Menzies Health Institute Queensland, School of Pharmacy and Medical Science, Griffith University, Gold Coast Campus, Southport, QLD 4222, Australia.
Departments of Molecular and Comparative Pathobiology and Neurology, and Richman Family Precision Medicine Center of Excellence in Alzheimer's Disease, Johns Hopkins University, Baltimore, MD 21205, USA.
Mol Ther. 2023 May 3;31(5):1225-1230. doi: 10.1016/j.ymthe.2023.01.021. Epub 2023 Jan 25.
Extracellular vesicles (EVs) are esteemed as a promising delivery vehicle for various genetic therapeutics. They are relatively inert, non-immunogenic, biodegradable, and biocompatible. At least in rodents, they can even transit challenging bodily hurdles such as the blood-brain barrier. Constitutively shed by all cells and with the potential to interact specifically with neighboring and distant targets, EVs can be engineered to carry and deliver therapeutic molecules such as proteins and RNAs. EVs are thus emerging as an elegant in vivo gene therapy vector. Deeper understanding of basic EV biology-including cellular production, EV loading, systemic distribution, and cell delivery-is still needed for effective harnessing of these endogenous cellular nanoparticles as next-generation nanodelivery tools. However, even a perfect EV product will be challenging to produce at clinical scale. In this regard, we propose that vector transduction technologies can be used to convert cells either ex vivo or directly in vivo into EV factories for stable, safe modulation of gene expression and function. Here, we extrapolate from the current EV state of the art to a bright potential future using EVs to treat genetic diseases that are refractory to current therapeutics.
细胞外囊泡 (EVs) 被认为是一种很有前途的基因治疗载体，可用于各种基因治疗。它们相对惰性、非免疫原性、可生物降解且生物相容性好。至少在啮齿动物中，它们甚至可以穿越血脑屏障等具有挑战性的身体障碍。EVs 由所有细胞持续分泌，具有与邻近和远处靶标特异性相互作用的潜力，可以对其进行工程改造，以携带和递送治疗性分子，如蛋白质和 RNA。因此，EVs 正在成为一种优雅的体内基因治疗载体。为了有效利用这些内源性细胞纳米颗粒作为下一代纳米递药工具，还需要更深入地了解 EV 生物学的基础，包括细胞产生、EV 装载、系统分布和细胞递送。然而，即使是完美的 EV 产品也难以在临床规模上生产。在这方面，我们提出可以使用载体转导技术将细胞在体外或体内直接转化为 EV 工厂，从而稳定、安全地调节基因表达和功能。在这里，我们从当前 EV 技术的现状推断出一个光明的未来，即使用 EV 治疗目前治疗方法无效的遗传性疾病。
