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lüll RNA interference: a potential therapeutic tool for silencing splice isoforms linked to human diseases Gaur RKBiotechniques 2006[Apr]; Suppl (ä): 15-22Alternative splicing of precursor messenger RNAs (pre-mRNAs) is one of the most important sources of protein diversity in vertebrates. An estimated 35%-70% of human genes generate transcripts that are alternatively spliced, and defects in this process are linked to numerous human genetic diseases and various forms of cancer. The discovery that 21-23 nucleotide RNA duplexes, known as small interfering RNAs (siRNAs), can knockdown the homologous mRNAs in mammalian cells has revolutionized many aspects of drug discovery including down-regulation of disease-associated splicing isoforms. In addition, RNA interference (RNAi)-mediated silencing of splicing regulators has the potential to define the complex network of alternative splicing regulation and to analyze gene function. In this review, I first provide a brief introduction to mRNA splicing and its relationship to human diseases. This is followed by a brief overview of RNAi. Finally I discuss the therapeutic potential of RNAi in targeting disease-linked splicing isoforms.|*RNA Interference[MESH]|Animals[MESH]|DNA, Recombinant/*genetics[MESH]|Gene Targeting/*methods/trends[MESH]|Genetic Engineering/*methods/trends[MESH]|Genetic Therapy/*methods/trends[MESH]|Protein Isoforms/genetics[MESH]|RNA, Small Interfering/*genetics[MESH] |