As our first major effort, we are developing well-validated, open-source monoclonal antibodies against every extracellular and secreted protein in humans. Currently, no such resource exists in academia or industry even though antibodies are critical enabling tools for protein science and drug discovery.
Our antibodies will be directed against human proteins and selected for cross-reactivity against mouse and zebrafish orthologs. This enables the same antibody to be used in both preclinical (animal) and clinical (human) studies.
The antibodies will be extensively characterized for specificity, cross-species reactivity, and utility in standard methods, including flow cytometry, immunoprecipitation, blotting, and immunohistochemistry. Validation will be conducted by the IPI, partner institutions, and individual investigators in crowd-sourced international workshops, modeled on the international Human Leucocyte Differentiation Antigens (HLDA) Workshops.
We will curate and make publicly available our antibodies and data, including DNA sequences, plasmids for protein expression, and molecular, cellular, and functional validation. By 2020, we will begin distributing antibodies in standard commercial formats.
The result will be a collection of tools and reagents for research that can interrogate most of the druggable proteome and transform biological study and therapeutic intervention.
Immunization-based methods of generating antibodies require animals and are limited by cost, slow turnaround, and the inability of the immune system to target proteins that are highly conserved between species.
To circumvent those constraints, we have created high-quality synthetic antibody libraries, consisting of more than one billion synthetic human antigen-binding fragments (Fabs) displayed on the surface of the yeast Saccharomyces cerevisiae. This well-established platform enables high-throughput antibody discovery without the need for animals. The platform also yields species cross-reactive antibodies that can target highly conserved, functionally important epitopes.
To facilitate engagement and leverage the collective wisdom of the wider scientific community, the IPI is soliciting nominations of target proteins and protein families for additional antibody discovery campaigns. We will prioritize nominations via scientific review by the IPI Scientific Advisory Board.
It is our aspiration to create antibodies and protein technologies that will open up a new landscape of protein science.
In conjunction with our flagship Antibody Initiative, we are piloting innovations in the use of affinity tags, cell line development, and directed evolution that will revamp the way we produce and purify proteins for antibody discovery and broader applications.
We will also build a library of all mouse and human extracellular and cell surface proteins, use them in all-on-all screens for receptor-ligand interactions, and distribute them as high quality individual proteins or protein family sets.
Stay tuned. There is still much to explore!