Alternative RNA splicing and drug target identification.
Incorporating alternative splicing content into discovery stage DNA microarray expression profiling studies fundamentally increases the relevance of the information obtained. This is because alternative splicing content addresses different parameters to those of conventional microarray content, in that it detects changes that impact the structure and function of gene products, and not simply the quantity of transcription of a given gene. Furthermore, alternative splicing has evolved not as a random process, but as a regulator of protein-protein interactions by preferentially targeting interaction domains for removal, insertion or replacement. In addition, a considerable body of literature is now available linking alternative splicing to the inheritance and pathology of diseases. Alternative splicing affects nearly every gene, with an average of three expressed protein products per gene in humans. ExonHit Therapeutics SA has recently produced the first commercial line of nucleic acid microarrays with splice event resolution that allow detection of not only the reference form of the gene, but also of all the known alternative splice forms. These microarrays enable profiling of the molecular events that are missed with conventional microarrays, and thus permit the key issues of tissue distribution and functional and pharmacological effects of alternative splicing to be addressed earlier in discovery.
Mangasarian
Aram
A
ExonHit Therapeutics SA, 26 rue Brunel, Paris 75017, France. aram.mangasarian@exonhit.com
D017398:Alternative Splicing; D000818:Animals; D017209:Apoptosis; D015195:Drug Design; D006801:Humans; D020411:Oligonucleotide Array Sequence Analysis