Härk Heleri H, Porosk Ly, de Mello Lucas R, Arukuusk Piret, da Silva Emerson R, Kurrikoff Kaido
Institute of Technology, University of Tartu, Nooruse 1, 50411 Tartu, Estonia.
Departamento de Biofisica, Universidade Federal de São Paulo, São Paulo 04023-062, Brazil.
Pharmaceutics. 2023 Mar 9;15(3):883. doi: 10.3390/pharmaceutics15030883.
Despite numerous efforts over the last three decades, nucleic acid-based therapeutics still lack delivery platforms in the clinical stage. Cell-penetrating peptides (CPPs) may offer solutions as potential delivery vectors. We have previously shown that designing a "kinked" structure in the peptide backbone resulted in a CPP with efficient in vitro transfection properties. Further optimization of the charge distribution in the C-terminal part of the peptide led to potent in vivo activity with the resultant CPP NickFect55 (NF55). Currently, the impact of the linker amino acid was further investigated in the CPP NF55, with the aim to discover potential transfection reagents for in vivo application. Taking into account the expression of the delivered reporter in the lung tissue of mice, and the cell transfection in the human lung adenocarcinoma cell line, the new peptides NF55-Dap and NF55-Dab* have a high potential for delivering nucleic acid-based therapeutics to treat lung associated diseases, such as adenocarcinoma.
尽管在过去三十年中进行了大量努力，但基于核酸的疗法在临床阶段仍然缺乏递送平台。细胞穿透肽（CPPs）作为潜在的递送载体可能提供解决方案。我们之前已经表明，在肽主链中设计一个“扭结”结构会产生一种具有高效体外转染特性的CPP。对肽C末端部分电荷分布的进一步优化导致了具有体内活性的强效CPP NickFect55（NF55）。目前，在CPP NF55中进一步研究了连接氨基酸的影响，目的是发现用于体内应用的潜在转染试剂。考虑到递送的报告基因在小鼠肺组织中的表达以及在人肺腺癌细胞系中的细胞转染情况，新的肽NF55-Dap和NF55-Dab*在递送基于核酸的疗法以治疗肺部相关疾病（如腺癌）方面具有很高的潜力。
