AAV Infection: Protection from Cancer.
There are conflicting reports that integration of the wild-type adeno-associated virus 2 (AAV2) genome is associated with induction of hepatocellular carcinoma (HCC) in a small subset of patients. However, there are several lines of evidence that contradict this assertion: (i) AAV2 has long been known to be a non-pathogenic virus, although ∼90% of the human population is seropositive for AAV2 antibodies; (ii) AAV2 has been shown to possess anticancer activity; (iii) epidemiological evidence suggests that AAV2 infection plays a protective role against cervical carcinoma; and (iv) five different AAV serotype vectors (AAV1, AAV2, AAV5, AAV8, and AAV9) have been or are currently being used in 162 Phase I/II clinical trials and one Phase III clinical trial in humans to date, and no cancer of any type has ever been observed or reported. A brief historical account of the putative role of infection by AAV in the etiology of cancer, or lack thereof, is presented.
1 Division of Cellular and Molecular Therapy, Departments of Pediatrics and Molecular Genetics and Microbiology, Powell Gene Therapy Center; Genetics Institute; University of Florida College of Medicine , Gainesville, Florida.
Arun
A
Srivastava
2 BioMarin Pharmaceutical, Inc. , Novato, California.
Barrie J
BJ
Carter
D000818:Animals; D006528:Carcinoma, Hepatocellular / Q000235:genetics / Q000628:therapy*; D002986:Clinical Trials as Topic; D000229:Dependovirus / Q000145:classification / Q000235:genetics*; D018014:Gene Transfer Techniques; D015316:Genetic Therapy; D005822:Genetic Vectors / Q000627:therapeutic use; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics / Q000628:therapy*; D051379:Mice
DNA integration; liver cancer; recombinant AAV vectors; wild-type AAV2