Objectives: The long-term objective of this application is to develop novel products for routine point-of-care (POC) genetic testing, ranging from pathogen identification to early cancer detection 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 infectious and genetic diseases in non-laboratory settings.
Specific Aims : 1. Development of ICR probes to sepsis target sequences: We will design and develop ICR assays to rapidly and isothermally detect synthetic target sequences associated with sepsis in a mixed population of templates in less than 10 minutes under isothermal conditions, without enzymes, primers, nucleotides, or master mixes. 2. Identification of known sepsis pathogens in blood samples: We will use ICR assays from Specific Aim 1 to identify known sepsis pathogens from retrospective blood samples. ICR results will be benchmarked to blood cultures to demonstrate the feasibility of using ICR for rapid early detection of sepsis biomarkers. 3. Identification of unknown sepsis pathogens in blood samples: We will use ICR assays from Specific Aim 1 to identify unknown sepsis pathogens from retrospective blood samples. ICR results will be benchmarked to blood cultures to demonstrate the feasibility that ICR has enhanced selectivity to detect pathogens missed by blood culture methods, and ICR is more amenable to point-of-care sepsis testing. Impact: Accomplishing the Specific Aims could significantly impact rapid and early detection of sepsis pathogens 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

The relevance of this project is to demonstrate the feasibility of rapid and early identification of sepsis pathogens using a novel isothermal nucleic acid amplification technology. The methods, assays, panels, and reagents used in this project relate to enabling routine early sepsis screening and stratification in point-of- care settings in a rapid, selective, cost-effective, and easy-to-use manner under isothermal conditions.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Small Business Innovation Research Grants (SBIR) - Phase I (R43)
Project #
1R43AI126956-01
Application #
9200259
Study Section
Special Emphasis Panel (ZRG1-IDM-V (12)B)
Program Officer
Ritchie, Alec
Project Start
2016-07-01
Project End
2017-06-30
Budget Start
2016-07-01
Budget End
2017-06-30
Support Year
1
Fiscal Year
2016
Total Cost
$300,000
Indirect Cost
Name
Genendeavor, LLC
Department
Type
DUNS #
961957243
City
Fremont
State
CA
Country
United States
Zip Code
94539