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270 Peptide Aptamers: New Tools to Capture and Study Protein Interactions in Lieu of Immunological Reagents

Number of anticipated awards: 4
(Fast-Track proposals will be accepted.)
Budget (total costs): Phase I: $150,000;
Phase II: $750,000

The deadline for receipt of all contract proposals submitted in response to this solicitation is:
5:00 p.m. Eastern Standard Time
Monday, November 3, 2008

Summary:
The purpose of this initiative is to provide support for the development of peptide aptamers that can be used instead of antibodies for immunological uses. The Production of polyclonal and monoclonal antibodies is now well established and many of the antibodies are commercially available. Yet, man antibodies remain poorly characterized and suboptimal across multiple applications. In addition, polyclonal antibodies are typically not a renewable resource. Moreover, the specificity of a monoclonal antibody against a target of interest there is not guaranteed, nor is there any certainty as to whether or not a monoclonal will work in the needed assay, or can be used in combination with other antibodies due to an antibody’s large size and subsequent competition for overlapping binding domains. Furthermore, the high costs associated with producing even small quantities of monoclonal antibodies represent a large barrier towards cost-effective reagents and resources for proteomic technology research and clinical adaptation. The goal of this project is to develop reproducible, highly qualified/characterized peptide aptamers as alternative protein capture reagents for the cancer research community. Peptide aptamers are most commonly used as disrupters of protein–protein interactions in vivo, but the flexibility of protein engineering means that peptide aptamers can be turned into tools for virtually any type of biological study. For example, peptide aptamers can provide a basis for the development of novel diagnostic and therapeutic strategies, with implications for a broad variety of different disease entities including cancer. The development of these affinity capture reagents will be done in coordination with NCI’s Clinical Proteomic Technologies for Cancer and be targeted to a list of purified recombinant proteins being constructed and characterized through this initiative.

Project Goals:
NCI is interested in proposals that focus on developing peptide aptamers as alternative affinity capture reagents that can effectively compete against antibody technologies in terms of protein recognition, binding affinity, and detection and can be reproducibly produced in a cost-effective and efficient manner. Furthermore, these capture reagents must pass performance characterization criteria and be made available as a resource to the scientific community.

The peptide aptamers are required to demonstrate equivalent or improved performance to other affinity-based platforms. It is expected that peptide aptamers have dissociation constants that are comparable to or better than antibodies and can be used in the same way as antibodies. Suggested choices of performance applications that could be validated include immunoblot, and immunoprecipitation. In addition, other considerations include the actual binding epitope, and application in multiplex platforms such as microarrays. While it is expected that initial development and quality assurance/quality control costs may be comparable to that of monoclonal antibodies, it is intended that production costs of these renewable reagents will be significantly lower.

Offerors are encouraged to coordinate selection of analytes with the Clinical Proteomics Technologies for Cancer community during Phase I. Targets for Phase II are to be selected in coordination with this community included in the following reference: Malu Polanski and N. Leigh Anderson. (2006) “A List of Candidate Cancer Biomarkers for Targeted Proteomics.” Biomarker Insights 2:1-48.

Phase I Activities and Expected Deliverables

• Demonstrate feasibility of the innovative method for peptide aptamer production
• Work with the clinical proteomics community and private and public sectors to identify appropriate minimum characterization criteria/validation assays
• Generate peptide aptamers to at least 10 protein targets and demonstrate equivalent or improved performance to other affinity-based platforms
• Demonstrate that peptide aptamers have improved cost effectiveness and throughput capabilities in production compared to antibodies
• Present findings to NCI program staff
• Research should be proposed with quantitative feasibility milestones

Phase II Activities and Expected Deliverables

• Implement strategy and project plan for a fully functional peptide aptamer reagent development platform for at least 100 protein targets. The reagents should be able to capture the target of interest from complex biological mixtures such as blood, plasma, or tissue.
• Test performance criteria against other affinity platforms
• Work with the cancer clinical proteomics community to integrate the platform into the technology assessment programs and greater scientific community.
• Research should be proposed with quantitative feasibility milestones.