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NOVEL CLEAVABLE NUCLEOTIDES FOR DNA SEQUENCING BY SYNTHESIS

Award Number: R43HG004470
ORGANIZATION: NATIONAL HUMAN GENOME RESEARCH INSTITUTE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 04/09/2008
PERIOD OF PERFORMANCE END DATE: 03/31/2009

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NOVEL CLEAVABLE NUCLEOTIDES FOR DNA SEQUENCING BY SYNTHESIS - DESCRIPTION (provided by applicant): Intelligent Bio-Systems is developing a high-speed, low-cost DNA sequencing-by-synthesis (SBS) system which is based on the use of cleavable fluorescent nucleotides with reversible terminator technology. The cleavable linkers utilized in these nucleotides enable efficient removal of fluorescent signals and the reversible terminator technology enables reliable sequencing of repeats. In order to extend the performance of the sequencing system, we believe it is important to minimize the effect of residual linker on the nucleotide bases left behind after cleavage. These residual linkers may disturb the DNA duplex structure and interfere with a polymerase's ability to incorporate subsequent nucleotides. The goal of this Phase I project is to synthesize and evaluate several novel cleavable nucleotides which generate minimal residues after cleavage. We anticipate that the use of such nucleotides should result in much higher cumulative cycle efficiency in the SBS and enable longer sequencing reads. During Phase I of this project we will synthesize, characterize and extensively evaluate two novel designs of nucleotides which will generate smaller residues after fluorescent signal removal. The performance of novel nucleotides will be compared with the performance of our standard design cleavable nucleotides in solution and on solid surfaces. During Phase II we will synthesize and characterize 4 nucleotides based on the best performing analogs and perform synthesis optimization and scale-up. Phase II will also involve evaluation of all 4 nucleotides in our sequencing instrument. Ultimately, the ability to produce very inexpensive detailed DNA sequence information for complex organisms' genomes will both lead to accelerated discoveries throughout biology and provide the basis for Pharmacogenomics, a new paradigm in therapeutics wherein medicines are prescribed based on individual genotypes rather than just observed symptoms. Public Health Relevance: This Public Health Relevance is not available.


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2008 ( Subtotal = $162,574 )
2008	2008	INTELLIGENT BIO-SYSTEMS INC	25 ROLLING LANE	WESTON	MA	02493	MIDDLESEX	USA	Human Genome Research	000	1	4/7/2008	NEW	$162,574
														Subtotal = $162,574

Grand Total All Awards = $162,574

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NOVEL CLEAVABLE NUCLEOTIDES FOR DNA SEQUENCING BY SYNTHESIS

Award Number: R43HG004470

ORGANIZATION: NATIONAL HUMAN GENOME RESEARCH INSTITUTE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

PERIOD OF PERFORMANCE START DATE: 04/09/2008

PERIOD OF PERFORMANCE END DATE: 03/31/2009

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