A largely random AAV integration profile after LPLD gene therapy.

Kaeppel, Christine; Beattie, Stuart G; Fronza, Raffaele; van Logtenstein, Richard; Salmon, Florence; Schmidt, Sabine; Wolf, Stephan; Nowrouzi, Ali et al. · Nat Med · 2013

case_series · Level IV

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Abstract

The clinical application of adeno-associated virus vectors (AAVs) is limited because of concerns about AAV integration-mediated tumorigenicity. We performed integration-site analysis after AAV1-LPL(S447X) intramuscular injection in five lipoprotein lipase-deficient subjects, revealing random nuclear integration and hotspots in mitochondria. We conclude that AAV integration is potentially safe and that vector breakage and integration may occur from each position of the vector genome. Future viral integration-site analyses should include the mitochondrial genome.

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