SBIR-STTR Award

Members of the United States Armed Forces are faced with a wide variety of existing, genetically engineered and emerging biological threats. There is a critical need for a fieldable system for rapid microbial assessment of environmental and clinical samples. A system is needed to identify signatures in a complex background with extremely low false positives. Genetic biomarkers target molecular elements that are key to determining course of action, such as virulence mechanisms and antibiotic resistance. GenArraytion proposes to develop a signature sequence microarray for various Staphylococcus aureus strains, including those that are antibiotic resistant. Our hybridization based microsequencing approach provides rapid, accurate and sensitive identification and characterization for early detection of outbreaks. The massively parallel genetic analysis can identify novel, previously uncharacterized organisms and can be automated for field and hospital use. GenArraytion’s Sniper Sequencing identifies hundreds to thousands of unique and functional biomarkers per genome, including markers that are specific at the genus, species and strain levels. Functional elements of pathogens, such as virulence factors, infectious pathway elements and antibiotic resistance, are combined with organism-specific signatures to provide a detailed fingerprint that can discriminate between closely related microbial strains, characterize previously unknown strains, and provide indications of genetic manipulation.

Keywords:
Occult Pathogen, Biomarker, Sequencing, Pathogen, Antibiotic Resistance, Virulence Factor, Microarray, Whole Genome Amplification

The objective of this proposed SBIR Phase II effort is to develop diagnostic assays based on a set of genetic signatures that provide actionable, sub-species level discrimination, including antibiotic resistance profiles, for high priority pathogens, including occult and emerging varieties. The combination of a universal amplification and labeling system with the beaded array will provide a revolutionary improvement in medical molecular diagnostics with unprecedented fidelity and adaptability to identify occult and emerging disease agents. These assays will have broad applicability in military and commercial settings, as they will enable rapid action needed to reduce mortality, morbidity and treatment costs. We will screen the genetic profiles of up to 100 clinical isolates of Staphylococcus aureus with known antibiotic resistance profiles using a 4,000+ feature planar microarray in order to develop a signature set of high value markers for rapid, treatment-based assays to identify MSSA and MRSA. In parallel, we will develop a multi-signature per organism multiplexed assay for the three major biothreat organisms, Bacillus anthracis Ames, Yersinia pestis, and Franciscella tularensis. These assays will be developed using the Luminex system, which provides the basis for flexible, rapid, low cost diagnostic assays. A respiratory viral panel has been FDA-approved on this platform.

Keywords:
Molecular, Diagnostic, Multiplex, Array, Bead, Assay, Luminex, Staphylococcus, Aureus, Mrsa, Mssa