Cotranslational Protein Expression System for High-throughput Screening


Reporter gene-based assays are used extensively in high-throughput screening (HTS) to identify chemical modulators of cellular pathways for drug discovery and development. However, such screening frequently results in a large number of false “hits” due to interactions of screened compounds with reporter proteins, producing confounding results. Thus, validation of results using these assays often involves significant time and expense.

The inventors have developed an assay system that significantly improves detection of target-relevant active compounds by discriminating between signals arising from the target activity and those caused by reporter bias. This system utilizes simultaneous detection (also known as “coincidence detection”) of non-homologous reporter proteins with dissimilar properties, such as differing catalysis, light emission, or fluorescence characteristics; simultaneous observation of signals from these reporters indicates a high probability that it is a true target response. The reporters are cotranslationally expressed from a single RNA transcript, which ensures stable stoichiometry of the expressed proteins.

Potential Commercial Applications: Competitive Advantages:
  • High-throughput screening of chemical libraries in a single assay platform for commercial or research use.
 
  • This method will significantly enhance the ability to identify and prioritize active compounds from reporter gene-based assays.


Development Stage:
Early-stage

Inventors:

James Inglese (NCATS)  ➽ more inventions...

Chih-Chien (Ken) Cheng (NCATS)  ➽ more inventions...

Samuel Hasson (NCATS)  ➽ more inventions...


Intellectual Property:
US Application No. 14/775,293
PCT Application No. PCT/US2013/032184
US Application No. 15/916,762

Publications:
Chan K, Inglese J. PMID 23018994

Collaboration Opportunity:

The National Center for Advancing Translational Sciences (NCATS) is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate or commercialize Cotranslational Protein Expression System for High-throughput Screening. For collaboration opportunities, please contact NCATS Technology Development Coordinator at NCATSPartnerships@mail.nih.gov.


Licensing Contact:
Ami Gadhia,
Email: ami.gadhia@nih.gov
Phone: 301-217-4679

OTT Reference No: E-300-2012/0
Updated: Nov 18, 2015