AAV Joins the Rank of Genotoxic Vectors

Affiliations

¹ Division of Hematology/Oncology, Department of Medicine, Indiana University School of Medicine, Walther Hall, 980 W. Walnut St., Rm. C312J, Indianapolis, IN 46202, USA.
² Department of Medical and Molecular Genetics, Indiana University School of Medicine, Walther Hall 980 W. Walnut Street, R3 C649, Indianapolis, IN 46202-5121, USA. Electronic address: kcornett@iu.edu.

Comment

Utpal P Davé et al. Mol Ther. 2021.

. 2021 Feb 3;29(2):418-419.

doi: 10.1016/j.ymthe.2021.01.007. Epub 2021 Jan 20.

¹ Division of Hematology/Oncology, Department of Medicine, Indiana University School of Medicine, Walther Hall, 980 W. Walnut St., Rm. C312J, Indianapolis, IN 46202, USA.
² Department of Medical and Molecular Genetics, Indiana University School of Medicine, Walther Hall 980 W. Walnut Street, R3 C649, Indianapolis, IN 46202-5121, USA. Electronic address: kcornett@iu.edu.

No abstract available

Comment on

Enhanced Efficacy and Increased Long-Term Toxicity of CNS-Directed, AAV-Based Combination Therapy for Krabbe Disease.
Li Y, Miller CA, Shea LK, Jiang X, Guzman MA, Chandler RJ, Ramakrishnan SM, Smith SN, Venditti CP, Vogler CA, Ory DS, Ley TJ, Sands MS. Li Y, et al. Mol Ther. 2021 Feb 3;29(2):691-701. doi: 10.1016/j.ymthe.2020.12.031. Epub 2021 Jan 1. Mol Ther. 2021. PMID: 33388420 Free PMC article.
Liver Injury Increases the Incidence of HCC following AAV Gene Therapy in Mice.
Dalwadi DA, Torrens L, Abril-Fornaguera J, Pinyol R, Willoughby C, Posey J, Llovet JM, Lanciault C, Russell DW, Grompe M, Naugler WE. Dalwadi DA, et al. Mol Ther. 2021 Feb 3;29(2):680-690. doi: 10.1016/j.ymthe.2020.10.018. Epub 2020 Oct 22. Mol Ther. 2021. PMID: 33554867 Free PMC article.

1. Donsante A., Vogler C., Muzyczka N., Crawford J.M., Barker J., Flotte T., Campbell-Thompson M., Daly T., Sands M.S. Observed incidence of tumorigenesis in long-term rodent studies of rAAV vectors. Gene Ther. 2001;8:1343–1346. - PubMed
1. Chandler R.J., Sands M.S., Venditti C.P. Recombinant Adeno-Associated Viral Integration and Genotoxicity: Insights from Animal Models. Hum. Gene Ther. 2017;28:314–322. - PMC - PubMed
1. Logan G.J., Dane A.P., Hallwirth C.V., Smyth C.M., Wilkie E.E., Amaya A.K., Zhu E., Khandekar N., Ginn S.L., Liao S.H.Y. Identification of liver-specific enhancer-promoter activity in the 3′ untranslated region of the wild-type AAV2 genome. Nat. Genet. 2017;49:1267–1273. - PubMed
1. Nguyen G.N., Everett J.K., Kafle S., Roche A.M., Raymond H.E., Leiby J., Wood C., Assenmacher C.A., Merricks E.P., Long C.T. A long-term study of AAV gene therapy in dogs with hemophilia A identifies clonal expansions of transduced liver cells. Nat. Biotechnol. 2020 doi: 10.1038/s41587-020-0741-7. Published online November 16, 2020. - DOI - PMC - PubMed
1. Li Y., Miller C.A., Shea L.K., Jiang X., Guzman M.A., Chandler R.J., Ramakrishnan S.M., Smith S.N., Venditti C.P., Vogler C.A. Enhanced efficacy and increased long-term toxicity of CNS-directed, AAV-based combination therapy for Krabbe disease. Mol. Ther. 2020;29:691–701. this issue. - PMC - PubMed