siRNA-based inhibition specific for mutant SOD1 with single nucleotide alternation in familial ALS, compared with ribozyme and DNA enzyme
| Autor: | Ryosuke Takahashi, Taro Hino, Makoto Urushitani, Ryusuke Matsumura, Hidehiro Mizusawa, Kazunari Taira, Rammohan V. Rao, Takanori Yokota, Makoto Miyagishi, Tasinato Andrea, Dale E. Bredesen |
|---|---|
| Rok vydání: | 2004 |
| Předmět: |
Small interfering RNA
animal diseases Mutant Biophysics Kidney Protein Engineering Biochemistry Gene Expression Regulation Enzymologic Cell Line Mice Neuroblastoma Superoxide Dismutase-1 Mutant protein Animals Humans Missense mutation RNA Catalytic Gene Silencing RNA Small Interfering Molecular Biology Gene biology Superoxide Dismutase Point mutation Amyotrophic Lateral Sclerosis Ribozyme nutritional and metabolic diseases RNA DNA Catalytic Genetic Therapy Cell Biology Molecular biology nervous system diseases Mutagenesis Site-Directed biology.protein Feasibility Studies |
| Zdroj: | Biochemical and Biophysical Research Communications. 314:283-291 |
| ISSN: | 0006-291X |
| DOI: | 10.1016/j.bbrc.2003.12.098 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Full Text from ScienceDirect