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Sorted libraries of error-free long oligonucleotides

Award Information
Agency: Department of Health and Human Services
Branch: National Institutes of Health
Contract: 4R44GM105192-02
Agency Tracking Number: R44GM105192
Amount: $1,105,454.00
Phase: Phase II
Program: SBIR
Solicitation Topic Code: NIGMS
Solicitation Number: PA12-088
Timeline
Solicitation Year: 2013
Award Year: 2013
Award Start Date (Proposal Award Date): N/A
Award End Date (Contract End Date): N/A
Small Business Information
5692 Plymouth rd
ANN ARBOR, MI 48105-
United States
DUNS: 611643813
HUBZone Owned: No
Woman Owned: No
Socially and Economically Disadvantaged: No
Principal Investigator
 JEAN-MARIE ROUILLARD
 (734) 763-4722
 JMROUILL@UMICH.EDU
Business Contact
 JEAN ROUILLARD
Phone: (734) 998-0751
Email: jmr@biodiscovery-llc.com
Research Institution
 Stub
Abstract

DESCRIPTION: Synthetic Biology is full of promises ranging from discovery and production of new drugs, targeted therapies modifying organisms such as yeast or E. coli or creating totally new ones, higher crop yields, CO2 sequestration to bio-energy projects. However, these goals have been difficult to reach primarily due to the difficulty of De Novo gene synthesis and synthesis of new control and regulatory metabolic pathways all the way to synthetic chromosomes from chemically synthesized DNA. Just like any reversible chemical reaction DNA fragment synthesis by sequentially adding the monomers (A,C,G,T) gives less than 100% yield at each step( typical stepwise yields are ~97-99%) as a result the longer the length of DNA to be synthesized the smaller is thefraction of pure product at the end. Elimination of the errors take significant time and money. The goal of this project is to provide error free long oligonucleotides (100 to 300 mers) at a cost lower than the impure DNA fragments of today to unlock thepotential of synthetic biology. We are proposing to make libraries of clonally amplified and sequence verified long oligonucleotides. Our long term objectives are to implement a commercial service of affordable custom synthesis of sequence-verified long oligonucleotide libraries. During Phase I, we will 1) to demonstrate that single oligonucleotide molecules can be clonally amplified and sequence verified, 2) to demonstrate that beads bearing clonal amplifications can be captured on a microarray bearing sequence-specific probes and 3) to demonstrate that sequence verified oligonucleotides enable gene assembly with ten fold reduced error rate. During Phase II, we will 1) to develop a protocol/device to normalize the number of each oligonucleotide surveyed from a library, 2) to establish a standard operating procedure for the production of large libraries of sequence-verified oligonucleotides and 3) to determine the maximum oligonucleotide length that could be offered as a commercial product. PUBLIC HEALTH RELEVANCE The unprecedented availability of affordable custom libraries of sequence verified long oligonucleotides will enable faster, easier and cheaper gene and large DNA fragment assembly with major applications in Synthetic Biology. This technology will undoubtedly bolster the discovery of new cellular mechanisms, molecular therapeutic tools, or even drugs, ultimately benefiting the society.

* Information listed above is at the time of submission. *

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