Saturday, November 20, 2004

Alternative Splicing Microarrays Incoming

Agilent and ExonHit Therapeutics announced a research partnership aiming to allow detection of gene splicing variants. Alternative splicing allow for different proteins to be produced from an unique gene. Its an additional layer of biological complexity that we're only beginning to understand.

Sadly, current microarrays can't differentiate between spliced transcripts; they usually only differ by the presence/absence of a coding segment (exon), the rest is 100% identical. Combining Agilent microarray platform (60-mers cDNA-based / one probe per gene, sadly) with ExonHit DATAS technology promise to eliminate this shortcoming.

Excerpt from the press release : "Agilent Technologies Inc. (NYSE: A) and ExonHit Therapeutics, a private drug discovery company, today announced a research collaboration to combine Agilent's microarray platform and ExonHit's alternative RNA splicing technologies and expertise. This collaboration explores the development of a microarray-based solution that will enable scientists to properly monitor the expression of splice variants.

Splice variants are variable sequences of RNA produced from the same gene in DNA, resulting in the creation of different proteins potentially affecting cellular regulation. Scientists developing therapeutics are increasingly interested in this emerging field as the expression of splice variants can provide novel targets, may indicate disease states, and can be altered by exposure to drugs and toxins.

Agilent and ExonHit are working together to optimize microarray design, reagent protocols and data analysis methods for splice variant studies. As a pioneer in alternative RNA splicing, ExonHit realized that the proper characterization of splice variant expression required dedicated profiling platforms. The company has received notice of the allowance of its patent, which broadly claims nucleic acid arrays that enable the detection of alternative RNA splicing events via either intron or exon and splice junction-specific probes. Agilent is a leader in the gene expression field, providing researchers highly flexible and sensitive printed microarrays.

Initial results from an experimental splicing array of G-protein coupled receptors, designed by ExonHit and produced by Agilent pursuant to the collaboration, were presented at Splicing 2004, an annual symposium on alternative RNA splicing, by Richard Einstein, vice president of R&D North America at ExonHit. The array detected multiple isoforms of several genes, and showed good reproducibility and specificity. The companies are expected to work with early test sites to generate additional experimental results."

Personally, I think that Affymetrix technology is superior to solve the alternative transcript quantification problem; I sure hope that they give it a shot. With more probes (typically 12x2/gene) than Agilent microarrays, even if they're smaller (12-mers vs 60-mers) would allow for a more precise quantification by tiling known exons... I'll wait for the actual product from the Agilent / Exonhit partnership and their implementation to judge tough.

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