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

被引：291

作者：

Segel, Michael ^{[1
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,3
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,5
]}

Lash, Blake ^{[1
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,4
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]}

Song, Jingwei ^{[1
,2
,3
,4
,5
]}

Ladha, Alim ^{[1
,2
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,5
]}

Liu, Catherine C. ^{[1
,2
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,5
,6
]}

Jin, Xin ^{[2
,3
,4
,7
]}

Mekhedov, Sergei L. ^{[8
]}

Macrae, Rhiannon K. ^{[1
,2
,3
,4
,5
]}

Koonin, Eugene V. ^{[8
]}

Zhang, Feng ^{[1
,2
,3
,4
,5
]}

机构：

[1] Howard Hughes Med Inst, Cambridge, MA 02139 USA

[2] Broad Inst MIT & Harvard, Cambridge, MA 02142 USA

[3] MIT, McGovern Inst Brain Res, Cambridge, MA 02139 USA

[4] MIT, Dept Brain & Cognit Sci, Cambridge, MA 02139 USA

[5] MIT, Dept Biol Engn, Cambridge, MA 02139 USA

[6] MIT, Dept Biol, Cambridge, MA 02139 USA

[7] Harvard Univ, Cambridge, MA 02138 USA

[8] NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bldg 10, Bethesda, MD 20892 USA

来源：

SCIENCE | 2021年 / 373卷 / 6557期

基金：

美国国家卫生研究院;

关键词：

TRANSPOSABLE ELEMENTS; GAG PROTEIN; GENE; RETROTRANSPOSON; GENOME; ARC; SEQ; IDENTIFICATION; EVOLUTION; INSIGHTS;

D O I：

10.1126/science.abg6155

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

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.

引用

页码：882 / +

页数：63

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