Sun Man, Zhang Huan, Liu Jiayi, Chen Jiayi, Cui Yaxin, Wang Simiao, Zhang Xiangyu, Yang Zhaogang
School of Life Sciences, Jilin University, Changchun, 130012, People's Republic of China.
Department of General Surgery, Sir Run Run Shaw Hospital, College of Medicine, Zhejiang University, Hangzhou, 310020, People's Republic of China.
Int J Nanomedicine. 2024 Mar 6;19:2241-2264. doi: 10.2147/IJN.S446224. eCollection 2024.
Recently, gene therapy has become a subject of considerable research and has been widely evaluated in various disease models. Though it is considered as a stand-alone agent for COVID-19 vaccination, gene therapy is still suffering from the following drawbacks during its translation from the bench to the bedside: the high sensitivity of exogenous nucleic acids to enzymatic degradation; the severe side effects induced either by exogenous nucleic acids or components in the formulation; and the difficulty to cross the barriers before reaching the therapeutic target. Therefore, for the successful application of gene therapy, a safe and reliable transport vector is urgently needed. Extracellular vesicles (EVs) are the ideal candidate for the delivery of gene drugs owing to their low immunogenicity, good biocompatibility and low toxicity. To better understand the properties of EVs and their advantages as gene drug delivery vehicles, this review covers from the origin of EVs to the methods of EVs generation, as well as the common methods of isolation and purification in research, with their pros and cons discussed. Meanwhile, the engineering of EVs for gene drugs is also highlighted. In addition, this paper also presents the progress in the EVs-mediated delivery of microRNAs, small interfering RNAs, messenger RNAs, plasmids, and antisense oligonucleotides. We believe this review will provide a theoretical basis for the development of gene drugs.
近年来,基因治疗已成为大量研究的主题,并已在各种疾病模型中得到广泛评估。尽管基因治疗被视为COVID-19疫苗接种的一种独立手段,但在从实验室到临床的转化过程中,基因治疗仍存在以下缺点:外源核酸对酶降解高度敏感;外源核酸或制剂中的成分会引发严重的副作用;以及在到达治疗靶点之前难以跨越各种屏障。因此,为了基因治疗的成功应用,迫切需要一种安全可靠的转运载体。细胞外囊泡(EVs)因其低免疫原性、良好的生物相容性和低毒性,是基因药物递送的理想候选者。为了更好地了解细胞外囊泡的特性及其作为基因药物递送载体的优势,本综述涵盖了从细胞外囊泡的起源到其产生方法,以及研究中常用的分离和纯化方法,并讨论了它们的优缺点。同时,还重点介绍了用于基因药物的细胞外囊泡工程。此外,本文还介绍了细胞外囊泡介导的微小RNA、小干扰RNA、信使RNA、质粒和反义寡核苷酸递送的研究进展。我们相信本综述将为基因药物的开发提供理论依据。
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