CombiMatrix is able to synthesize large libraries of RNAi compounds in parallel. This allows testing of the biological function of each of these molecules and empirically determine the most effective approach. These "molecular libraries" are synthesized using our parallel synthesis technologies on a semiconductor biochip. The design of the RNAi molecules is guided by a host of bioinformatic tools developed to significantly reduce the likelihood of unintended side effects and maximize efficacy. Our adaptable chip platform enables us to test the efficacy of large numbers of compounds then redesign and keep evolving the design of our RNAi molecules.

CombiMatrix is working to develop partnerships with organizations with the most promising delivery technologies to bring our siRNA compounds to clinical trials.

CombiMatrix has integrated its semiconductor-based parallel oligonucleotide synthesis platform with streamlined screening activities for the discovery and development of novel RNAi-based therapeutics. The CombiMatrix Drug Discovery Program integrates the following functions:

• Gene target or pathogen identification
• Bioinformatics construction of sequence libraries
• Chip-based parallel synthesis of siRNA compounds
• Parallel in-vitro siRNA library screening
• Optimization and validation of lead siRNA compounds using CombiMatrix's customizable gene expression microarrays
• Advancement of lead compounds into clinical development with pharmaceutical partners

Different siRNA compounds are produced in parallel for each target gene using CombiMatrix's microarray-based in situ synthesis platform. The parallel synthesis approach permits cost-effective production and screening of a large number of siRNA compounds at one time. Small and large pools of different siRNA compounds are generated that specifically target a single gene or entire pathogen genomes.

Suitable compounds for gene silencing are identified using in-vitro screening assays. In addition, CombiMatrix's customizable gene expression microarrays are used to determine the specificity of gene silencing within target systems. For example, an ideal siRNA compound has complete specifity for the target it is intended to inhibit and does not affect any other gene in the system. CombiMatrix's customizable gene expression microarrays are used to determine the specificity of each lead RNAi candidate using a comprehensive approach.