ゲノム創薬とDDS

ポストゲノム時代のジーンディスカバリー

抄録

Today, technologies and methods for the rapid identification of functional genes are required with the development of genome informatics. The hammerhead ribozyme, one of the RNA enzymes, is useful for identification of genes by phenotypic changes of cells because of its ability to knock down intracellular expression of target genes by cleaving mRNA specifically. Since the ribozyme has the sequence that is complementary to that of mRNA as the ribozyme target, we can identify a target gene from sequence of a ribozyme by homology search with databases of DNA sequence. Moreover, we improved the efficiency of ribozymes by a combination of the cleavage activity of a ribozyme and the unwinding activity of an endogenous RNA helicase(s) as a hybrid ribozyme. By creating a library of the hybrid ribozyme with randomized substrate-binding arms that cleave multiple mRNAs as knock down library, we can correlate ribozymes and genes with a specific phenotype using the library. Therefore, the system with the ribozyme library should be a powerful tool for identification of functional genes in the post-genome era.