About the Workshop
Purpose: Gather information on the state of the art in technology for production of a comprehensive public resource of affinity reagents for the human proteome.
The NIH Common Fund is exploring the technical and practical ability to produce a comprehensive resource of renewable affinity reagents against the human proteome. As a beginning, in 2010 and 2011, common fund initiatives will solicit production of monoclonal antibodies against human transcription factors. Although monoclonal antibodies are currently a mature methodology, with clear downstream applications already developed, they have drawbacks that may be a practical barrier to creating a more comprehensive set of protein capture reagents. For example, the cost of developing and monoclonal antibodies is high, and is sensitive to the number and type of downstream validations that are applied to ensure wider utility of the reagents.
In addition to monoclonal antibodies, there is a range of alternative technologies such as recombinant antibodies, engineered proteins, and aptamers, which are at various stages of development, and which present some encouraging opportunities to explore towards generating a comprehensive set of protein capture reagents. Given the considerations of cost together with the range of end uses, it may be that a combination of approaches will be needed to generate a comprehensive resource.
Our central question is, what are the most promising approaches for the generation of a complete set of protein affinity capture reagents for wide use by the research community? What are the limitations and advantages of each approach? Which can productively be encouraged to go forward at a “production level” now, and which are further away? What is the timeline for each? What is the best way to stimulate each? What are the advantages or disadvantages of “waiting” until one or more of these are ready for production?
The idea of a “comprehensive” set of capture reagents begs the question of how many human proteins should be considered to represent the proteome in a way that is meaningful for biomedical research. Will a comprehensive affinity capture resource need to distinguish splicing variants? Post-translational modifications? Clearly, these considerations could have a large effect of the ultimate cost, not to mention the biological and technical issues involved in producing reagents against a “comprehensive” set. Within this workshop we would like to solicit advice about how to deal with these considerations in a practical sense, for example by balancing the costs with the utility, and/or by coming up with a framework for reasonable milestones for a comprehensive project.
The workshop will also need to provide other types of advice. NIH is aware that there are other similar efforts, at various scales and with various aims. How should NIH integrate its efforts with those going on elsewhere? What level of coordination is needed? In addition, NIH is aware that some methods are associated with private companies. How can NIH navigate between its need for producing a community resource, and the desirability of taking advantage of the best approaches, even where some may be associated with intellectual property constraints?
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