Improved Design of Oligonucleotides and Oligo-Probes for Antisense Technology, Gene Expression Profiling, and Molecular Diagnostics
Many techniques of molecular biology require interaction of oligonucleotide probes (oligo-probes) with DNA or RNA targets as a basic step in their procedure. Efficient hybridization of oligo-probes is critical to the implementation of molecular assays for pathogen detection, genetic screening and diagnosis, and pharmacogenetic analysis. Other important applications include microarray technologies for monitoring gene expression and antisense-mediated gene silencing. In all of these cases, efficient interaction between an oligo probe and a target is crucial.
These technologies describe algorithms for predicting oligo-probe hybridization efficiency by combining sequential filtering procedures with experimentally determined thermodynamic cutoff points to predict which specific sequences in a target are most suitable as the basis for probe design. These algorithms have been applied to identify optimum RNA target regions of the HIV-1 genome which could be used for improved HIV detection and quantitation.
The market for DNA/RNA probe technology is large and growing. Two of the main categories are microarrays and antisense technology. Microarray-based profiling of gene expression is an important tool for drug discovery and validation, as well as diagnostics. Antisense technology has the potential to create an entirely new sector of the pharmaceutical industry. Currently, antisense technology is being used in drug discovery programs focused on novel treatments for a wide range of diseases, and as a tool for functional genomics. The algorithms in these inventions could have an significant impact in the optimization and application of both of these technologies, decreasing the costs and increasing efficiency.
Stage of Development
Two formal patent applications have been filed with the U.S. Patent Office. This technology is part of an active and ongoing research program and has been validated in proof-of-concept experiments that include a software prototype. It is available for developmental research support or licensing under either exclusive or non-exclusive terms.
*Matveeva et al. (2003). Thermodynamic criteria for high hit rate antisense oligonucleotide design. Nucleic Acids Res;31(17):4989-94.
*Matveeva et al. (2003). Thermodynamic calculations and statistical correlations for oligo-probes design. Nucleic Acids Res;31(14):4211-7.
*Matveeva et al. (2004). Identification of regions in multiple sequence alignments thermodynamically suitable for targeting by consensus oligonucleotides: application to HIV genome. BMC Bioinformatics;5:44.
Olga Matveeva, Raymond Gesteland, Svetlana Shabalina, John Atkins
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