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Updated: Nov 30, 2025
Subpial Adeno-associated Virus 9 AAV9 Vector Delivery in Adult Mice
Published on: July 13, 2017
Recombinant Adeno-associated Virus 9-mediated Expression of Kallistatin Suppresses Lung Tumor Growth in Mice
Weihong Qu1, Jianguo Zhao1, Yaqing Wu1
1Department of School of Pharmacy & Life Science, Jiujiang University, Jiujiang, Jiangxi 332000, China.
Background:
Lung cancer remains the most common cause of cancer-related deaths in China and worldwide. Traditional surgery and chemotherapy do not offer an effective cure, although gene therapy may be a promising future alternative. Kallistatin (Kal) is an endogenous inhibitor of angiogenesis and tumorigenesis. Recombinant adeno-associated virus (rAAV) is considered the most promising vector for gene therapy of many diseases due to persistent and long-term transgenic expression.
Objective:
The aim of this study was to investigate whether rAAV9-Kal inhibited NCI-H446 subcutaneous xenograft tumor growth in mice.
Methods:
The subcutaneous xenograft mode was induced by subcutaneous injection of 2×107 H446 cells into the dorsal skin of BALB/c nude mice. The mice were administered with ssrAAV9-Kal (single- stranded rAAV9) or dsrAAV9-Kal (double-stranded rAAV9) by intraperitoneal injection (I.P.). Tumor microvessel density (MVD) was examined by anti-CD34 staining to evaluate tumor angiogenesis.
Results:
Compared with the PBS (blank control) group, tumor growth in the high-dose ssrAAV9-Kal group was inhibited by 40% by day 49, and the MVD of tumor tissues was significantly decreased.
Conclusion:
The results indicate that this therapeutic strategy is a promising approach for clinical cancer therapy and implicate rAAV9-Kal as a candidate for gene therapy of lung cancer.
Insights
Recombinant adeno-associated virus carrying Kallistatin (rAAV9-Kal) gene therapy significantly inhibited lung cancer growth in mice. This approach reduced tumor size and microvessel density, showing promise for clinical cancer treatment.
Area of Science:
- Oncology
- Gene Therapy
- Molecular Biology
Background:
- Lung cancer is a leading cause of cancer deaths globally.
- Current treatments like surgery and chemotherapy have limitations.
- Gene therapy presents a promising alternative, with recombinant adeno-associated virus (rAAV) as a potential vector.
Purpose of the Study:
- To evaluate the efficacy of rAAV9-Kal in inhibiting NCI-H446 lung cancer xenograft growth in mice.
- To assess the impact of rAAV9-Kal on tumor angiogenesis.
Main Methods:
- Establishment of subcutaneous xenografts using NCI-H446 cells in BALB/c nude mice.
- Administration of single-stranded (ssrAAV9-Kal) or double-stranded (dsrAAV9-Kal) rAAV9-Kal via intraperitoneal injection.
- Assessment of tumor microvessel density (MVD) using anti-CD34 staining.
Main Results:
- High-dose ssrAAV9-Kal significantly inhibited tumor growth by 40% compared to the control group.
- A significant decrease in tumor microvessel density was observed in the treated group.
- rAAV9-Kal demonstrated anti-angiogenic and anti-tumorigenic effects.
Conclusions:
- rAAV9-Kal gene therapy is a promising strategy for lung cancer treatment.
- This approach warrants further investigation for clinical application in lung cancer.
- Kallistatin delivered via rAAV9 shows potential as a therapeutic agent for lung cancer.
