DNA Software Awarded NIH Grant to Study Modified Nucleic Acids
Ann Arbor, Michigan - September 7,
2006 – DNA 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. For more information
on DNA Software, Inc., visit our web site at http://www.dnasoftware.com.
CONTACT:
DNA Software, Inc.
204 East Washington Street
Ann Arbor, MI 48104
Office: +1 (734) 222-9080
Toll-Free: +1 (877) 362-7638
Fax: +1 (734) 222-9087
Email: info@dna-software.com
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