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Polyprenol‑Based Lipofecting Agents for In Vivo Delivery of Therapeutic DNA to Treat Hypertensive Rats

Gawrys, Olga and Rak, Monika and Baranowska, Iwona and Bobis‑Wozowicz, Sylwia and Szaro, Karolina and Madeja, Zbigniew and Swiezewska, Ewa and Masnyk, Marek and Chmielewski, Marek and Karnas, Elzbieta and Kompanowska‑Jezierska, Elzbieta (2020) Polyprenol‑Based Lipofecting Agents for In Vivo Delivery of Therapeutic DNA to Treat Hypertensive Rats. Biochemical Genetics . pp. 1-21.

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Official URL: https://link.springer.com/article/10.1007/s10528-0...

Abstract

Development of efficient vectors for transfection is one of the major challenges in genetic engineering. Previous research demonstrated that cationic derivatives of polyisoprenoids (PTAI) may serve as carriers of nucleic acids. In the present study,the effectiveness of two PTAI-based formulations (PTAI-6–8 and 10–14) was investigated and compared to the commercial reagents. The purpose of applied gene therapy was to enhance the expression of vascular endothelial growth factor (VEGFA)in the renal medulla of spontaneously hypertensive rats (SHR) and to test its potential as a novel antihypertensive intervention. In the first part of the study (in vitro), we confirmed that PTAI-based lipoplexes efficiently transfect XC rat sarcoma cells and are stable in 37 °C for 7 days. In the in vivo experiments, we administered selected lipoplexes directly to the kidneys of conscious SHR (via osmotic pumps). There were no blood pressure changes and VEGF-A level in renal medulla was significantly higher only for PTAI-10–14-based formulation. In conclusion, despite the promising results, we were not able to achieve VEGF-A expression level high enough to verify VEGF-A gene therapy usefulness in SHR. However, results of our study give important indications for the future development of PTAI-based DNA carriers and kidney-targeted gene delivery.

Item Type:Article
Subjects:Q Science > QH Natural history > QH301 Biology
Divisions:Department of Lipid Biochemistry
ID Code:1949
Deposited By: Ewa Swiezewska
Deposited On:28 Dec 2020 13:06
Last Modified:28 Dec 2020 13:06

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