an AAV capsid suitable for redosing. bioRxiv, 2024; doi: 10.1101/2024.05.01.590489
16.
MullardA. FDA approves first haemophilia B gene therapy. Nat Rev Drug Discov, 2023; 22(1):7; doi: 10.1038/d41573-022-00199-8
17.
PipeSW, LeebeekFWG, RechtM, et al.Gene therapy with etranacogene dezaparvovec for hemophilia B. N Engl J Med, 2023; 388(8):706–718; doi: 10.1056/NEJMoa2211644
18.
MullardA. FDA approves first gene therapy for Duchenne muscular dystrophy, despite internal objections. Nat Rev Drug Discov, 2023; 22(8):610; doi: 10.1038/d41573-023-00103-y
WangL, CalcedoR, WangH, et al.The pleiotropic effects of natural AAV infections on liver-directed gene transfer in macaques. Mol Ther, 2010; 18(1):126–134; doi: 10.1038/mt.2009.245
21.
MingozziF, HighKA. Overcoming the host immune response to adeno-associated virus gene delivery vectors: The race between clearance, tolerance, neutralization, and escape. Annu Rev Virol, 2017; 4(1):511–534; doi: 10.1146/annurev-virology-101416-041936
22.
CalcedoR, ChichesterJA, WilsonJM. Assessment of humoral, innate, and T-cell immune responses to adeno-associated virus vectors. Hum Gene Ther Methods, 2018; 29(2):86–95; doi: 10.1089/hgtb.2018.038
23.
FaleseL, SandzaK, YatesB, et al.Strategy to detect pre-existing immunity to AAV gene therapy. Gene Ther, 2017; 24(12):768–778; doi: 10.1038/gt.2017.95
24.
HaarJ, BlazevicD, StrobelB, et al.MSD-based assays facilitate a rapid and quantitative serostatus profiling for the presence of anti-AAV antibodies. Mol Ther Methods Clin Dev, 2022; 25:360–369; doi: 10.1016/j.omtm.2022.04.008
25.
KottermanMA, YinL, StrazzeriJM, et al.Antibody neutralization poses a barrier to intravitreal adeno-associated viral vector gene delivery to non-human primates. Gene Ther, 2015; 22(2):116–126; doi: 10.1038/gt.2014.115
26.
DhungelBP, WinburnI, PereiraCDF, et al.Understanding AAV vector immunogenicity: From particle to patient. Theranostics, 2024; 14(3):1260–1288; doi: 10.7150/thno.89380
27.
AssafBT, WhiteleyLO. Considerations for preclinical safety assessment of adeno-associated virus gene therapy products. Toxicol Pathol, 2018; 46(8):1020–1027; doi: 10.1177/0192623318803867
28.
MendellJR, ProudC, ZaidmanCM, et al.Practical considerations for delandistrogene moxeparvovec gene therapy in patients with Duchenne muscular dystrophy. Pediatr Neurol, 2024; 153:11–18; doi: 10.1016/j.pediatrneurol.2024.01.003
29.
BaldrickP, McIntoshB, PrasadM. Adeno-associated virus (AAV)-based gene therapy products: What are toxicity studies in non-human primates showing us? Regul Toxicol Pharmacol, 2023; 138:105332; doi: 10.1016/j.yrtph.2022.105332
30.
MartinPL, WeinbauerGF. Developmental toxicity testing of biopharmaceuticals in nonhuman primates: Previous experience and future directions. Int J Toxicol, 2010; 29(6):552–568; doi: 10.1177/1091581810378896
31.
Grote-WesselsS, FringsW, SmithCA, et al.Immunotoxicity testing in nonhuman primates. Methods Mol Biol, 2010; 598:341–359; doi: 10.1007/978-1-60761-401-2_23
32.
NakamuraT, FujiwaraK, SaitouM, et al.Non-human primates as a model for human development. Stem Cell Reports, 2021; 16(5):1093–1103; doi: 10.1016/j.stemcr.2021.03.021
33.
ColmanK. Impact of the genetics and source of preclinical safety animal models on study design, results, and interpretation. Toxicol Pathol, 2017; 45(1):94–106; doi: 10.1177/0192623316672743
34.
ArndtT, MeindelM, ClarkeJ, et al.Comparison of routine hematology, coagulation, and clinical chemistry parameters of cynomolgus macaques of Mauritius origin with cynomolgus macaques of Cambodia, China, and Vietnam origin. Toxicol Pathol, 2022; 50(5):591–606; doi: 10.1177/01926233221089843
35.
MajowiczA, NijmeijerB, LampenMH, et al.Therapeutic hFIX activity achieved after single AAV5-hFIX treatment in hemophilia B patients and NHPs with pre-existing anti-AAV5 NABs. Mol Ther Methods Clin Dev, 2019; 14:27–36; doi: 10.1016/j.omtm.2019.05.009
36.
JiangH, CoutoLB, Patarroyo-WhiteS, et al.Effects of transient immunosuppression on adenoassociated, virus-mediated, liver-directed gene transfer in rhesus macaques and implications for human gene therapy. Blood, 2006; 108(10):3321–3328; doi: 10.1182/blood-2006-04-017913
37.
MannoCS, PierceGF, ArrudaVR, et al.Successful transduction of liver in hemophilia by AAV-Factor IX and limitations imposed by the host immune response. Nat Med, 2006; 12(3):342–347; doi: 10.1038/nm1358
38.
HurlbutGD, ZieglerRJ, NietupskiJB, et al.Preexisting immunity and low expression in primates highlight translational challenges for liver-directed AAV8-mediated gene therapy. Mol Ther, 2010; 18(11):1983–1994; doi: 10.1038/mt.2010.175
39.
PedenCS, BurgerC, MuzyczkaN, et al.Circulating anti-wild-type adeno-associated virus type 2 (AAV2) antibodies inhibit recombinant AAV2 (rAAV2)-mediated, but not rAAV5-mediated, gene transfer in the brain. J Virol, 2004; 78(12):6344–6359; doi: 10.1128/JVI.78.12.6344-6359.2004
40.
WangL, CalcedoR, BellP, et al.Impact of pre-existing immunity on gene transfer to nonhuman primate liver with adeno-associated virus 8 vectors. Hum Gene Ther, 2011; 22(11):1389–1401; doi: 10.1089/hum.2011.031
41.
WesthausA, Cabanes-CreusM, DilworthKL, et al.Assessment of pre-clinical liver models based on their ability to predict the liver-tropism of adeno-associated virus vectors. Hum Gene Ther, 2023; 34(7–8):273–288; doi: 10.1089/hum.2022.188
42.
CalcedoR, MorizonoH, WangL, et al.Adeno-associated virus antibody profiles in newborns, children, and adolescents. Clin Vaccine Immunol, 2011; 18(9):1586–1588; doi: 10.1128/CVI.05107-11
43.
Navarro-OliverosM, VidaurrazagaA, Soares GuerraG, et al.Seroprevalence of adeno-associated virus types 1, 2, 3, 4, 5, 6, 8, and 9 in a Basque cohort of healthy donors. Sci Rep, 2024; 14(1):15941; doi: 10.1038/s41598-024-66546-4
44.
ZygmuntDA, CroweKE, FlaniganKM, et al.Comparison of serum rAAV serotype-specific antibodies in patients with Duchenne muscular dystrophy, Becker muscular dystrophy, inclusion body myositis, or GNE myopathy. Hum Gene Ther, 2017; 28(9):737–746; doi: 10.1089/hum.2016.141
45.
KashiwakuraY, BaatartsogtN, YamazakiS, et al.The seroprevalence of neutralizing antibodies against the adeno-associated virus capsids in Japanese hemophiliacs. Mol Ther Methods Clin Dev, 2022; 27:404–414; doi: 10.1016/j.omtm.2022.10.014
46.
LiC, NarkbunnamN, SamulskiRJ, et al.; Joint Outcome Study Investigators. Neutralizing antibodies against adeno-associated virus examined prospectively in pediatric patients with hemophilia. Gene Ther, 2012; 19(3):288–294; doi: 10.1038/gt.2011.90
47.
LeborgneC, LatournerieV, BoutinS, et al.Prevalence and long-term monitoring of humoral immunity against adeno-associated virus in Duchenne muscular dystrophy patients. Cell Immunol, 2019; 342:103780; doi: 10.1016/j.cellimm.2018.03.004
48.
VermaS, NwosuSN, RazdanR, et al.Seroprevalence of adeno-associated virus neutralizing antibodies in males with Duchenne muscular dystrophy. Hum Gene Ther, 2023; 34(9–10):430–438; doi: 10.1089/hum.2022.081
49.
CalcedoR, VandenbergheLH, GaoG, et al.Worldwide epidemiology of neutralizing antibodies to adeno-associated viruses. J Infect Dis, 2009; 199(3):381–390; doi: 10.1086/595830
50.
BoutinS, MonteilhetV, VeronP, 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(6):704–712; doi: 10.1089/hum.2009.182
51.
YagiH, MizukamiH, TsukaharaT, et al.Prevalence of neutralizing antibodies against adeno-associated virus 2, 8 and 9 in non-human primate colonies. Molecular Therapy, 2010; 18(1):S214; doi: 10.1016/S1525-0016(16)37995-3
52.
KhatriA, ShelkeR, GuanS, et al.Higher seroprevalence of anti-adeno-associated viral vector neutralizing antibodies among racial minorities in the United States. Hum Gene Ther, 2022; 33(7–8):442–450; doi: 10.1089/hum.2021.243
53.
WangD, ZhongL, LiM, et al.Adeno-associated virus neutralizing antibodies in large animals and their impact on brain intraparenchymal gene transfer. Mol Ther Methods Clin Dev, 2018; 11:65–72; doi: 10.1016/j.omtm.2018.09.003
54.
Davis-GardnerME, WeberJA, XieJ, et al.A strategy for high antibody expression with low anti-drug antibodies using AAV9 vectors. Front Immunol, 2023; 14:1105617; doi: 10.3389/fimmu.2023.1105617
55.
GaoG, AlviraMR, SomanathanS, et al.Adeno-associated viruses undergo substantial evolution in primates during natural infections. Proc Natl Acad Sci U S A, 2003; 100(10):6081–6086; doi: 10.1073/pnas.0937739100
56.
MendellJR, ConnollyAM, LehmanKJ, et al.Testing preexisting antibodies prior to AAV gene transfer therapy: Rationale, lessons and future considerations. Mol Ther Methods Clin Dev, 2022; 25:74–83; doi: 10.1016/j.omtm.2022.02.011
57.
StrobelB, ZuckschwerdtK, ZimmermannG, et al.Standardized, scalable, and timely flexible adeno-associated virus vector production using frozen high-density HEK-293 cell stocks and CELLdiscs. Hum Gene Ther Methods, 2019; 30(1):23–33; doi: 10.1089/hgtb.2018.228
58.
StrobelB, DuchsMJ, BlazevicD, et al.A small-molecule-responsive riboswitch enables conditional induction of viral vector-mediated gene expression in mice. ACS Synth Biol, 2020; 9(6):1292–1305; doi: 10.1021/acssynbio.9b00410
59.
HulsenT, de VliegJ, AlkemaW. BioVenn—A web application for the comparison and visualization of biological lists using area-proportional Venn diagrams. BMC Genomics, 2008; 9:488; doi: 10.1186/1471-2164-9-488
60.
AmatoR, GardinJF, ToozeJA, et al.Organ weights in relation to age and sex in cynomolgus monkeys (Macaca fascicularis). Toxicol Pathol, 2022; 50(5):574–590; doi: 10.1177/01926233221088283
61.
FitzpatrickZ, LeborgneC, BarbonE, et al.Influence of pre-existing anti-capsid neutralizing and binding antibodies on AAV vector transduction. Mol Ther Methods Clin Dev, 2018; 9:119–129; doi: 10.1016/j.omtm.2018.02.003
62.
SchulzM, LevyDI, PetropoulosCJ, et al.Binding and neutralizing anti-AAV antibodies: Detection and implications for rAAV-mediated gene therapy. Mol Ther, 2023; 31(3):616–630; doi: 10.1016/j.ymthe.2023.01.010
63.
LiuQ, HuangW, ZhangH, et al.Neutralizing antibodies against AAV2, AAV5 and AAV8 in healthy and HIV-1-infected subjects in China: Implications for gene therapy using AAV vectors. Gene Ther, 2014; 21(8):732–738; doi: 10.1038/gt.2014.47
64.
Bantel-SchaalU, Zur HausenH. Characterization of the DNA of a defective human parvovirus isolated from a genital site. Virology, 1984; 134(1):52–63; doi: 10.1016/0042-6822(84)90271-x
65.
Bantel-SchaalU, DeliusH, SchmidtR, et al.Human adeno-associated virus type 5 is only distantly related to other known primate helper-dependent parvoviruses. J Virol, 1999; 73(2):939–947; doi: 10.1128/JVI.73.2.939-947.1999
66.
ChioriniJA, KimF, YangL, et al.Cloning and characterization of adeno-associated virus type 5. J Virol, 1999; 73(2):1309–1319; doi: 10.1128/JVI.73.2.1309-1319.1999
67.
ChioriniJA, AfioneS, KotinRM. Adeno-associated virus (AAV) type 5 Rep protein cleaves a unique terminal resolution site compared with other AAV serotypes. J Virol, 1999; 73(5):4293–4298; doi: 10.1128/JVI.73.5.4293-4298.1999
68.
ZabnerJ, SeilerM, WaltersR, et al.Adeno-associated virus type 5 (AAV5) but not AAV2 binds to the apical surfaces of airway epithelia and facilitates gene transfer. J Virol, 2000; 74(8):3852–3858; doi: 10.1128/jvi.74.8.3852-3858.2000
69.
AliskyJM, HughesSM, SauterSL, et al.Transduction of murine cerebellar neurons with recombinant FIV and AAV5 vectors. Neuroreport, 2000; 11(12):2669–2673; doi: 10.1097/00001756-200008210-00013
70.
BurgerC, GorbatyukOS, VelardoMJ, et al.Recombinant AAV viral vectors pseudotyped with viral capsids from serotypes 1, 2, and 5 display differential efficiency and cell tropism after delivery to different regions of the central nervous system. Mol Ther, 2004; 10(2):302–317; doi: 10.1016/j.ymthe.2004.05.024
71.
YangGS, SchmidtM, YanZ, et al.Virus-mediated transduction of murine retina with adeno-associated virus: Effects of viral capsid and genome size. J Virol, 2002; 76(15):7651–7660; doi: 10.1128/jvi.76.15.7651-7660.2002
SummerfordC, SamulskiRJ. Membrane-associated heparan sulfate proteoglycan is a receptor for adeno-associated virus type 2 virions. J Virol, 1998; 72(2):1438–1445; doi: 10.1128/JVI.72.2.1438-1445.1998
74.
TakedaS, TakahashiM, MizukamiH, et al.Successful gene transfer using adeno-associated virus vectors into the kidney: Comparison among adeno-associated virus serotype 1-5 vectors in vitro and in vivo. Nephron Exp Nephrol, 2004; 96(4):e119–e126; doi: 10.1159/000077378
75.
QiYF, LiQH, ShenoyV, et al.Comparison of the transduction efficiency of tyrosine-mutant adeno-associated virus serotype vectors in kidney. Clin Exp Pharmacol Physiol, 2013; 40(1):53–55; doi: 10.1111/1440-1681.12037
76.
YinL, GreenbergK, HunterJJ, et al.Intravitreal injection of AAV2 transduces macaque inner retina. Invest Ophthalmol Vis Sci, 2011; 52(5):2775–2783; doi: 10.1167/iovs.10-6250
77.
WassmerSJ, CarvalhoLS, GyorgyB, et al.Exosome-associated AAV2 vector mediates robust gene delivery into the murine retina upon intravitreal injection. Sci Rep, 2017; 7:45329; doi: 10.1038/srep45329
78.
LoganGJ, DaneAP, HallwirthCV, et al.Identification of liver-specific enhancer-promoter activity in the 3′ untranslated region of the wild-type AAV2 genome. Nat Genet, 2017; 49(8):1267–1273; doi: 10.1038/ng.3893
79.
NiemeyerGP, HerzogRW, MountJ, et al.Long-term correction of inhibitor-prone hemophilia B dogs treated with liver-directed AAV2-mediated factor IX gene therapy. Blood, 2009; 113(4):797–806; doi: 10.1182/blood-2008-10-181479
80.
AbadieJ, BlouinV, GuigandL, et al.Recombinant adeno-associated virus type 2 mediates highly efficient gene transfer in regenerating rat skeletal muscle. Gene Ther, 2002; 9(15):1037–1043; doi: 10.1038/sj.gt.3301773
81.
LouboutinJP, WangL, WilsonJM. Gene transfer into skeletal muscle using novel AAV serotypes. J Gene Med, 2005; 7(4):442–451; doi: 10.1002/jgm.686
82.
GriffeyM, BibleE, VoglerC, et al.Adeno-associated virus 2-mediated gene therapy decreases autofluorescent storage material and increases brain mass in a murine model of infantile neuronal ceroid lipofuscinosis. Neurobiol Dis, 2004; 16(2):360–369; doi: 10.1016/j.nbd.2004.03.005
83.
KlamrothR, HayesG, AndreevaT, et al.Global seroprevalence of pre-existing immunity against AAV5 and other AAV serotypes in people with hemophilia A. Hum Gene Ther, 2022; 33(7–8):432–441; doi: 10.1089/hum.2021.287
84.
GaoGP, AlviraMR, WangL, et al.Novel adeno-associated viruses from rhesus monkeys as vectors for human gene therapy. Proc Natl Acad Sci U S A, 2002; 99(18):11854–11859; doi: 10.1073/pnas.182412299
85.
PanedaA, VanrellL, MauleonI, et al.Effect of adeno-associated virus serotype and genomic structure on liver transduction and biodistribution in mice of both genders. Hum Gene Ther, 2009; 20(8):908–917; doi: 10.1089/hum.2009.031
86.
NamHJ, LaneMD, PadronE, et al.Structure of adeno-associated virus serotype 8, a gene therapy vector. J Virol, 2007; 81(22):12260–12271; doi: 10.1128/JVI.01304-07
87.
Cabanes-CreusM, NavarroRG, ZhuE, et al.Novel human liver-tropic AAV variants define transferable domains that markedly enhance the human tropism of AAV7 and AAV8. Mol Ther Methods Clin Dev, 2022; 24:88–101; doi: 10.1016/j.omtm.2021.11.011
88.
BroekmanML, ComerLA, HymanBT, et al.Adeno-associated virus vectors serotyped with AAV8 capsid are more efficient than AAV-1 or -2 serotypes for widespread gene delivery to the neonatal mouse brain. Neuroscience, 2006; 138(2):501–510; doi: 10.1016/j.neuroscience.2005.11.057
89.
WatakabeA, OhtsukaM, KinoshitaM, et al.Comparative analyses of adeno-associated viral vector serotypes 1, 2, 5, 8 and 9 in marmoset, mouse and macaque cerebral cortex. Neurosci Res, 2015; 93:144–157; doi: 10.1016/j.neures.2014.09.002
90.
GardnerMR, MendesDE, MunizCP, et al.High concordance of ELISA and neutralization assays allows for the detection of antibodies to individual AAV serotypes. Mol Ther Methods Clin Dev, 2022; 24:199–206; doi: 10.1016/j.omtm.2022.01.003
91.
KoponenS, KokkiE, TamminenT, et al.AAV2 and AAV9 tropism and transgene expression in the mouse eye and major tissues after intravitreal and subretinal delivery. Front Drug Deliv, 2023; 3:1148795; doi: 10.3389/fddev.2023.1148795
92.
BellCL, VandenbergheLH, BellP, et al.The AAV9 receptor and its modification to improve in vivo lung gene transfer in mice. J Clin Invest, 2011; 121(6):2427–2435; doi: 10.1172/JCI57367
93.
SchievenbuschS, StrackI, SchefflerM, et al.Combined paracrine and endocrine AAV9 mediated expression of hepatocyte growth factor for the treatment of renal fibrosis. Mol Ther, 2010; 18(7):1302–1309; doi: 10.1038/mt.2010.71
94.
ShenX, XuY, BaiZ, et al.Transparenchymal renal pelvis injection of recombinant adeno-associated virus serotype 9 vectors is a practical approach for gene delivery in the kidney. Hum Gene Ther Methods, 2018; 29(6):251–258; doi: 10.1089/hgtb.2018.148
95.
ChenBD, HeCH, ChenXC, et al.Targeting transgene to the heart and liver with AAV9 by different promoters. Clin Exp Pharmacol Physiol, 2015; 42(10):1108–1117; doi: 10.1111/1440-1681.12453
96.
InagakiK, FuessS, StormTA, et al.Robust systemic transduction with AAV9 vectors in mice: Efficient global cardiac gene transfer superior to that of AAV8. Mol Ther, 2006; 14(1):45–53; doi: 10.1016/j.ymthe.2006.03.014
97.
PulicherlaN, ShenS, YadavS, et al.Engineering liver-detargeted AAV9 vectors for cardiac and musculoskeletal gene transfer. Mol Ther, 2011; 19(6):1070–1078; doi: 10.1038/mt.2011.22
98.
CearleyCN, WolfeJH. Transduction characteristics of adeno-associated virus vectors expressing cap serotypes 7, 8, 9, and Rh10 in the mouse brain. Mol Ther, 2006; 13(3):528–537; doi: 10.1016/j.ymthe.2005.11.015
99.
FoustKD, NurreE, MontgomeryCL, et al.Intravascular AAV9 preferentially targets neonatal neurons and adult astrocytes. Nat Biotechnol, 2009; 27(1):59–65; doi: 10.1038/nbt.1515
100.
DuqueS, JoussemetB, RiviereC, et al.Intravenous administration of self-complementary AAV9 enables transgene delivery to adult motor neurons. Mol Ther, 2009; 17(7):1187–1196; doi: 10.1038/mt.2009.71
101.
BevanAK, DuqueS, FoustKD, et al.Systemic gene delivery in large species for targeting spinal cord, brain, and peripheral tissues for pediatric disorders. Mol Ther, 2011; 19(11):1971–1980; doi: 10.1038/mt.2011.157
102.
CastleMJ, PerlsonE, HolzbaurEL, et al.Long-distance axonal transport of AAV9 is driven by dynein and kinesin-2 and is trafficked in a highly motile Rab7-positive compartment. Mol Ther, 2014; 22(3):554–566; doi: 10.1038/mt.2013.237
103.
StolteB, Schreiber-KatzO, GuntherR, et al.Prevalence of anti-adeno-associated virus serotype 9 antibodies in adult patients with spinal muscular atrophy. Hum Gene Ther, 2022; 33(17–18):968–976; doi: 10.1089/hum.2022.054
104.
GaoG, VandenbergheLH, AlviraMR, et al.Clades of adeno-associated viruses are widely disseminated in human tissues. J Virol, 2004; 78(12):6381–6388; doi: 10.1128/JVI.78.12.6381-6388.2004
105.
GaoG, VandenbergheLH, WilsonJM. New recombinant serotypes of AAV vectors. Curr Gene Ther, 2005; 5(3):285–297; doi: 10.2174/1566523054065057
106.
AkacheB, GrimmD, PandeyK, et al.The 37/67-kilodalton laminin receptor is a receptor for adeno-associated virus serotypes 8, 2, 3, and 9. J Virol, 2006; 80(19):9831–9836; doi: 10.1128/JVI.00878-06
TseLV, KlincKA, MadiganVJ, et al.Structure-guided evolution of antigenically distinct adeno-associated virus variants for immune evasion. Proc Natl Acad Sci U S A, 2017; 114(24):E4812–E4821; doi: 10.1073/pnas.1704766114
109.
LeborgneC, BarbonE, AlexanderJM, et al.IgG-cleaving endopeptidase enables in vivo gene therapy in the presence of anti-AAV neutralizing antibodies. Nat Med, 2020; 26(7):1096–1101; doi: 10.1038/s41591-020-0911-7
Supplementary Material
Please find the following supplemental material available below.
For Open Access articles published under a Creative Commons License, all supplemental material carries the same license as the article it is associated with.
For non-Open Access articles published, all supplemental material carries a non-exclusive license, and permission requests for re-use of supplemental material or any part of supplemental material shall be sent directly to the copyright owner as specified in the copyright notice associated with the article.
