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Cotranslational Protein Expression System for High-throughput Screening

Posted Aug 05 2013 8:00pm

Description of Invention:
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.

Applications:
High-throughput screening of chemical libraries in a single assay platform for commercial or research use.

Advantages:
This method will significantly enhance the ability to identify and prioritize active compounds from reporter gene-based assays.

Development Status:
Early-stage

Inventors:
James Inglese (NCATS)
Chih-Chien (Ken) Cheng (NCATS)
Samuel A Hasson (NCATS)


Patent Status:
HHS, Reference No. E-300-2012/0
PCT, Application No. PCT/US2013/032184 filed 15 Mar 2013


Relevant Publication:
  1. Chan K, Inglese J. [ PMID 23018994 ]


Collaborative Research 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 .


For Licensing Information Please Contact:
Tara Kirby Ph.D.
NIH Office of Technology Transfer
6011 Executive Blvd. Suite 325,
Rockville, MD 20852
United States
Email: tk200h@nih.gov
Phone: 301-435-4426
Fax: 301-402-0220


Ref No: 2608

Updated: 08/2013

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