Edición de ARN mediante el reclutamiento de ADAR endógeno utilizando ARN largos para corregir las sustituciones de glicina en COL6-RD
Collagen VI-related dystrophies (COL6-RD) are commonly caused by dominant-negative pathogenic variants in the COL6A1,COL6A2 and COL6A3 genes, such as glycine substitutions of the conserved Gly-X-Y motives. For these mutations, allele-specific silencing approaches have been tested and have shown great promise but the final result, if perfectly working, is the expression of half the normal collagen VI protein level.
Gly substitutions are commonly caused by G>A changes and can be converted to inosine (which mimics guanosine during translation) by an RNA editing therapeutic strategy. Here we propose an approach aimed at correcting the mutant copy using long RNA oligonucleotides able to recruit endogenous adenosine deaminases to the target site, to convert the mutant allele (A) to wild type (G) and potentially fully restore the normal collagen VI levels.
Period of Support From:
September 2020 To: August 2022
150,000$ (in 2 years, 75,000 each year 20-21)
Contributions made by Noelia Foundation
February, 2021: $75.000 Proof of transfer
Place of development
NINDS National Institute of Neurological Disease and Stroke, Bethesda, Maryland USA
Researchers involved (NIH/NINDS):
- Principal Investigator , Bönnemann, Carsten G., MD
- Brull Cañagueral, Astrid, Postdoctoral Fellow (100%)
- Bolduc, Veronique, Research Fellow (10%)