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Genetic communication between cells via exosome vesicles, the use of exosomes for delivery of therapeutic RNAs to cells

Exosomes are small vesicles (30-150 nm in diameter) secreted by almost all cell types under normal as well as pathological conditions. They have been detected in many biological fluids, as well as supernatants of cultured cells. These vesicles are originated from endocytic pathway, when late endosomes fuse with plasma membrane and release internal vesicles to the extracellular milieu (1).
In 2007, we revealed that exosomes from various origins contain a substantial amount of RNA, mainly mRNA and microRNA but contained no or little ribosomal RNA (2). Moreover, we discovered that the exosome vesicles are capable to donate their RNA-content to other cells.

Fig. 1) a hypothetical mechanism for the transfer of RNA into exosomes during their biosynthesis. We suggest that a number of RNA-binding proteins (RBPs) recognize and transfer certain RNAs into intraluminal of endosomes, during biosynthesis of exosomes.


Since exosomes naturally transport genetic materials between cells, we hypothesized that these vesicles - derived from human materials - might be an ideal candidate as delivery vehicle, to deliver therapeutic RNA-molecules to cells/ organs. In order for the exosomes to act as vehicle for delivery of therapeutic RNAs to cells, the exogenous nucleic acids initially need to be introduced into these vesicles.
Our current studies primarily are focused on further understanding the mechanisms by which cells send RNA molecules to each other via exosomes. We have shown that exosomes contain a subset of RNA is released into the extracellular environment via secretion of exosomes. However, the mechanism by which this subset of RNAs are loaded into exosomes, maintained, and transferred to other cells remains unknown. We hypothesized that these RNAs are packaged into exosomes (translocated from cytosol into intraluminal vesicles of endosomes) through the action of specific RNA-binding proteins.

Group members:
Dr. Marco Maugeri (PostDoc), Dr. Alexandros Papadimitriou (PostDoc), Dr. Elena Garre (PostDoc)

References:

  1. Fevrier, B. and Raposo, G. (2004) Exosomes: endosomal-derived vesicles shipping extracellular messages. Current opinion in cell biology, 16, 415-421.
  2. Valadi, H., Ekstrom, K., Bossios, A., Sjostrand, M., Lee, J.J. and Lotvall, J.O. (2007) Exosome-mediated transfer of mRNAs and microRNAs is a novel mechanism of genetic exchange between cells. Nature cell biology, 9, 654-659.
     
Hadi Valadi

Kontaktinformation

Hadi Valadi

Box 480, 405 30 Göteborg

Besöksadress:
Guldhedsgatan 10A

Telefon:
031-342 33 36

Sidansvarig: kommunikation@medicine.gu.se|Sidan uppdaterades: 2017-05-31
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