期刊
SCIENCE
卷 373, 期 6557, 页码 882-+出版社
AMER ASSOC ADVANCEMENT SCIENCE
DOI: 10.1126/science.abg6155
关键词
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资金
- Simons Foundation
- National Institutes of Health Intramural Research Program
- National Institutes of Health [1R01-HG009761, 1DP1-HL141201]
- Howard Hughes Medical Institute
- Open Philanthropy
- G. Harold and Leila Y. Mathers Charitable Foundation
- Edward Mallinckrodt, Jr. Foundation
- Poitras Center for Psychiatric Disorders Research at MIT
- Hock E. Tan and K. Lisa Yang Center for Autism Research at MIT
- Yang-Tan Center for Molecular Therapeutics at MIT
Eukaryotic genomes contain domesticated genes from integrating viruses and mobile genetic elements, including mammalian Gag homologs and PEG10, which can be used for RNA delivery. The development of selective endogenous encapsidation for cellular delivery (SEND) using PEG10 demonstrates its potential as an efficient therapeutic delivery modality.
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.
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