Department of Chemical Engineering and Waterloo Institute for Nanotechnology, University of Waterloo, 200 University Avenue West, Waterloo, Ontario N2L 3G1, Canada.
Department of Chemical Engineering and Waterloo Institute for Nanotechnology, University of Waterloo, 200 University Avenue West, Waterloo, Ontario N2L 3G1, Canada; Key Laboratory of Chemical Additives for China National Light Industry, College of Chemistry and Chemical Engineering, Shaanxi University of Science and Technology, Xi'an 710021, China.
Adv Colloid Interface Sci. 2022 Apr;302:102638. doi: 10.1016/j.cis.2022.102638. Epub 2022 Mar 9.
In the past decades, the striking development of cationic polypeptides and cell-penetrating peptides (CPPs) tailored for small interfering RNA (siRNA) delivery has been fuelled by the conception of nuclear acid therapy and precision medicine. Owing to their amino acid compositions, inherent secondary structures as well as diverse geometrical shapes, peptides or peptide-containing polymers exhibit good biodegradability, high flexibility, and bio-functional diversity as nonviral siRNA vectors. Also, a variety of noncovalent nanocomplexes could be built via self-assembling and electrostatic interactions between cationic peptides and siRNAs. Although the peptide/siRNA nanocomplex-based RNAi therapies, STP705 and MIR-19, are under clinical trials, a guideline addressing the current bottlenecks of peptide/siRNA nanocomplex delivery is in high demand for future research and development. In this review, we present strategies for improving the safety and RNAi efficacy of noncovalent peptide/siRNA nanocomplexes in the treatment of genetic disorders. Through thorough analysis of those RNAi formulations using different delivery strategies, we seek to shed light on the rationale of peptide design and modification in constructing robust siRNA delivery systems, including targeted and co-delivery systems. Based on this, we provide a timely and comprehensive understanding of how to engineer biocompatible and efficient peptide-based siRNA vectors.
在过去的几十年中，由于核酸治疗和精准医学概念的出现，针对小干扰 RNA (siRNA) 递送而精心设计的阳离子多肽和细胞穿透肽 (CPP) 的惊人发展得到了推动。由于其氨基酸组成、固有二级结构以及多样的几何形状，肽或含肽聚合物作为非病毒 siRNA 载体表现出良好的生物降解性、高灵活性和生物功能多样性。此外，还可以通过阳离子肽和 siRNA 之间的自组装和静电相互作用构建各种非共价纳米复合物。尽管基于肽/siRNA 纳米复合物的 RNAi 疗法 STP705 和 MIR-19 正在临床试验中，但对于未来的研究和开发，需要制定解决肽/siRNA 纳米复合物递送当前瓶颈的指南。在这篇综述中，我们提出了改善非共价肽/siRNA 纳米复合物在治疗遗传疾病中的安全性和 RNAi 功效的策略。通过对使用不同递送策略的这些 RNAi 制剂进行深入分析，我们旨在阐明肽设计和修饰在构建稳健的 siRNA 递送系统（包括靶向和共递系统）中的原理。在此基础上，我们及时全面地了解如何设计生物相容性和高效的基于肽的 siRNA 载体。
