SBIR-STTR Award

The long-term objective of this application is to develop novel products for routine point-of-care (POC) genetic testing, ranging from early cancer detection to pathogen identification by using an innovative biotechnology called, Isothermal Chain Reaction (ICR). ICR is a disruptive and enabling technology platform that will offer a new class of reagents relevant to biomedical research and medical healthcare. ICR does not require any enzymes, primers, nucleotides, master mixes, extension reactions, cDNA intermediates, or thermocycling. These benefits overcome constraints of PCR-based technologies by being resistant to enzyme inhibitors found in laboratory samples and clinical specimens, having higher specificity for rare mutations, and lowering reagent costs. ICR is anticipated to enable selective, rapid, and affordable biomarker detection without having to invest in costly instruments and labor-intensive sample preparation procedures. The envisioned products will be assays, panels, and kits for the early detection of genetic and infectious diseases in non-laboratory settings. Specific Aims: 1. Development of ICR probes to ovarian cancer SNP mutations: We will design and develop ICR assays to rapidly and isothermally detect SNPs that are associated with ovarian cancer mutations. ICR assays that can specifically identify a rare one-in-a-million SNP mutation from a mixed population of templates in less than 10 minutes under isothermal conditions, without enzymes, primers, nucleotides, or master mixes will be selected for use in Specific Aim 2. 2. Identification of somatic SNP mutations in ovarian cancer tumors: We will use selected ICR assays from Specific Aim 1 to identify 46 SNP mutations in DNA isolated from retrospective specimens of ovarian cancer patients. We will determine the percentage of ovarian cancers that are detectable by ICR using our biomarker assays. ICR results will be benchmarked and compared to next-generation sequencing to demonstrate the feasibility of using ICR for routine screening and early detection of cancer SNP biomarkers. Impact: Accomplishing the Specific Aims could significantly impact early detection of ovarian cancer when therapeutic interventions are much more effective, and enable routine clinical testing and screening of the disease to improve clinical triage decisions, routine monitoring, and treatment outcomes.

Public Health Relevance Statement:


Public Health Relevance:
The relevance of this project is to demonstrate the feasibility of early identification of somatic SNP mutations associated with ovarian cancers using a novel isothermal nucleic acid amplification technology. The methods, assays, panels, and reagents used in this project relate to enabling routine early ovarian cancer screening and risk-stratification in point-of-care settings in a rapid, selective, cost-effective, and easy-to-use manner under isothermal conditions.

NIH Spending Category:
Bioengineering; Biotechnology; Cancer; Cancer Genomics; Genetic Testing; Genetics; Human Genome; Ovarian Cancer; Prevention; Rare Diseases

Project Terms:
Address; Asses; base; Bedside Testings; Benchmarking; Biological Assay; Biological Markers; Biomedical Research; Biotechnology; BRCA1 gene; BRCA2 gene; Cancer Detection; Cancer Patient; Caring; Chemistry; Clinic; Clinical; Communicable Diseases; Complementary DNA; cost; cost effective; Data; design; Detection; Development; Diagnostic; Disease; DNA; Early Diagnosis; Early identification; Ensure; Enzyme Inhibitor Drugs; Enzyme Inhibitors; Enzymes; experience; FAT3 gene; Fluorescence; General Population; Genes; genetic panel test; Genetic Screening; Genetic screening method; Genomic DNA; Healthcare; Hereditary Disease; improved; innovation; instrument; Laboratories; Lead; Legal patent; Liquid substance; Malignant neoplasm of ovary; Marketing; Medical; Methods; Monitor; mutant; Mutate; Mutation; Mutation Detection; next generation; next generation sequencing; novel; Nucleic Acid Amplification Tests; Nucleic Acids; Nucleotides; Oligonucleotides; Pap smear; pathogen; Patient Care; Patients; Performance; Phase; Physicians' Offices; point of care; Population; Preparation; Probability; Procedures; public health relevance; Reaction; Reagent; Reporting; Reproducibility; Research; research clinical testing; Resistance; Resolution; Risk; Sample Size; Sampling; screening; Screening for cancer; Screening for Ovarian Cancer; Sensitivity and Specificity; Serous; Somatic Mutation; Specificity; Specimen; Speed; Staging; Statistical Data Interpretation; Stratification; System; Tail; Technology; technology development; Testing; The Cancer Genome Atlas; Therapeutic Intervention; Tissues; TP53 gene; Treatment outcome; Triage; tumor; Universities; Visit