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DOI | 10.1126/science.abg6155 |
Mammalian retrovirus-like protein PEG10 packages its own mRNA and can be pseudotyped for mRNA delivery | |
Michael Segel; Blake Lash; Jingwei Song; Alim Ladha; Catherine C. Liu; Xin Jin; Sergei L. Mekhedov; Rhiannon K. Macrae; Eugene V. Koonin; Feng Zhang | |
2021-08-20 | |
发表期刊 | Science
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出版年 | 2021 |
英文摘要 | Retroviruses and retroelements have inserted their genetic code into mammalian genomes throughout evolution. Although many of these integrated virus-like sequences pose a threat to genomic integrity, some have been retooled by mammalian cells to perform essential roles in development. Segel et al. found that one of these retroviral-like proteins, PEG10, directly binds to and secretes its own mRNA in extracellular virus–like capsids. These virus-like particles were then pseudotyped with fusogens to deliver functional mRNA cargos to mammalian cells. This potentially provides an endogenous vector for RNA-based gene therapy. Science , abg6155, this issue p. [882][1] 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. [1]: /lookup/doi/10.1126/science.abg6155 |
领域 | 气候变化 ; 资源环境 |
URL | 查看原文 |
引用统计 | |
文献类型 | 期刊论文 |
条目标识符 | http://119.78.100.173/C666/handle/2XK7JSWQ/336029 |
专题 | 气候变化 资源环境科学 |
推荐引用方式 GB/T 7714 | Michael Segel,Blake Lash,Jingwei Song,et al. Mammalian retrovirus-like protein PEG10 packages its own mRNA and can be pseudotyped for mRNA delivery[J]. Science,2021. |
APA | Michael Segel.,Blake Lash.,Jingwei Song.,Alim Ladha.,Catherine C. Liu.,...&Feng Zhang.(2021).Mammalian retrovirus-like protein PEG10 packages its own mRNA and can be pseudotyped for mRNA delivery.Science. |
MLA | Michael Segel,et al."Mammalian retrovirus-like protein PEG10 packages its own mRNA and can be pseudotyped for mRNA delivery".Science (2021). |
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