| RRC ID |
83606
|
| 著者 |
Kaneko Y, Ohzawa H, Kimura Y, Takahashi R, Matsumiya M, Tamura K, Futoh Y, Miyato H, Saito S, Yamaguchi H, Hosoya Y, Watano R, Mizukami H, Sata N, Kitayama J.
|
| タイトル |
Intraperitoneal administration of adeno-associated virus encoding microRNA-29b for the treatment of peritoneal metastasis.
|
| ジャーナル |
Cancer Gene Ther
|
| Abstract |
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.
|
| 巻・号 |
31(12)
|
| ページ |
1818-1830
|
| 公開日 |
2024-12-1
|
| DOI |
10.1038/s41417-024-00837-w
|
| PII |
10.1038/s41417-024-00837-w
|
| PMID |
39390194
|
| MeSH |
Animals
Cell Line, Tumor
Dependovirus* / genetics
Genetic Therapy / methods
Genetic Vectors / administration & dosage
Genetic Vectors / genetics
Humans
Injections, Intraperitoneal
Mice
MicroRNAs* / genetics
Paclitaxel / administration & dosage
Paclitaxel / therapeutic use
Pancreatic Neoplasms / genetics
Pancreatic Neoplasms / pathology
Pancreatic Neoplasms / therapy
Peritoneal Neoplasms* / genetics
Peritoneal Neoplasms* / secondary
Peritoneal Neoplasms* / therapy
|
| IF |
4.534
|
| リソース情報 |
| ヒト・動物細胞 |
NUGC-4(RCB1939)
MKN45(RCB1001) |
