Intraperitoneal administration of adeno-associated virus encoding microRNA-29b for the treatment of peritoneal metastasis.

Autor: Kaneko Y; Department of Surgery, Jichi Medical University, Shimotsuke, Japan., Ohzawa H; Department of Clinical Oncology, Jichi Medical University, Shimotsuke, Japan., Kimura Y; Department of Surgery, Jichi Medical University, Shimotsuke, Japan., Takahashi R; Department of Surgery, Jichi Medical University, Shimotsuke, Japan., Matsumiya M; Department of Surgery, Jichi Medical University, Shimotsuke, Japan., Tamura K; Department of Obstetrics and Gynecology, Jichi Medical University, Shimotsuke, Japan., Futoh Y; Department of Surgery, Jichi Medical University, Shimotsuke, Japan., Miyato H; Department of Surgery, Jichi Medical University, Shimotsuke, Japan., Saito S; Department of Surgery, Jichi Medical University, Shimotsuke, Japan., Yamaguchi H; Department of Clinical Oncology, Jichi Medical University, Shimotsuke, Japan., Hosoya Y; Department of Surgery, Jichi Medical University, Shimotsuke, Japan., Watano R; Division of Genetic Therapeutics, Center for Molecular Medicine, Jichi Medical University, Shimotsuke, Japan., Mizukami H; Division of Genetic Therapeutics, Center for Molecular Medicine, Jichi Medical University, Shimotsuke, Japan., Sata N; Department of Surgery, Jichi Medical University, Shimotsuke, Japan., Kitayama J; Department of Surgery, Jichi Medical University, Shimotsuke, Japan. kitayama@jichi.ac.jp.; Center for Clinical Research, Jichi Medical University Hospital, Shimotsuke, Japan. kitayama@jichi.ac.jp.
Jazyk: angličtina
Zdroj: Cancer gene therapy [Cancer Gene Ther] 2024 Dec; Vol. 31 (12), pp. 1818-1830. Date of Electronic Publication: 2024 Oct 10.
DOI: 10.1038/s41417-024-00837-w
Abstrakt: This study explores a novel therapeutic approach for peritoneal metastasis (PM) using AAV-mediated delivery of tumor suppressor microRNA-29b (miR-29b) to peritoneal mesothelial cells (PMC). AAV serotypes 2 and DJ demonstrate high transduction efficiency for human and murine PMC, respectively. In vitro analysis indicates that AAV vectors encoding miR-29b precursor successfully elevate miR-29b expression in PMC and their secreted small extracellular vesicle (sEV), thereby inhibiting mesothelial mesenchymal transition and reducing subsequent attachment of tumor cells. A single intraperitoneal (IP) administration of AAV-DJ-miR-29b demonstrates robust and sustained transgene expression, suppressing peritoneal fibrosis and inhibiting the development of PM from gastric and pancreatic cancers. Additionally, AAV-DJ-miR-29b enhances the efficacy of IP chemotherapy using paclitaxel, restraining the growth of established PM. While conventional gene therapy for cancer encounters challenges targeting tumor cells directly but delivering miRNA to the tumor stroma offers a straightforward and efficient means of altering the microenvironment, leading to substantial inhibition of tumor growth. AAV-mediated miR-29b delivery to peritoneum via IP route presents a simple, minimally invasive, and promising therapeutic strategy for refractory PM.
Competing Interests: Competing interests: The authors declare no competing interests. Ethical statement and approval: All methods in the research were performed in accordance with the relevant guidelines and regulations. Approval of the research protocol by an Institutional Reviewer Board: The protocol was approved by the Institutional Review Boards of Jichi Medical University (approval number: RIN-A-21-048). Written informed consent was obtained from all patients who provided omental samples for this study. Animal study: The protocol of animal study was approved by Institution Review Board of the Animal Care Committee of Jichi Medical University (approval no. 21045-01, 23007-01).
(© 2024. The Author(s), under exclusive licence to Springer Nature America, Inc.)
Databáze: MEDLINE
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