siRNA-based inhibition specific for mutant SOD1 with single nucleotide alternation in familial ALS, compared with ribozyme and DNA enzyme
Détails
ID Serval
serval:BIB_3A2F08A95BBF
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Institution
Titre
siRNA-based inhibition specific for mutant SOD1 with single nucleotide alternation in familial ALS, compared with ribozyme and DNA enzyme
Périodique
Biochemical and Biophysical Research Communications
ISSN
0006-291X (Print)
Statut éditorial
Publié
Date de publication
01/2004
Volume
314
Numéro
1
Pages
283-91
Notes
Comparative Study
Evaluation Studies
Journal Article
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, P.H.S. --- Old month value: Jan 30
Evaluation Studies
Journal Article
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, P.H.S. --- Old month value: Jan 30
Résumé
In many of autosomal dominant diseases such as familial amyotrophic lateral sclerosis (ALS) with SOD1 mutation, a missense point mutation may induce the disease by its gain of adverse property. Reduction of such a mutant protein expression is expected to improve the disease phenotype. Duplex of 21-nt RNA, known as siRNA, has recently emerged as a powerful tool to silence gene, but the sequence specificity and efficacies have not been fully studied in comparison with ribozyme and DNA enzyme. We could make the siRNA which recognized even a single nucleotide alternation and selectively suppress G93A SOD1 expression leaving wild-type SOD1 intact. In mammalian cells, the siRNA much more efficiently suppressed the expression of mutant SOD1 than ribozyme or DNA enzyme. Furthermore, these siRNAs could suppress cell death of Neuro2a induced by over-expression of mutant SOD1s with stress of proteasome inhibition. Our results support the feasibility of utilizing siRNA-based gene therapy of familial ALS with mutant SOD1.
Mots-clé
Amyotrophic Lateral Sclerosis/genetics/metabolism/therapy
Animals
Cell Line
DNA, Catalytic/genetics/*metabolism
Feasibility Studies
Gene Expression Regulation, Enzymologic/genetics
Gene Silencing
Gene Therapy/methods
Humans
Kidney/embryology/*metabolism
Mice
*Mutagenesis, Site-Directed
Neuroblastoma/*metabolism
Protein Engineering/methods
RNA, Catalytic/genetics/*metabolism
RNA, Small Interfering/genetics/*metabolism
Superoxide Dismutase/*genetics/*metabolism
Pubmed
Web of science
Création de la notice
29/01/2008 9:44
Dernière modification de la notice
20/08/2019 14:29