Tissue-specific gene therapy directed to tumor angiogenesis

Area of Science:

• Oncology
• Vascular Biology
• Gene Therapy

Background:

• Gene therapy targeting vascular endothelial cells is crucial for treating vascular diseases and cancers.
• Angiogenesis, the formation of new blood vessels, is a key process in tumor growth and metastasis.

Purpose of the Study:

• To develop and evaluate a tissue-specific gene therapy vector for targeting angiogenic endothelial cells in tumor vasculature.
• To assess the efficacy of the murine preproendothelin-1 (PPE-1) promoter in directing gene expression to angiogenic blood vessels.

Main Methods:

• Adeno-based vectors were engineered with the murine preproendothelin-1 (PPE-1) promoter.
• In vitro studies assessed promoter activity in bovine aortic endothelial cells.
• In vivo studies involved systemic injection of vectors into normal mice and mice bearing Lewis lung carcinoma.

Main Results:

• The PPE-1 promoter demonstrated high gene expression in endothelial cells in vitro.
• Systemic administration showed higher PPE-1 promoter activity in aorta and vascularized organs compared to CMV promoter in normal mice.
• In tumor-bearing mice, the vector specifically targeted and expressed genes in the vasculature of primary tumors and lung metastases, with highest expression in angiogenic endothelial cells.

Conclusions:

• The developed vascular-directed gene therapy approach effectively targets angiogenic endothelial cells in tumor vasculature.
• This strategy holds significant potential for therapeutic applications in both vascular diseases and cancer treatment.