Gene Therapy for ALS with mutant SOD1 by ribozyme and catalytic DNA.

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Recently, short interfering RNA (siRNA) has been found to cleave efficiently RNA, so that we compared its efficiency for the supprresion of expression of target gene with ribozyme and catalytic DNA. In culture cells the siRNA designed for wild-type SOD1 was much more efficient to suppress the expression of SOD1 than ribozyme and catalytic DNA. When single nucleotide alternation was positioned at 9-13th nucleotide from 5' side in the sense sequence of siRNA, it can recognize a single nucleotide alternation. Using this principle, we succeeded in making the siRNA which specifically suppress the expression of mutant G93A SOD1 without influencing that of the wild-type SOD1.For the efficient delivery of siRNA to neurons, development of the virus vectors might be necessary. First, excellent siRNA-expressing DNA vector was constructed when the U6 promotor and the stem-loop sequence of siRNA were used. Second, with this expression cassette, we successfully made siRNA-expressing adnovirus and adno-associate virus vectors. Therefore, we finish the first step of the gene therapy for ALS with mutant SOD1.