Collaborators Develop Special Microarray System

An American electronics manufacturer has teamed up with a French biotechnology company to develop a microarray system for monitoring the expression of RNA splice variants.

The human genome-sequencing project estimated the number of human genes to be between 30,000-40,000, which is much less than the previous estimates based on analysis of expressed sequence tags (ESTs, 100,000-150,000 genes). This increased diversity at the mRNA level can, in part, be accounted for by alternative RNA splicing. Researchers in this area maintain that understanding this diversity will be critical for future drug discovery and diagnostics efforts.

RNA splicing is an essential, precisely regulated post-transcriptional process that occurs prior to mRNA (messenger RNA) translation. A gene is first transcribed into a pre-messenger RNA (pre-mRNA), which is a copy of the genomic DNA containing intronic regions destined to be removed during pre-mRNA processing (RNA splicing), as well as exonic sequences that are retained within the mature mRNA. During RNA splicing, exons can either be retained in the mature message or targeted for removal in different combinations to create a diverse array of mRNAs from a single pre-mRNA, a process referred to as alternative RNA splicing.

Alternative splice events that affect the protein-coding region of the mRNA give rise to proteins that differ in their sequence and therefore in their activities. Alternative splicing within the noncoding regions of the RNA can result in changes in regulatory elements such as translation enhancers or RNA stability domains, which may have a dramatic effect on the level of protein expression.

To develop new technology to monitor expression of splice variants, Agilent Technologies Inc. (Palo Alto, CA, USA), an electronics manufacturer with a proven microarray platform, has collaborated with ExonHit Therapeutics (Paris, France), a private drug discovery company with expertise in alternative RNA splicing technologies.

The two companies are working to optimize microarray design, reagent protocols, and data analysis methods for splice variant studies. Initial results from a prototype splicing array of G-protein coupled receptors designed by ExonHit and produced by Agilent detected multiple isoforms of several genes and showed good reproducibility and specificity.

"Our mutual goal is to better enable alternative RNA splicing analysis using microarray technologies,” said Fran DiNuzzo, vice president and general manager of Agilent's integrated biology solutions business unit. "ExonHit Therapeutics has developed an impressive process for the identification of splicing patterns that point to specific targets for therapeutic intervention. By collaborating, we can define methods that deliver more informative splice-variant expression analysis for drug research and development.”

Bruno Tocque, CEO of ExonHit Therapeutics said, "The effectiveness of Agilent's microarray platform, combined with ExonHit's pioneering alternative RNA splicing technology and strong intellectual property position, will ultimately provide an ideal expression-profiling solution for researchers worldwide.”


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Agilent Technologies Inc.
ExonHit Therapeutics