Evaluating the state of the science for adeno-associated virus integration: An integrated perspective.
Mol Ther
; 30(8): 2646-2663, 2022 08 03.
Article
em En
| MEDLINE
| ID: mdl-35690906
ABSTRACT
On August 18, 2021, the American Society of Gene and Cell Therapy (ASGCT) hosted a virtual roundtable on adeno-associated virus (AAV) integration, featuring leading experts in preclinical and clinical AAV gene therapy, to further contextualize and understand this phenomenon. Recombinant AAV (rAAV) vectors are used to develop therapies for many conditions given their ability to transduce multiple cell types, resulting in long-term expression of transgenes. Although most rAAV DNA typically remains episomal, some rAAV DNA becomes integrated into genomic DNA at a low frequency, and rAAV insertional mutagenesis has been shown to lead to tumorigenesis in neonatal mice. Currently, the risk of rAAV-mediated oncogenesis in humans is theoretical because no confirmed genotoxic events have been reported to date. However, because insertional mutagenesis has been reported in a small number of murine studies, there is a need to characterize this genotoxicity to inform research, regulatory needs, and patient care. The purpose of this white paper is to review the evidence of rAAV-related host genome integration in animal models and possible risks of insertional mutagenesis in patients. In addition, technical considerations, regulatory guidance, and bioethics are discussed.
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Texto completo:
1
Bases de dados:
MEDLINE
Assunto principal:
Dependovirus
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Vetores Genéticos
Tipo de estudo:
Guideline
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Risk_factors_studies
Limite:
Animals
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Humans
Idioma:
En
Revista:
Mol Ther
Assunto da revista:
BIOLOGIA MOLECULAR
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TERAPEUTICA
Ano de publicação:
2022
Tipo de documento:
Article