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

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

  • Science. 2021 Aug 20;373(6557):882-889. doi: 10.1126/science.abg6155.
Michael Segel 1 2 3 4 5,  Blake Lash 1 2 3 4 5,  Jingwei Song 1 2 3 4 5,  Alim Ladha 1 2 3 4 5,  Catherine C Liu 6 1 2 3 4 5,  Xin Jin 2 3 4 7,  Sergei L Mekhedov 8,  Rhiannon K Macrae 1 2 3 4 5,  Eugene V Koonin 8,  Feng Zhang 1 2 3 4 5
Affiliations

Affiliations

  • 1 Howard Hughes Medical Institute, Cambridge, MA 02139, USA.
  • 2 Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
  • 3 McGovern Institute for Brain Research, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
  • 4 Department of Brain and Cognitive Science, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
  • 5 Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
  • 6 Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
  • 7 Society of Fellows, Harvard University, Cambridge, MA 02138 USA.
  • 8 National Center for Biotechnology Information, National Library of Medicine, National Institutes of Health, Bethesda, MD 20894, USA.
PMID: 34413232 DOI: 10.1126/science.abg6155
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 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.

Figures