GAPDH controls extracellular vesicle biogenesis and enhances the therapeutic potential of EV mediated siRNA delivery to the brain.
Dar, Ghulam Hassan
Mendes, Cláudia C
Lobo, Miguel J
Springer Science and Business Media LLC
MetadataShow full item record
Dar, G. H., Mendes, C. C., Kuan, W., Speciale, A. A., Conceição, M., Görgens, A., Uliyakina, I., et al. (2021). GAPDH controls extracellular vesicle biogenesis and enhances the therapeutic potential of EV mediated siRNA delivery to the brain.. Nat Commun, 12 (1) https://doi.org/10.1038/s41467-021-27056-3
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.
Article, /631/61/391/3932, /631/80/86/820, /13, /13/89, /14, /38, /42, /42/89, /59, /59/5, /64, /64/60, article
Medical Research Council (MR/M007715/1)
External DOI: https://doi.org/10.1038/s41467-021-27056-3
This record's URL: https://www.repository.cam.ac.uk/handle/1810/330877
Recommended or similar items
The current recommendation prototype on the Apollo Repository will be turned off on 03 February 2023. Although the pilot has been fruitful for both parties, the service provider IKVA is focusing on horizon scanning products and so the recommender service can no longer be supported. We recognise the importance of recommender services in supporting research discovery and are evaluating offerings from other service providers. If you would like to offer feedback on this decision please contact us on: firstname.lastname@example.org