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.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis Regulatory Proteins / chemistry
  • Apoptosis Regulatory Proteins / genetics
  • Apoptosis Regulatory Proteins / metabolism*
  • Capsid / metabolism
  • Cell Line
  • DNA-Binding Proteins / chemistry
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / metabolism*
  • Extracellular Vesicles / metabolism
  • Gene Editing
  • Genetic Vectors
  • Humans
  • Mice
  • Neurons / metabolism
  • Protein Domains
  • RNA, Messenger / genetics*
  • RNA, Messenger / metabolism*
  • RNA-Binding Proteins / chemistry
  • RNA-Binding Proteins / genetics
  • RNA-Binding Proteins / metabolism*
  • Retroelements
  • Transfection
  • Untranslated Regions
  • Up-Regulation


  • Apoptosis Regulatory Proteins
  • DNA-Binding Proteins
  • PEG10 protein, human
  • Peg10 protein, mouse
  • RNA, Messenger
  • RNA-Binding Proteins
  • Retroelements
  • Untranslated Regions