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

Science
Authors
Keywords
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 '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.

Year of Publication
2021
Journal
Science
Volume
373
Issue
6557
Pages
882-889
Date Published
2021 08 20
ISSN
1095-9203
DOI
10.1126/science.abg6155
PubMed ID
34413232
Links
Grant list
R01 HG009761 / HG / NHGRI NIH HHS / United States
HHMI / Howard Hughes Medical Institute / United States