DNAS Awarded NIH Grant to Study Modified Nucleic Acids

Ann Arbor, Michigan – September 7, 2006DNA Software has been selected for a Grant issued by the National Institute of Health (NIH). The fast track grant, entitled “Database for Modified Nucleotides, Fluorophores and Additives” has been approved for Phase I and Phase II funding. Phase I, scheduled from November 1, 2005 to May 1, 2006, has recently been completed. Phase II is scheduled to start October 1, 2006.

Phase I
In Phase I of this project survey measurements on morpholino modified oligonucleotides and on 5-methylisocytosine and isoguanine match and mismatch duplexes have been performed. These measurements form the basis for the design of some of the experiments for phase II.

Previously determined effects of glycerol on nucleic acid denaturation have been incorporated into Visual OMP™. The last phase I accomplishment was to add previously determined parameters for deoxyinosine substitutions in DNA duplexes to Visual OMP™; these will be available to Visual OMP™ users in the next update.

Phase II
Besides completing the morpholino:RNA match, Morpholino:RNA dangling end, and iC and iG thermodynamic parameter databases in phase II, systematic measurements will be made to also complete the thermodynamic parameter database for PNA. These measurements include PNA:RNA matches, PNA:PNA matches, PNA hairpins, PNA:DNA mismatches and PNA:DNA dangling ends.

The other Phase II goals include completing the thermodynamic parameter database for 18 commonly used labels (fluorophores, quenchers, and biotin), and determining the thermodynamic corrections for duplex stability as a function of concentration for the additives DMSO, Betaine, SYBR-Green, TMAC, and formamide.

Lastly, these newly determined parameters and dependencies will be incorporated into Visual OMP™, and a module to design custom probes with modified nucleotides will be developed.

DNA Software expects Phase II to be completed by October of 2007. Astrid Tuin, DNA Software’s lab director states that “The Phase II experiments, analysis of the data and software development are carefully planned, so we expect phase II of this exciting project to go smoothly. All of the goals should be accomplished on time.”

Background and significance of the project
Well designed morpholino oligonucleotides can be used as an efficient and specific oligonucleotide-based antisense reagent in the field of functional genomics to match biological function(s) with gene sequence.

The pairing capability of iC and iG has been employed for molecular recognition and site-specific incorporation by DNA polymerase. In complex assays where high levels of natural DNA of known or unknown sequences exist, the orthogonal pairing capability of iC-iG allows for specific molecular recognition to take place without interference.

PNA has excellent properties, like chemical and biological stability, enhanced hybridization affinity to DNA and RNA, and incorporation of non-natural nucleobases, that can be used for diagnostics, antigene and antisense therapies, and antiviral and antimicrobial PNA therapies.

By determining the thermodynamic influences of labels (fluorophores, quenchers) and different additives, Visual OMP™ can help improve design of (multiplex) Real Time PCR assays, leading to higher efficacy and specificity.

About DNA Software, Inc.
DNA Software, Inc. combines science and software to enable industrial genomics through advances in technologies based on nucleic acids. The company’s first software platform, OMP™ (Oligonucleotide Modeling Platform™), models in silico the folding and hybridization of single-stranded nucleic acids with great accuracy. The company combines OMP™ with scientific consulting, custom software development, and custom laboratory research to deliver state-of-the-art support for designing and developing of nucleic acid based technologies.