title: A largely random AAV integration profile after LPLD gene therapy.
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.
authors.affiliation: National Center for Tumor Diseases and German Cancer Research Center, Heidelberg, Germany.
authors.forename: Christine
authors.initials: C
authors.lastname: Kaeppel
authors.forename: Stuart G
authors.initials: SG
authors.lastname: Beattie
authors.forename: Raffaele
authors.initials: R
authors.lastname: Fronza
authors.forename: Richard
authors.initials: R
authors.lastname: van Logtenstein
authors.forename: Florence
authors.initials: F
authors.lastname: Salmon
authors.forename: Sabine
authors.initials: S
authors.lastname: Schmidt
authors.forename: Stephan
authors.initials: S
authors.lastname: Wolf
authors.forename: Ali
authors.initials: A
authors.lastname: Nowrouzi
authors.forename: Hanno
authors.initials: H
authors.lastname: Glimm
authors.forename: Christof
authors.initials: C
authors.lastname: von Kalle
authors.forename: Harald
authors.initials: H
authors.lastname: Petry
authors.forename: Daniel
authors.initials: D
authors.lastname: Gaudet
authors.forename: Manfred
authors.initials: M
authors.lastname: Schmidt
mesh_terms: D000818:Animals; D001665:Binding Sites / Q000235:genetics; D000229:Dependovirus / Q000235:genetics* / Q000502:physiology; D015316:Genetic Therapy / Q000009:adverse effects; D005822:Genetic Vectors / Q000008:administration & dosage / Q000009:adverse effects / Q000235:genetics / Q000502:physiology; D006801:Humans; D008072:Hyperlipoproteinemia Type I / Q000235:genetics*; D007273:Injections, Intramuscular; D008071:Lipoprotein Lipase / Q000008:administration & dosage / Q000172:deficiency / Q000235:genetics; D051379:Mice; D008810:Mice, Inbred C57BL; D008954:Models, Biological; D016254:Mutagenesis, Insertional / Q000235:genetics / Q000502:physiology; D059467:Transcriptome; D016662:Virus Integration / Q000235:genetics / Q000502:physiology*
chemical_list: D008071:Lipoprotein Lipase