Related Experiment Video
Updated: Jun 7, 2026
Systemic Delivery of MicroRNA Using Recombinant Adeno-associated Virus Serotype 9 to Treat Neuromuscular Diseases in Rodents
Published on: August 10, 2018
Intraperitoneal administration of adeno-associated virus encoding microRNA-29b for the treatment of peritoneal
Yuki Kaneko1, Hideyuki Ohzawa2, Yuki Kimura1
1Department of Surgery, Jichi Medical University, Shimotsuke, Japan.
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.
Insights
This study shows that delivering microRNA-29b (miR-29b) using adeno-associated virus (AAV) to peritoneal mesothelial cells can effectively treat peritoneal metastasis. This novel gene therapy approach inhibits cancer spread and enhances chemotherapy for difficult-to-treat peritoneal cancers.
Area of Science:
- Oncology
- Gene Therapy
- Nanomedicine
Background:
- Peritoneal metastasis (PM) is a significant challenge in advanced cancers, particularly gastric and pancreatic.
- Current treatments for PM have limited efficacy, necessitating novel therapeutic strategies.
- Altering the peritoneal microenvironment holds promise for controlling tumor cell dissemination.
Purpose of the Study:
- To investigate the efficacy of adeno-associated virus (AAV)-mediated delivery of tumor suppressor microRNA-29b (miR-29b) to peritoneal mesothelial cells (PMCs) for treating PM.
- To evaluate the potential of AAV-DJ-miR-29b as a therapeutic agent for inhibiting peritoneal metastasis and enhancing chemotherapy.
Main Methods:
- Adeno-associated virus (AAV) serotypes 2 and DJ were used for efficient transduction of human and murine PMCs.
- In vitro studies assessed miR-29b expression in PMCs and their secreted small extracellular vesicles (sEVs) after AAV vector delivery.
- In vivo studies involved single intraperitoneal (IP) administration of AAV-DJ-miR-29b in mouse models of gastric and pancreatic cancer PM.
Main Results:
- AAV vectors successfully delivered miR-29b precursor to PMCs, increasing miR-29b levels and inhibiting mesothelial-mesenchymal transition.
- AAV-DJ-miR-29b administration suppressed peritoneal fibrosis and inhibited the development of PM.
- Combined AAV-DJ-miR-29b therapy with IP paclitaxel significantly restrained established PM growth.
Conclusions:
- AAV-mediated delivery of miR-29b to PMCs via the IP route is a feasible and effective strategy for combating peritoneal metastasis.
- This approach offers a minimally invasive and promising therapeutic option for refractory PM by modifying the tumor microenvironment.
- The combination of gene therapy with chemotherapy demonstrates enhanced efficacy in controlling peritoneal tumor burden.
