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Large-scale molecular epidemiological analysis of AAV in a cancer patient population.

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机构： [1]State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, China [2]Horae Gene Therapy Center, University of Massachusetts, Medical School, Worcester, MA, USA [3]Microbiology and Physiological Systems, University of Massachusetts, Medical School, Worcester, MA, USA [4]Fornax Biotech, Worcester, MA, USA [5]Biobank, West China Hospital, Sichuan University, Chengdu, China [6]Department of Thoracic Oncology and State Key Laboratory of Biotherapy, Cancer Center, West China Hospital, Sichuan University, Chengdu, China [7]Pathology Department and State Key Laboratory of Biotherapy, West China Hospital, West China Medical School, Sichuan University, Chengdu, China [8]Department of Urology, Institute of Urology, West China Hospital, Sichuan University, Chengdu, China [9]Department of Liver Surgery, West China Hospital, Sichuan University, Chengdu, China [10]Department of Gastrointestinal Surgery and Laboratory of Gastric Cancer, West China Hospital, Sichuan University, Chengdu, China [11]Pediatrics, University of Massachusetts, Medical School, Worcester, MA, USA

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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.

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出版当年[2021]版：

大类 | 1 区

医学

小类 | 1 区生化与分子生物学 1 区肿瘤学 1 区遗传学 2 区细胞生物学

最新[2023]版：

大类 | 1 区

医学

小类 | 1 区生化与分子生物学 1 区遗传学 2 区细胞生物学 2 区肿瘤学

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第一作者机构： [1]State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, China

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通讯机构： [2]Horae Gene Therapy Center, University of Massachusetts, Medical School, Worcester, MA, USA [3]Microbiology and Physiological Systems, University of Massachusetts, Medical School, Worcester, MA, USA [11]Pediatrics, University of Massachusetts, Medical School, Worcester, MA, USA

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