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Drug Design Reviews - Online (Discontinued)


ISSN (Print): 1567-2697
ISSN (Online): 1567-2697

Novel RNAi Therapy - Intron-Derived MicroRNA Drugs

Author(s): Shi-Lung Lin and Shao-Yao Ying

Volume 1, Issue 3, 2004

Page: [247 - 255] Pages: 9

DOI: 10.2174/1567269043390898

Price: $65


MicroRNAs (miRNAs) are phylogenetically widespread small RNAs in animals and plants; the origin and function of these molecules in drug design is unknown. Our recent findings of small regulatory RNAs in noncoding regions of the human genome indicate a new strategy for modern drug designs. A novel gene modulation system was found within mammalian introns, regulating intracellular gene transcripts homologous to certain 5- proximal regions of a native intron. These regions are normally located between the 5-splice site and the next branch-point domain. Using Pol-II-directed expression and splicing excision of an artificial intron with various 5- proximal synthetic inserts, we have successfully identified the generation of intron-derived microRNA-like molecules (Id-miRNA) from these regions as a tool for analysis of gene function and development of gene-specific therapeutics. The Id-miRNAs in hairpin conformations deliver maximal RNAi-related gene silencing effects on target genes in several mammalian cells. Based on the diversity of known miRNA structures and the complexity of genomic non-coding regions, the Id-miRNA generation mechanism may lead to one of the major gene modulation systems for developmental regulation, intracellular immunity, heterochromatin inactivation and genomic evolution in eukaryotes.

Keywords: pol-ii-directed rna interference (rnai), micrornas (mirna), splicing-competent intron (sprnai), intronderived mirna (id-mirna)

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