Sökning: onr:"swepub:oai:DiVA.org:uu-139357" >
Allele-Selective In...
Allele-Selective Inhibition of Mutant Huntingtin Expression with Antisense Oligonucleotides Targeting the Expanded CAG Repeat
-
Gagnon, Keith T. (författare)
-
Pendergraff, Hannah M. (författare)
-
Deleavey, Glen F. (författare)
-
visa fler...
-
Swayze, Eric E. (författare)
-
Potier, Pierre (författare)
-
Randolph, John (författare)
-
Roesch, Eric B. (författare)
-
- Chattopadhyaya, Jyoti (författare)
- Uppsala universitet,Bioorganisk kemi
-
Damha, Masad J. (författare)
-
Bennett, C. Frank (författare)
-
Montaillier, Christophe (författare)
-
Lemaitre, Marc (författare)
-
Corey, David R. (författare)
-
visa färre...
-
(creator_code:org_t)
- 2010-11-08
- 2010
- Engelska.
-
Ingår i: Biochemistry. - : American Chemical Society (ACS). - 0006-2960 .- 1520-4995. ; 49:47, s. 10166-10178
- Relaterad länk:
-
https://europepmc.or...
-
visa fler...
-
https://urn.kb.se/re...
-
https://doi.org/10.1...
-
visa färre...
Abstract
Ämnesord
Stäng
- Huntington's disease (HD) is a currently incurable neurodegenerative disease caused by the expansion of a CAG trinucleotide repeat within the huntingtin (HTT) gene. Therapeutic approaches include selectively inhibiting the expression of the mutated HTT allele while conserving function of the normal allele. We have evaluated a series of antisense oligonucleotides (ASOs) targeted to the expanded CAG repeat within HTT mRNA for their ability to selectively inhibit expression of mutant HTT protein. Several ASOs incorporating a variety of modifications, including bridged nucleic acids and phosphorothioate internucleotide linkages, exhibited allele-selective silencing in patient-derived fibroblasts. Allele-selective ASOs did not affect the expression of other CAG repeat-containing genes and selectivity was observed in cell lines containing minimal CAG repeat lengths representative of most HD patients. Allele-selective ASOs left HTT mRNA intact and did not support ribonuclease H activity in vitro. We observed cooperative binding of multiple ASO molecules to CAG repeat-containing HTT mRNA transcripts in vitro. These results are consistent with a mechanism involving inhibition at the level of translation. ASOs targeted to the CAG repeat of HTT provide a starting point for the development of oligonucleotide-based therapeutics that can inhibit gene expression with allelic discrimination in patients with HD.
Ämnesord
- NATURVETENSKAP -- Biologi -- Biokemi och molekylärbiologi (hsv//swe)
- NATURAL SCIENCES -- Biological Sciences -- Biochemistry and Molecular Biology (hsv//eng)
Nyckelord
- Biochemistry
- Biokemi
Publikations- och innehållstyp
- ref (ämneskategori)
- art (ämneskategori)
Hitta via bibliotek
Till lärosätets databas
- Av författaren/redakt...
-
Gagnon, Keith T.
-
Pendergraff, Han ...
-
Deleavey, Glen F ...
-
Swayze, Eric E.
-
Potier, Pierre
-
Randolph, John
-
visa fler...
-
Roesch, Eric B.
-
Chattopadhyaya, ...
-
Damha, Masad J.
-
Bennett, C. Fran ...
-
Montaillier, Chr ...
-
Lemaitre, Marc
-
Corey, David R.
-
visa färre...
- Om ämnet
-
- NATURVETENSKAP
-
NATURVETENSKAP
-
och Biologi
-
och Biokemi och mole ...
- Artiklar i publikationen
-
Biochemistry
- Av lärosätet
-
Uppsala universitet