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Oncogene
Apr, 2021;40 (17): 3060-3071.

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

Wanru Qin, Guangchao Xu, Phillip W L Tai, Chunmei Wang, Li Luo, Chengjian Li, Xun Hu, Jianxin Xue, You Lu, Qiao Zhou, Qiang Wei, Tianfu Wen, Jiankun Hu, Yuanyuan Xiao, Li Yang, Weimin Li, Terence R Flotte, Yuquan Wei, Guangping Gao
Author Information
  1. Wanru Qin: State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, China. ORCID
  2. Guangchao Xu: State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, China.
  3. Phillip W L Tai: Horae Gene Therapy Center, University of Massachusetts, Medical School, Worcester, MA, USA. ORCID
  4. Chunmei Wang: State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, China.
  5. Li Luo: State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, China.
  6. Chengjian Li: Fornax Biotech, Worcester, MA, USA.
  7. Xun Hu: Biobank, West China Hospital, Sichuan University, Chengdu, China.
  8. Jianxin Xue: Department of Thoracic Oncology and State Key Laboratory of Biotherapy, Cancer Center, West China Hospital, Sichuan University, Chengdu, China.
  9. You Lu: Department of Thoracic Oncology and State Key Laboratory of Biotherapy, Cancer Center, West China Hospital, Sichuan University, Chengdu, China. ORCID
  10. Qiao Zhou: Pathology Department and State Key Laboratory of Biotherapy, West China Hospital, West China Medical School, Sichuan University, Chengdu, China. ORCID
  11. Qiang Wei: Department of Urology, Institute of Urology, West China Hospital, Sichuan University, Chengdu, China.
  12. Tianfu Wen: Department of Liver Surgery, West China Hospital, Sichuan University, Chengdu, China.
  13. Jiankun Hu: Department of Gastrointestinal Surgery and Laboratory of Gastric Cancer, West China Hospital, Sichuan University, Chengdu, China.
  14. Yuanyuan Xiao: State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, China.
  15. Li Yang: State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, China.
  16. Weimin Li: State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, China.
  17. Terence R Flotte: Horae Gene Therapy Center, University of Massachusetts, Medical School, Worcester, MA, USA. Terry.Flotte@umassmed.edu. ORCID
  18. Yuquan Wei: State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, China. yqwei@scu.edu.cn. ORCID
  19. Guangping Gao: Horae Gene Therapy Center, University of Massachusetts, Medical School, Worcester, MA, USA. guangping.gao@umassmed.edu. ORCID
PMID: 33782545 DOI: 10.1038/s41388-021-01725-5

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.

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Grants

  1. R01 HL097088/NHLBI NIH HHS
  2. P01 HL131471/NHLBI NIH HHS
  3. P01 AI100263/NIAID NIH HHS
  4. R01 AI121135/NIAID NIH HHS
  5. R01 NS076991/NINDS NIH HHS
  6. P01HL59407/U.S. Department of Health & Human Services | NIH | National Heart, Lung, and Blood Institute (NHLBI)
  7. UG3 HL147367/NHLBI NIH HHS

MeSH Term

Humans
Dependovirus
Neoplasms
Female
Molecular Epidemiology
Male
Genetic Vectors
Genetic Therapy
Journal Article Research Support, N.I.H., Extramural
Article has an altmetric score of 10

Word Cloud

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