Prototype mouse models for researching SEND-based mRNA delivery and gene therapy.
Prototype mouse models for researching SEND-based mRNA delivery and gene therapy.
复制标题
用于研究基于 SEND 的 mRNA 传递和基因治疗的原型小鼠模型。
DOI：
10.1038/s41596-022-00721-7
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发表时间：
2022
期刊：
影响因子：
14.8
通讯作者：
Ohtsuka,Masato
中科院分区：
文献类型：
--
作者：
Gurumurthy,ChannabasavaiahB;Quadros,RolenM;Ohtsuka,Masato
基因疗法——一种治疗由缺陷基因引起的疾病的方法——面临的主要挑战之一是缺乏将健康基因复制到目标组织和细胞的技术。一些常用的方法包括病毒载体或涂覆治疗性核酸与脂基纳米粒子通过细胞膜，但这些技术的成功有限。一种革命性的工具，CRISPR-Cas基因编辑系统，提供了巨大的希望，但它也存在传输问题。另一种名为“SEND”的工具（即“选择性内源性细胞递送封装”）似乎提供了更好的解决方案。SEND系统使用内源性遗传成分包装mRNA货物，通过病毒样颗粒（vlp）将其传递到其他细胞。如果SEND的内源性成分可以被重新利用以产生含有治疗货物的VLPs，那么SEND- vlp工具作为基因治疗工具具有巨大的潜力。然而，这个新发现的现象的几个方面还没有完全理解。基因工程小鼠（GEM）模型以可控和诱导的方式表达SEND组分的不同组合，可以作为有价值的工具来更多地了解该工具并将其重新用于基因治疗应用。在这方面，我们讨论了GEM模型和小鼠分子遗传学工具如何用于SEND-VLP研究。
One of the major challenges of gene therapy—an approach to treat diseases caused by faulty genes—is a lack of technologies that deliver healthy gene copies to target tissues and cells. Some commonly used approaches include viral vectors or coating therapeutic nucleic acids with lipid-based nanoparticles to pass through cell membranes, but these technologies have had limited success. A revolutionary tool, the CRISPR–Cas gene-editing system, offers tremendous promise, but it too suffers from problems with delivery. Another tool, called ‘SEND’ (for ‘selective endogenous encapsidation for cellular delivery’), seems to offer a better solution. The SEND system uses endogenous genetic components to package mRNA cargoes to deliver them to other cells via virus-like particles (VLPs). The SEND-VLP tool has enormous potential as a gene-therapy tool, if the endogenous components of SEND can be repurposed to produce VLPs containing therapeutic cargoes. However, several aspects of this newly identified phenomenon are not yet fully understood. Genetically engineered mouse (GEM) models, expressing different combinations of SEND components in a controllable and inducible fashion, could serve as valuable tools to understand more about this tool and to repurpose it for gene-therapy applications. In this Perspective, we discuss how GEM models and mouse molecular genetics tools could be used for SEND-VLP research.