Overview

To understand what makes a cell function normally and what may go awry in disease, we need better tools and resources, such as renewable protein capture reagents and probes, to study how proteins work in isolation and how they interact with other proteins, carbohydrates, or DNA regions within a cell. Ideally, this resource would allow us to identify and isolate all proteins within cells, in their various forms – the so called “proteome” – to ensure broad application in research and clinical studies aimed at understanding, preventing, detecting and treating disease. Existing protein capture reagents, such monoclonal antibodies, have been developed for a number of protein targets, although these represent only a subset of all proteins comprising the human proteome. In addition, many monoclonal antibodies lack the desired level of specificity and do not reliably target only the protein of interest. This is particularly problematic given the multiple forms of any one protein and the broad range of protein types in the body.

A renewable resource of protein capture reagents – specifically designed to meet research and clinical demands ranging from protein isolation and high-throughput assays to diagnostics and biomarker development – is needed to advance the field of proteomics and fuel biomedical research. To have the maximum benefit, such reagents would need to be high quality, affordable, reliable monoclonal antibodies and other reagents that can collectively target the range of possible proteins within cells and tissues. But what do these reagents look like and how can they be developed, optimized and scaled for use in large-scale proteomics research and clinical applications? The Common Fund Protein Capture Reagents program seeks to address these questions and establish a “protein capture” resource of reagents for the biomedical community.

The program is being implemented in phases, with three Funding Opportunity Announcements (FOAs):

• FOA 1: Antigen Production (RFA-RM-10-007) — To produce human transcription factor antigens for making monoclonal antibodies or other affinity capture reagents; this effort is already underway.
  
  
• FOA 2: Anti-Transcription Factor Antibodies Production (RFA-RM-10-017) — To optimize and scale anti-transcription factor capture reagent production to develop a community antibody resource.
  
  
• FOA 3: New Reagent Technology Development and Piloting (RFA-RM-10-018) — To develop improvements in the reagent production pipeline with regard to quality, utility, cost, and production scalability.
  
  

The Protein Capture Reagents Program is organized as a pilot program using transcription factors as a test case to examine the feasibility and value of generating a community resource of low cost, renewable affinity reagents for all human proteins. The reagents must be specifically designed for high quality and broad experimental utility in order to meet the growing demands of biomedical researchers. Based on what is learned from these funding initiatives, the program may expand to a larger production effort to provide a broad community resource of human protein capture reagents.

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