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Author Correction: GAPDH controls extracellular vesicle biogenesis and enhances the therapeutic potential of EV mediated siRNA delivery to the brain
- Source :
- Nature Communications, Nature Communications, Vol 12, Iss 1, Pp 1-1 (2021)
- Publication Year :
- 2021
- Publisher :
- Springer Science and Business Media LLC, 2021.
-
Abstract
- 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.
- Subjects :
- RNAi therapy
Science
General Physics and Astronomy
Phosphatidylserines
General Biochemistry, Genetics and Molecular Biology
Extracellular Vesicles
Drug Delivery Systems
Cell Line, Tumor
Animals
Humans
RNA, Small Interfering
Author Correction
Huntingtin Protein
Multidisciplinary
Brain
Glyceraldehyde-3-Phosphate Dehydrogenases
Mesenchymal Stem Cells
General Chemistry
Mice, Inbred C57BL
Disease Models, Animal
HEK293 Cells
Huntington Disease
Extracellular signalling molecules
HeLa Cells
Protein Binding
Subjects
Details
- ISSN :
- 20411723
- Volume :
- 12
- Database :
- OpenAIRE
- Journal :
- Nature Communications
- Accession number :
- edsair.doi.dedup.....a1039086ff9d4953584fa35e01a746ff