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Development of iRGD-Modified Peptide Carriers for Suicide Gene Therapy of Uterine Leiomyoma
Anna Egorova1, Sofia Shtykalova1, Alexander Selutin2
1Department of Genomic Medicine, D.O. Ott Research Institute of Obstetrics, Gynecology and Reproductology, Mendeleevskaya line 3, 199034 Saint-Petersburg, Russia.
Abstract:
Uterine leiomyoma (UL) is one of the most common benign tumors in women that often leads to many reproductive complications. Suicide genetherapy was suggested as a promising approach for UL treatment. In the present study, we describe iRGD ligand-conjugated cysteine-rich peptide carrier RGD1-R6 for targeted DNA delivery to αvβ3 integrin-expressing primary UL cells. The physico-chemical properties, cytotoxicity, transfection efficiency and specificity of DNA/RGD1-R6 polyplexes were investigated. TheHSV-1thymidine kinase encoding plasmid delivery to PANC-1pancreatic carcinoma cells and primary UL cells resulted in significant suicide gene therapy effects. Subsequent ganciclovir treatment decreased cells proliferative activity, induced of apoptosis and promoted cells death.The obtained results allow us to concludethatthe developed RGD1-R6 carrier can be considered a promising candidate for suicide gene therapy of uterine leiomyoma.
Insights
Researchers developed a novel peptide carrier (RGD1-R6) for targeted gene therapy in uterine leiomyoma (UL). This approach shows promise for effectively treating UL by delivering therapeutic genes to cancer cells, leading to reduced proliferation and increased cell death.
Area of Science:
- Biomedical Engineering
- Oncology
- Gene Therapy
Background:
- Uterine leiomyoma (UL) is a common benign tumor in women, causing significant reproductive issues.
- Suicide gene therapy presents a promising therapeutic strategy for UL treatment.
- Targeted delivery systems are crucial for enhancing the efficacy of gene therapy.
Purpose of the Study:
- To develop and evaluate an iRGD ligand-conjugated peptide carrier (RGD1-R6) for targeted DNA delivery to UL cells.
- To investigate the physico-chemical properties, cytotoxicity, transfection efficiency, and specificity of the DNA/RGD1-R6 polyplexes.
- To assess the therapeutic potential of the RGD1-R6 carrier in a suicide gene therapy approach for UL.
Main Methods:
- Conjugation of iRGD ligand to a cysteine-rich peptide carrier (RGD1-R6).
- Formation and characterization of DNA/RGD1-R6 polyplexes.
- In vitro evaluation of cytotoxicity, transfection efficiency, and specificity in primary UL cells and PANC-1 cells.
- Assessment of suicide gene therapy efficacy using HSV-1 thymidine kinase gene and ganciclovir treatment.
Main Results:
- The RGD1-R6 carrier demonstrated favorable physico-chemical properties and low cytotoxicity.
- Effective and specific DNA delivery to αvβ3 integrin-expressing primary UL cells was achieved.
- The HSV-1 thymidine kinase gene delivery via RGD1-R6 polyplexes resulted in significant suicide gene therapy effects.
- Ganciclovir treatment post-transfection led to decreased cell proliferation, induced apoptosis, and promoted cell death in treated cells.
Conclusions:
- The developed RGD1-R6 carrier is a promising candidate for targeted DNA delivery in uterine leiomyoma.
- This targeted gene therapy approach shows significant potential for the effective treatment of uterine leiomyoma.
- Further studies are warranted to explore the in vivo efficacy and clinical translation of this therapeutic strategy.
