Agency: Department of Health and Human Services | Branch: | Program: SBIR | Phase: Phase I | Award Amount: 156.81K | Year: 2014
DESCRIPTION (provided by applicant): Cancers selected for the NIH's The Cancer Genome Atlas (TCGA) project have been chosen because of their poor prognosis and overall public health impact. Select tissue samples have been profiled for gene and miRNA expression, promoter methylation, DNA sequence and mutation analysis, as well as copy number variation (CNV), with total expenditures of 275 Million13. The copy number variation (CNV) information, derived from the raw array-based comparative genomic hybridization (aCGH) and SNP-array data, has been successfully utilized in specific application areas, such as identification of significant recurrent aberrations in each tumor type from population-wide, tumor- specific analysis. However, the full potential of this data has not yet been exploited. The two major obstacles have been the method used to perform the initial data processing which have somewhat limited its utility, and the lack of a comprehensive integrated data access and analytical platform for copy n
Agency: Department of Health and Human Services | Branch: | Program: SBIR | Phase: Phase I | Award Amount: 214.71K | Year: 2010
DESCRIPTION (provided by applicant): There is a growing demand for custom synthesis of short genes libraries coding for active peptides or regulatory RNAs. DNA microarrays can be manufactured by synthesizing oligonucleotides on solid substrate in a massively-parallel manner using a high-yield low cost chemistry. Oligonucleotides can be cleaved off the microarray surface and recovered as a pool. Our hypothesis is that we can use this technology to create custom libraries of long DNA oligonucleotides at a much reduced cost and increased complexity compared to current technologies. Our long term objectives are to implement a commercial service of affordable custom synthesis of long oligonucleotide libraries. These libraries are used as a research tools in many applications such as studies on gene silencing, protein-DNA interaction, epitope mapping or even antimicrobial peptides. There are no limits for applications than the imagination of scientists. The heath relatedness of the project resides in the facts that these applications lead to the discovery of new cellular mechanisms, diagnosis tools, drugs or even vaccines. The scope of the proposed project is 1) to demonstrate the feasibility of using an emulsion-based PCR to amplify oligonucleotide libraries; 2) to investigate the possibility to synthesize libraries of oligonucleotide up to 150 mer in length and 3) to determine the synthesis error rate and type of sequence mutations present in these libraries. We will in particular test the effect of droplet size and number of templates per droplet on the PCR amplification of oligonucleotide template in an emulsion. We wil characterize the complexity of an amplified library by deep-sequencing a PCR product. The large amount of sequence information obtained will also permit an in depth characterization the type of errors occuring during massively-parallel long oligonucleotide synthesis. PUBLIC HEALTH RELEVANCE: The unprecedented availability of affordable custom libraries of long oligonucleotides will enable new experimentations in fields such as gene silencing, protein-DNA interaction, epitope mapping or even antimicrobial peptides. This technology will undoubtedly bolster the discovery of new cellular mechanisms, diagnosis tools, drugs or even vaccines, ultimately benefiting the society.
Agency: Department of Health and Human Services | Branch: | Program: SBIR | Phase: Phase I | Award Amount: 219.26K | Year: 2010
DESCRIPTION (provided by applicant): Peptides play a significant role in the defense mechanisms of the body and binding of cells, bacteria and viruses to surfaces. Combinatorial peptide chemistry has emerged as a powerful tool for mapping receptor-ligand interactions in drug discovery applications as well as epitope mapping. There is a huge, but largely unrealized, potential for peptide microarray applications in drug discovery, study of cellular pathways and treatment of tumors. There are two reasons why the peptide micro arrays have not yet reached their potential: i) the enormous diversity possible with peptide microarrays as well as ii) the high cost of peptide microarrays in comparison to DNA microarrays. In this proposal our goals are to: 1) Develop a highly flexible and fast in situ custom peptide synthesis technology which can lower the cost of peptide microarrays by at least an order of magnitude and reduce the synthesis time to less than 24 hours for peptides containing up to 15 amino acids; 2) Increase the density of peptides on a microarray by an order of magnitude to gt10,000/array; 3) Use fluorescent probes as well as high resolution mass spectroscopy to determine sequence purity and stepwise yields for addition of each of the 20 naturally occurring amino acids. We have developed a revolutionary light gated oligonucleotide microarray synthesis technology which uses off the shelf reagents and a modified projector to carry out custom microarray synthesis on open or curved surfaces with probe densities of up to 500K/glass slide for about one tenth the cost of most commercial microarrays of similar density. In this project we will modify the chemistry and instrumentation used for oligonucelotide microarray synthesis to develop a system for combinatorial peptide synthesis on open/closed slide surfaces or membranes.
Agency: Department of Health and Human Services | Branch: | Program: SBIR | Phase: Phase I | Award Amount: 307.41K | Year: 2012
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 longoligonucleotide 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 bearingsequence-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 surveyedfrom 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.
Biodiscovery, Inc. | Date: 2016-02-15
Biodiscovery, Inc. | Date: 2014-11-03
Biodiscovery, Inc. | Date: 2013-01-15
SOFTWARE AND COMPUTER SYSTEMS FOR BIOTECHNOLOGY RESEARCH APPLICATIONS, NAMELY, SOFTWARE AND COMPUTER SYSTEMS COMPRISING A CPU, DISPLAY DEVICE, AND KEYBOARD FOR USE IN BIOINFORMATICS AND GENE EXPRESSION MICROARRAY IMAGE ANALYSIS.
Biodiscovery, Inc. | Date: 2012-08-24
Biodiscovery, Inc. | Date: 2012-11-21
Agency: Department of Defense | Branch: Defense Advanced Research Projects Agency | Program: SBIR | Phase: Phase I | Award Amount: 149.66K | Year: 2015
Cell-free expression systems are becoming robust platforms to reduce system complexity, to use toxic and non-naturally occurring compounds or to produce metabolic intermediates, proteins and molecules that are otherwise toxic to cells. Unfortunately, current cell-free expression platforms are often inconsistent, low scale, not flexible, poorly characterized and limited to relatively simple biological processes, which has prevented their widespread adoption. There is a critical need for a consistent, reliable and commercially available cell-free transcription/translation (TXTL) system that integrates the last progresses made in this area. Here we propose to develop a commercial TXTL offer based on a powerful E. coli based cell-free platform that recently emerged as a promising technology for in vitro prototyping and expression of complex molecular programs. This system is the first to use the endogenous transcription machinery in addition to the T7-based systems, expanding the repertoire of transcription to hundreds of parts. As a consequence, it has a unique versatility for prototyping biomolecular networks. This platform is also highly tunable, both at the transcription and translation level, enabling fine gene circuitry regulations. The commercialization of this technology will enable widespread use of cell-free platforms for rapid prototyping and biomanufacturing.