AAV Vector Integration Sites in Mouse Hepatocellular Carcinoma

By Anthony Donsante, Daniel G. Miller, Yi Li, C. Vogler, E. Brunt, David W. Russell, M. Sands. Science, 2007

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Immune responses to AAV vectors: overcoming barriers to successful gene therapy. (2013, neutral): “145,146 In more than 15 years of clinicalexperiencewithAAV,therehavebeennoobservationsofclinical eventsrelatedtoAAVintegration.”
Therapeutic in vivo gene transfer for genetic disease using AAV: progress and challenges (2011, background): “)? And third, what is the risk of vector integration, and resulting insertional mutagenesis, with this predominantly non-integrating vector at the doses currently being investigated in live”
State-of-the-art gene-based therapies: the road ahead (2011, background): “In one mouse model, hepatocellular carcinoma resulted from integration near an miRNA locus that is known to be involved in tumorigenesi”
Incorporation of pseudouridine into mRNA enhances translation by diminishing PKR activation (2010, background): “Unlike viral vectors or plasmid DNA, cell-delivered mRNA does not introduce the risk of insertional mutagenesis (2,3).”
Emerging Issues in AAV-Mediated In Vivo Gene Therapy (2017, background): “To date, insertional mutagenesis by AAV gene transfer has been reported in several studies exploiting vector delivery to neonatal mice.(155,157) In particular, two pivotal independent studies showed that a systemic AAV administration to neonatal mice predisposes them to hepatocellular carcinoma (HCC”