Cell Penetrating Peptide Conjugated Chitosan for Enhanced Delivery of Nucleic Acid.
Cell Penetrating Peptide Conjugated Chitosan for Enhanced Delivery of Nucleic Acid.
复制标题
DOI：
10.3390/ijms161226142
复制
发表时间：
2015-12-04
影响因子：
5.6
通讯作者：
Singh J
中科院分区：
文献类型：
--
作者：
Layek B;Lipp L;Singh J
基因治疗是一种新兴的治疗策略，用于治愈或治疗一系列遗传性疾病。然而，基因治疗的进步在很大程度上依赖于有效基因载体的设计，该载体可以将基因货物传递到所需的细胞群中。在各种非病毒基因传递系统中，基于壳聚糖的载体因其高阳离子电荷密度、优异的生物相容性、几乎不存在的细胞毒性、可忽略的免疫反应以及理想的化学缀合能力而受到越来越多的关注。然而，基于壳聚糖的载体的一个主要缺点是细胞摄取较差，导致转染效率不足。细胞穿透肽（CPP）以安全的方式将不同的货物转运到多种细胞和组织类型的内在特征表明它们可以与壳聚糖缀合以提高其转染效率。在这篇综述中，我们简要讨论了 CPP 及其分类，以及促进细胞摄取 CPP 和货物结合物的主要机制。我们还讨论了使用 CPP 缀合的基于壳聚糖的载体递送核酸的巨大改进，特别强调质粒 DNA 和小干扰 RNA。
Gene therapy is an emerging therapeutic strategy for the cure or treatment of a spectrum of genetic disorders. Nevertheless, advances in gene therapy are immensely reliant upon design of an efficient gene carrier that can deliver genetic cargoes into the desired cell populations. Among various nonviral gene delivery systems, chitosan-based carriers have gained increasing attention because of their high cationic charge density, excellent biocompatibility, nearly nonexistent cytotoxicity, negligible immune response, and ideal ability to undergo chemical conjugation. However, a major shortcoming of chitosan-based carriers is their poor cellular uptake, leading to inadequate transfection efficiency. The intrinsic feature of cell penetrating peptides (CPPs) for transporting diverse cargoes into multiple cell and tissue types in a safe manner suggests that they can be conjugated to chitosan for improving its transfection efficiency. In this review, we briefly discuss CPPs and their classification, and also the major mechanisms contributing to the cellular uptake of CPPs and cargo conjugates. We also discuss immense improvements for the delivery of nucleic acids using CPP-conjugated chitosan-based carriers with special emphasis on plasmid DNA and small interfering RNA.