05-033: SiRNAs with an Enhanced Specificity to the Target

George Mason University researchers have developed an algorithm that enables the rapid design of siRNAs with minimized off-target hybridization.

Small interference (si) RNAs can silence gene expression by interfering with the stability and translation of messenger RNA. Its effectiveness, however, can be compromised because the 21 - 23 nucleotide length of the siRNAs now available may degrade unrelated RNA.
The siRNAs designed by using the GMU algorithm are comprised of shorter, truly unique overlapping sequences of 12-15 nucleotides, resulting in greater targeting specificity.

The GMU oligonucleotides can be used both for therapeutic and experimental siRNA silencing and as gene-specific sets of probes for long oligonucleotide based expression microarrays or for Real-Time PCR. This invention provides methods and systems for identifying unique polynucleotide sequences within a larger polynucleotide sequence.

The methods and systems are useful for designing unique polynucleotides for a variety of purposes such as probes, primers, transcription or translation modulators, siRNA, capture labels, etc. Polynucleotides can be used in silencing or interference RNA technologies, PCR (including quantitative PCR), microarrays, etc.

Market Significance:
iRNA technology will have a significant impact on the development of treatments for a variety of diseases including cancer, infectious diseases, and autoimmune disorders.

The GMU designed siRNA will provide:
- More specific gene targeting, reducing one of the most prevalent problems associated with the use of RNA interference technology.
-Reduction in the number of degraded genes, thus reducing unwanted or unforeseen molecular side effects.
-Increased specificity of probe annealing in micro array and Real-Time PCR type of experiments.
-Easy application to existing technology to provide easier and cleaner readings for diagnostic purposes.
- A cost effective alternative to existing methods of oligonucleotide design.