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Science DOI:10.1126/science.abg6155

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

Publication TypeJournal Article
Year of Publication2021
AuthorsSegel, M, Lash, B, Song, J, Ladha, A, Liu, CC, Jin, X, Mekhedov, SL, Macrae, RK, Koonin, EV, Zhang, F
JournalScience
Volume373
Issue6557
Pages882-889
Date Published2021 08 20
ISSN1095-9203
KeywordsAnimals, Apoptosis Regulatory Proteins, Capsid, Cell Line, DNA-Binding Proteins, Extracellular Vesicles, Gene Editing, Genetic Vectors, Humans, Mice, Neurons, Protein Domains, Retroelements, RNA, Messenger, RNA-Binding Proteins, Transfection, Untranslated Regions, Up-Regulation
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.

DOI10.1126/science.abg6155
Pubmed

http://www.ncbi.nlm.nih.gov/pubmed/34413232?dopt=Abstract

Alternate JournalScience
PubMed ID34413232
Grant ListR01 HG009761 / HG / NHGRI NIH HHS / United States
/ HHMI / Howard Hughes Medical Institute / United States