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 (VEGF-A) 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.

用于转染的有效载体的开发是基因工程中的主要挑战之一。先前的研究表明，聚异戊二烯的阳离子衍生物（PTAI）可以作为核酸的载体。在本研究中，研究了两种基于PTAI的配方（PTAI-6-8和10-14）的有效性，并将其与市售试剂进行了比较。应用基因疗法的目的是增强自发性高血压大鼠（SHR）肾髓质中血管内皮生长因子（VEGF-A）的表达，并测试其作为新型抗高血压干预措施的潜力。在研究的第一部分（体外）中，我们确认了基于PTAI的脂质复合物可有效转染XC大鼠肉瘤细胞，并在37°C下稳定7天。在体内实验中 我们将选定的脂质复合物直接注射到有意识的SHR的肾脏中（通过渗透泵）。仅基于PTAI-10-14的制剂，肾脏的髓质无血压变化，且VEGF-A水平显着升高。总之，尽管取得了令人鼓舞的结果，我们仍无法达到足以证明VEGF-A基因治疗在SHR中有用的VEGF-A表达水平。但是，我们的研究结果为基于PTAI的DNA载体的未来发展和以肾脏为目标的基因传递提供了重要的指示。我们无法达到足够高的VEGF-A表达水平，无法验证VEGF-A基因治疗在SHR中的有效性。但是，我们的研究结果为基于PTAI的DNA载体的未来发展和以肾脏为目标的基因传递提供了重要的指示。我们无法达到足够高的VEGF-A表达水平，无法验证VEGF-A基因治疗在SHR中的有效性。但是，我们的研究结果为基于PTAI的DNA载体的未来发展和以肾脏为目标的基因传递提供了重要的指示。