Protease chain reactions for molecular analysis of cancer markers

Award Information
Agency: Department of Health and Human Services
Branch: N/A
Contract: 2R44CA163403-03
Agency Tracking Number: R44CA163403
Amount: $1,808,929.00
Phase: Phase II
Program: SBIR
Solicitation Topic Code: NCI
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): 2018-06-30
Small Business Information
11305 DUNLEITH PL, NORTH POTOMAC, MD, -
DUNS: 193771347
HUBZone Owned: N
Woman Owned: Y
Socially and Economically Disadvantaged: N
Principal Investigator
 BIAO RUAN
 (301) 610-9687
 bruan@potomac-affinity-proteins.com
Business Contact
 BONNIE BRYAN
Phone: (301) 610-9687
Email: bonnie@potomac-affinity-proteins.co
Research Institution
 Stub
Abstract
DESCRIPTION (provided by applicant): Our objective is to develop a Protease Chain Reaction technology (ProCR) that will enable ultra- sensitive and highly-quantitative detection of cancer markers. The basic element of a protease chain reaction is a protease-inhibitor complex. The protease is inactive when bound to the inhibitor but, once freed, is capable of cleaving the inhibitor and releasing additional free protease. A trace of free protease initiates the chain reaction and eventually causes the releaseof all protease from the inhibitory complex. The lag time preceding the full release of protease is determined by the initial concentration of free protease. The Phase I project developed a first-generation of self-amplifying complexes that form the core of the ProCR detection technology. All Phase I milestones were significantly exceeded. In Phase II we will develop powerful molecular sensors based on self- amplifying complexes. A sensor consists of three elements: 1) a sensing element that responds to thepresence of an analyte; 2) the processing/computational element that amplifies and quantifies the signal from the detection element; and 3) the transducer element that produces an optical signal. Through this combination, extremely sophisticated enzymaticsensors will be built to detect cancer markers. Accordingly the three experimental Aims are to: 1) Engineer sensing elements; 2) Engineer enhanced processing/computational elements; and 3) Engineer signaling components. Fundamentally, a protein chain reaction is a powerful analogue computer with two key characteristics that greatly facilitate the detection of target molecules. 1) It can convert th concentration of a specific target molecule into a time signature. 2) It can create enormous signal amplification, analogous to the amplification of DNA by a polymerase chain reaction (PCR). Thus detection is enabled because the final observable signal produced by a target molecule can be very large and the time lag until onset of the signal is precisely correlated with the concentration of target molecule. The long term goal is to develop protease-inhibitor complexes as enzymatic nano-processors which can be combined to detect multiple signals and to control output with multiple logic gates. PUBLIC HEALTH RELEVANCE PUBLIC HEALTH RELEVANCE: The development of polymerase chain reaction (PCR) technology demonstrated the extraordinary power of harnessing an enzyme to perform novel, programmable reactions. Our objective is here to develop an analogous protease chain reaction technology (ProCR) which will enable ultra-sensitive molecular detection. The long term goal is to improve cancer detection and prevention by enabling accurate quantitation of multiple, low abundance molecular markers.

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

Agency Micro-sites

SBA logo
Department of Agriculture logo
Department of Commerce logo
Department of Defense logo
Department of Education logo
Department of Energy logo
Department of Health and Human Services logo
Department of Homeland Security logo
Department of Transportation logo
Environmental Protection Agency logo
National Aeronautics and Space Administration logo
National Science Foundation logo
US Flag An Official Website of the United States Government