Harnessing genetically engineered cell membrane-derived vesicles as biotherapeutics

Xiaohong Li, Yuting Wei, Zhirang Zhang, Xudong Zhang
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Abstract

Cell membrane-derived vesicles (CMVs) are particles generated from living cells, including extracellular vesicles (EVs) and artificial extracellular vesicles (aEVs) prepared from cell membranes. CMVs possess considerable potential in drug delivery, regenerative medicine, immunomodulation, disease diagnosis, etc . owing to their stable lipid bilayer structure, favorable biocompatibility, and low toxicity. Although the majority of CMVs inherit certain attributes from the original cells, it is still difficult to execute distinct therapeutic functions, such as organ targeting, signal regulation, and exogenous biotherapeutic supplementation. Hence, engineering CMVs by genetic engineering, chemical modification, and hybridization is a promising way to endow CMVs with specific functions and open up novel vistas for applications. In particular, there is a growing interest in genetically engineered CMVs harnessed to exhibit biotherapeutics. Herein, we outline the preparation strategies and their characteristics for purifying CMVs. Additionally, we review the advances of genetically engineered CMVs utilized to target organs, regulate signal transduction, and deliver biomacromolecules and chemical drugs. Furthermore, we also summarize the emerging therapeutic applications of genetically engineered CMVs in addressing tumors, diabetes, systemic lupus erythematosus, and cardiovascular diseases.
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利用基因工程细胞膜衍生囊泡作为生物治疗药物
细胞膜衍生囊泡(CMVs)是由活细胞产生的颗粒,包括细胞外囊泡(EVs)和由细胞膜制备的人工细胞外囊泡(aEVs)。由于其稳定的脂质双分子层结构、良好的生物相容性和低毒性,CMVs 在药物输送、再生医学、免疫调节、疾病诊断等方面具有相当大的潜力。虽然大多数 CMVs 都继承了原始细胞的某些特性,但仍难以实现独特的治疗功能,如器官靶向、信号调节和外源生物治疗补充。因此,通过基因工程、化学修饰和杂交等方法对 CMV 进行工程化改造,是赋予 CMV 特定功能并为其应用开辟新前景的一种可行方法。特别是,人们对利用基因工程 CMV 进行生物治疗的兴趣与日俱增。在此,我们概述了纯化 CMV 的制备策略及其特点。此外,我们还回顾了基因工程 CMV 在靶向器官、调节信号转导、递送生物大分子和化学药物方面的进展。此外,我们还总结了基因工程 CMV 在治疗肿瘤、糖尿病、系统性红斑狼疮和心血管疾病方面的新兴应用。
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