Search: onr:"swepub:oai:prod.swepub.kib.ki.se:148255629" >
GAPDH controls extr...
GAPDH controls extracellular vesicle biogenesis and enhances the therapeutic potential of EV mediated siRNA delivery to the brain
-
Dar, GH (author)
-
Mendes, CC (author)
-
Kuan, WL (author)
-
show more...
-
Speciale, AA (author)
-
Conceicao, M (author)
-
- Gorgens, A (author)
- Karolinska Institutet
-
Uliyakina, I (author)
-
Lobo, MJ (author)
-
Lim, WF (author)
-
- El Andaloussi, S (author)
- Karolinska Institutet
-
Mager, I (author)
-
Roberts, TC (author)
-
Barker, RA (author)
-
Goberdhan, DCI (author)
-
Wilson, C (author)
-
Wood, MJA (author)
-
show less...
-
(creator_code:org_t)
- 2021-11-18
- 2021
- English.
-
In: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 12:1, s. 6666-
- Related links:
-
https://www.nature.c...
-
show more...
-
http://kipublication...
-
https://doi.org/10.1...
-
show less...
Abstract
Subject headings
Close
- Extracellular vesicles (EVs) are biological nanoparticles with important roles in intercellular communication, and potential as drug delivery vehicles. Here we demonstrate a role for the glycolytic enzyme glyceraldehyde-3-phosphate dehydrogenase (GAPDH) in EV assembly and secretion. We observe high levels of GAPDH binding to the outer surface of EVs via a phosphatidylserine binding motif (G58), which promotes extensive EV clustering. Further studies in a Drosophila EV biogenesis model reveal that GAPDH is required for the normal generation of intraluminal vesicles in endosomal compartments, and promotes vesicle clustering. Fusion of the GAPDH-derived G58 peptide to dsRNA-binding motifs enables highly efficient loading of small interfering RNA (siRNA) onto the EV surface. Such vesicles efficiently deliver siRNA to multiple anatomical regions of the brain in a Huntington’s disease mouse model after systemic injection, resulting in silencing of the huntingtin gene in different regions of the brain.
Publication and Content Type
- ref (subject category)
- art (subject category)
Find in a library
To the university's database
- By the author/editor
-
Dar, GH
-
Mendes, CC
-
Kuan, WL
-
Speciale, AA
-
Conceicao, M
-
Gorgens, A
-
show more...
-
Uliyakina, I
-
Lobo, MJ
-
Lim, WF
-
El Andaloussi, S
-
Mager, I
-
Roberts, TC
-
Barker, RA
-
Goberdhan, DCI
-
Wilson, C
-
Wood, MJA
-
show less...
- Articles in the publication
-
Nature communica ...
- By the university
-
Karolinska Institutet