Restricted accessEditorialFirst published online 2023-11
Integration of Gene Therapy Vectors: A Risk Factor for Tumorigenesis or Another Commensal Property of Adeno-Associated Viruses That Benefits Long-Term Transgene Expression?
ConroyG. How gene therapy is emerging from its ‘dark age’. Nature, 2022; 612(7940):S24–S26; doi: 10.1038/d41586-022-04210-5
2.
ShenW, LiuS, OuL. rAAV immunogenicity, toxicity, and durability in 255 clinical trials: A meta-analysis. Front Immunol, 2022; 13:1001263; doi: 10.3389/fimmu.2022.1001263
3.
MullardA. FDA approves first haemophilia B gene therapy. Nat Rev Drug Discov, 2023; 22(1):7; doi: 10.1038/d41573-022-00199-8
4.
HoySM. Delandistrogene moxeparvovec: First approval. Drugs, 2023; In Press; doi: 10.1007/s40265-023-01929-x
5.
KotinRM, SiniscalcoM, SamulskiRJ, et al.Site-specific integration by adeno-associated virus. Proc Natl Acad Sci U S A, 1990; 87(6):2211–2215; doi: 10.1073/pnas.87.6.2211
6.
DonsanteA, MillerDG, LiY, et al.AAV vector integration sites in mouse hepatocellular carcinoma. Science, 2007; 317(5837):477; doi: 10.1126/science.1142658
7.
BernsKI, ByrneBJ, FlotteTR, et al.Adeno-associated virus type 2 and hepatocellular carcinoma?. Hum Gene Ther, 2015; 26(12):779–781; doi: 10.1089/hum.2015.29014.kib
8.
SabatinoDE, BushmanFD, ChandlerRJ, et al.Evaluating the state of the science for adeno-associated virus integration: An integrated perspective. Mol Ther, 2022; 30(8):2646–2663; doi: 10.1016/j.ymthe.2022.06.004
9.
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
10.
NguyenGN, EverettJK, KafleS, 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(1):47–55; doi: 10.1038/s41587-020-0741-7
11.
DalwadiDA, CalabriaA, TiyaboonchaiA, et al.AAV integration in human hepatocytes. Mol Ther, 2021; 29(10):2898–2909; doi: 10.1016/j.ymthe.2021.08.031
12.
SchmidtM, FosterGR, CoppensM, et al.Molecular evaluation and vector integration analysis of HCC complicating AAV gene therapy for hemophilia B. Blood Adv, 2023; 7(17):4966–4969; doi: 10.1182/bloodadvances.2023009876
13.
BretonC, ClarkPM, WangL, et al.ITR-Seq, a next-generation sequencing assay, identifies genome-wide DNA editing sites in vivo following adeno-associated viral vector-mediated genome editing. BMC Genomics, 2020; 21(1):239; doi: 10.1186/s12864-020-6655-4
14.
TaiPWL, XieJ, FongK, et al.Adeno-associated virus genome population sequencing achieves full vector genome resolution and reveals human-vector chimeras. Mol Ther Methods Clin Dev, 2018; 9:130–141; doi: 10.1016/j.omtm.2018.02.002
