美国麻省理工学院张锋研究组发现，哺乳动物逆转录病毒样蛋白PEG10包装自己的mRNA，并可作为mRNA的传递方式。2021年8月20日出版的《科学》杂志发表了这项成果。

研究人员表示，真核生物基因组包含来自整合病毒和移动遗传元素的驯化基因。其中包括长末端重复（LTR）逆转录基因和逆转录病毒的外壳蛋白（被称为Gag）的同源物。

研究人员确定了几个哺乳动物的Gag同源物，它们形成病毒样颗粒，还有一个LTR逆转录基因同源物PEG10，它优先结合并促进其自身信使RNA（mRNA）的囊泡分泌。结果表明，PEG10的mRNA货物可以通过用Peg10的非翻译区对感兴趣的基因进行侧翼重编程。利用这种可重编程性，研究人员通过对小鼠和人类PEG10进行工程设计，开发了选择性内源性包膜的细胞传递（SEND），从而包装、分泌和传递特定的RNA。这些结果表明，SEND是一个模块化的平台，适合发展为一种高效的治疗递送方式。

附：英文原文

Title: Mammalian retrovirus-like protein PEG10 packages its own mRNA and can be pseudotyped for mRNA delivery

Author: Michael Segel, Blake Lash, Jingwei Song, Alim Ladha, Catherine C. Liu, Xin Jin, Sergei L. Mekhedov, Rhiannon K. Macrae, Eugene V. Koonin, Feng Zhang

Issue&Volume: 2021/08/20

Abstract: Eukaryotic genomes contain domesticated genes from integrating viruses and mobile genetic elements. Among these are homologs of the capsid protein (known as Gag) of long terminal repeat (LTR) retrotransposons and retroviruses. We identified several mammalian Gag homologs that form virus-like particles and one LTR retrotransposon homolog, PEG10, that preferentially binds and facilitates vesicular secretion of its own messenger RNA (mRNA). We showed that the mRNA cargo of PEG10 can be reprogrammed by flanking genes of interest with Peg10’s untranslated regions. Taking advantage of this reprogrammability, we developed selective endogenous encapsidation for cellular delivery (SEND) by engineering both mouse and human PEG10 to package, secrete, and deliver specific RNAs. Together, these results demonstrate that SEND is a modular platform suited for development as an efficient therapeutic delivery modality.

DOI: 10.1126/science.abg6155

Source: https://science.sciencemag.org/content/373/6557/882