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Accession number;06A0292922
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| Title;Treatment of Spinocerebellar Degeneration by RNA Interference. |
| Author;
MIZUSAWA HIDEHIRO
(Tokyo Med. and Dent. Univ.)
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Journal Title;Neurological Therapeutics
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Journal Code:X0110A
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ISSN:0916-8443
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VOL.23;NO.1;PAGE.17-24(2006)
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| Figure&Table&Reference;FIG.5, TBL.1, REF.18 |
| Pub. Country;Japan |
| Language;Japanese |
| Abstract;RNA interference (RNAi) is a process whereby small noncoding RNAs silence specific genes. It is important to realize that dsRNAs shorter than 30 base pairs (small interfering RNA: siRNA) could be used to trigger an RNAi response in mammals. Using the RNAi machinery, it would be possible to suppress the expression of genes which cause many intractable neurological diseases including spinocerebellar degeneration (SCD). About 35% of all ACD patients in Japan suffer from hereditary forms most of which are autosomal dominant. Unfortunately, the most common mutation is CAG repeat expansion which appears impossible to be distinguished by siRNA. First, we developed an siRNA specific for G/C polymorphism following CAG repeat in MJD1 gene and fortunately it turned out to work very well specific for the difference between the repeat lengths 22 and 79. However, there is few such polymorphism in spinocerebellar ataxia type 6 (SCA6) although the GGCAG insertion leading to translation of the protein with polyglutamine may be a candidate and we successfully developed siRNA specific for the mRNA with GGCAG insertion. Then we developed a new technique to suppress only the mutant protein by rescuing the normal protein with different base sequences after suppression of the both normal and mutant proteins. The next problem is the delivery of siRNAs to target tissues particularly brain parenchyma which has blood brain barrier. There are also many questions regarding specificity, efficacy, and safety of siRNA therapy in vivo. (author abst.) |
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