Abstract
Recombinant adeno-associated viruses (rAAVs) are well-established vectors for delivering therapeutic genes. However, previous reports have suggested that wild-type AAV is linked to hepatocellular carcinoma, raising concern with the safety of rAAVs. In addition, a recent long-term follow-up study in canines, which received rAAVs for factor VIII gene therapy, demonstrated vector integration into the genome of liver cells, reviving the uncertainty between AAV and cancer. To further explore this relationship, we performed large-scale molecular epidemiology of AAV in resected tumor samples and non-lesion tissues collected from 413 patients, reflecting nine carcinoma types: breast carcinoma, rectal cancer, pancreas carcinoma, brain tumor, hepatoid adenocarcinoma, hepatocellular carcinoma, gastric carcinoma, lung squamous, and adenocarcinoma. We found that over 80% of patients were AAV-positive among all nine types of carcinoma examined. Importantly, the AAV sequences detected in patient-matched tumor and adjacent non-lesion tissues showed no significant difference in incidence, abundance, and variation. In addition, no specific AAV sequences predominated in tumor samples. Our data shows that AAV genomes are equally abundant in tumors and adjacent normal tissues, but lack clonality. The finding critically adds to the epidemiological profile of AAV in humans, and provides insights that may assist rAAV-based clinical studies and gene therapy strategies.