Kumar Lalit, Verma Shivani, Vaidya Bhuvaneshwar, Gupta Vivek
School of Pharmacy, Keck Graduate Institute, Claremont, CA 91711.
Curr Pharm Des. 2015;21(31):4556-65. doi: 10.2174/138161282131151013190112.
Various cells of the human physiological system have the capability to release extracellular vesicles (EVs) involved in intercellular transport of proteins and nucleic acids. Exosomes are a subtype of extracellular vesicles having their origin through endocytic pathway. While being involved in intercellular transport of macromolecules, exosomes, due to their presence in several body fluids, can also be utilized as a system to commute RNA molecules and proteins in the body. Recent advances in gene therapy have provided a new outlook in disease therapeutics by modulation of gene expression using oligonucleotide based approach and exosomes have been reported a potential carrier for nucleic acid based therapeutic moieties. In recent years, small interfering RNA (siRNA) has emerged as promising therapeutic alternative for diseases with gene-based pathophysiology, however poor bioavailability limits its therapeutic potential. For effective delivery and enhancement of bioavailability of siRNA, several carriers including dendrimers, liposomes, siRNA conjugates, and siRNA aptamer chimeras, to name a few, have been explored. Exosomes can be considered a promising carrier for effective delivery of siRNA due to their existence in body's endogenous system and high tolerance. The present review focuses on delivering knowledge about exosomes, siRNA, and capability of exosomes to act as natural carriers for siRNA delivery.
人体生理系统的各种细胞都有能力释放参与蛋白质和核酸细胞间运输的细胞外囊泡（EVs）。外泌体是细胞外囊泡的一种亚型，其起源于内吞途径。外泌体在参与大分子的细胞间运输时，由于它们存在于多种体液中，也可作为一种在体内转运RNA分子和蛋白质的系统。基因治疗的最新进展通过基于寡核苷酸的方法调节基因表达，为疾病治疗提供了新的前景，并且外泌体已被报道为基于核酸的治疗部分的潜在载体。近年来，小干扰RNA（siRNA）已成为具有基于基因的病理生理学疾病的有前景的治疗替代物，然而其较差的生物利用度限制了其治疗潜力。为了有效递送和提高siRNA的生物利用度，人们探索了几种载体，包括树枝状聚合物、脂质体、siRNA缀合物和siRNA适配体嵌合体等。由于外泌体存在于人体的内源性系统中且耐受性高，因此可被视为有效递送siRNA的有前景的载体。本综述着重介绍有关外泌体、siRNA以及外泌体作为siRNA递送天然载体的能力的知识。
