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.

真核基因组包含来自整合病毒和移动遗传元件的驯化基因。其中包括长末端重复 (LTR) 反转录转座子和反转录病毒的衣壳蛋白（称为 Gag）的同源物。我们鉴定了几种形成病毒样颗粒的哺乳动物 Gag 同源物和一种 LTR 反转录转座子同源物 PEG10，它优先结合并促进其自身信使 RNA (mRNA) 的囊泡分泌。我们发现 PEG10 的 mRNA 货物可以通过用Peg10侧翼感兴趣的基因来重新编程的未翻译区域。利用这种可重编程性，我们通过设计小鼠和人类 PEG10 来包装、分泌和传递特定的 RNA，开发了用于细胞传递的选择性内源性封装 (SEND)。总之，这些结果表明，SEND 是一个模块化平台，适合开发为一种有效的治疗递送方式。