Cellular microvesicle pathways can be targeted to transfer genetic information between non-immune cells

Amy Skinner, S. Lee O'Neil, Peter Kurre

Research output: Contribution to journalArticle

16 Citations (Scopus)

Abstract

Eukaryotic cell communication is based on protein signaling cascades that require direct cell-cell apposition, or receptor engagement by secreted molecules. The transmission of genetic information is thought to be uncommon, apart from recent reports of exosomal RNA transfer in immune and glioblastoma cells. We wished to examine if existing microvesicle pathways could be directly targeted for the horizontal transfer of RNA genomes in less specialized cell types. Using replication-deficient retrovirus vector, studies herein confirm that a range of cells routinely sequester a small population of these RNA genomes in a non-canonical compartment, refractory to antibody neutralization and unaffected by specific pharmacological inhibition of pathways involved in conventional viral trafficking. Our experiments further reveal the cytoplasmic colocalization of vector genomes with tetraspanin proteins as well as the PI-3-kinase sensitive trafficking and subsequent transmission to 2° targets. Collectively, our results indicate a scalable process whereby cells route vector genomes to multivesicular bodies (MVB) for cytoplasmic trafficking and exosomal release. Our findings imply that cells can serve to deliver recombinant payload, targeted for the stable genetic modification of 2° target cells.

Original languageEnglish (US)
Article numbere6219
JournalPLoS One
Volume4
Issue number7
DOIs
StatePublished - Jul 13 2009

Fingerprint

Genes
Transfer RNA
Genome
cells
transfer RNA
genome
Phosphatidylinositol 3-Kinases
Refractory materials
Proteins
Retroviridae
RNA
Multivesicular Bodies
cell communication
Molecules
Antibodies
Communication
phosphatidylinositol 3-kinase
Eukaryotic Cells
Glioblastoma
genetic engineering

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Cellular microvesicle pathways can be targeted to transfer genetic information between non-immune cells. / Skinner, Amy; O'Neil, S. Lee; Kurre, Peter.

In: PLoS One, Vol. 4, No. 7, e6219, 13.07.2009.

Research output: Contribution to journalArticle

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