Institute of Technology, University of Tartu, Nooruse 1, 50411, Tartu, Estonia.
Department Biochemistry and Biophysics, Stockholm University, S. Arrheniusv 16B, SE-106 91, Stockholm, Sweden.
Sci Rep. 2019 Dec 27;9(1):19926. doi: 10.1038/s41598-019-56455-2.
We have previously developed efficient peptide-based nucleic acid delivery vectors PF14 and NF55, where we have shown that these vectors preferentially transfect lung tissue upon systemic administration with the nucleic acid. In the current work, we have explored the utilization and potential of these vectors for the lung-targeted gene therapy. Accordingly, we assessed the efficacy of these peptides in (i) two different lung disease models - acute lung inflammation and asthma in mice and (ii) using two different nucleic acid cargos - siRNA and pDNA encoding shRNA. Using RNAi against cytokine TNFα, we showed efficient anti-inflammatory effects in both disease models and observed decreased disease symptoms. Our results highlight the potential of our transfection vectors for lung gene therapy.
我们之前开发了高效的基于肽的核酸传递载体 PF14 和 NF55，在体内给药时，这些载体优先转染肺部组织。在目前的工作中，我们探索了这些载体在肺靶向基因治疗中的利用和潜力。因此，我们评估了这些肽在以下方面的功效：（i）两种不同的肺部疾病模型——小鼠的急性肺炎症和哮喘，以及（ii）使用两种不同的核酸载体——siRNA 和编码 shRNA 的 pDNA。通过针对细胞因子 TNFα 的 RNAi，我们在两种疾病模型中均显示出有效的抗炎效果，并观察到疾病症状减轻。我们的结果突出了我们的转染载体在肺部基因治疗中的潜力。
