Membrane proteins control the flow of information, nutrients, and signals through the cell membrane, and are the targets for 59% of FDA-approved drugs. Monoclonal antibodies (MAbs) that target membrane proteins can be exceptionally valuable in research, diagnostic, and therapeutic applications, but for the vast majority of membrane proteins there are either no MAbs at all or only poor quality antibodies with limited application. The need for high quality MAbs against membrane proteins has been recognized by industry and the NIH, but efforts to identify such MAbs are limited by the difficulty in expressing and purifying membrane proteins in exogenous systems and by conventional MAb isolation strategies that focus on one target at a time. A novel approach to identify membrane protein MAbs in a high-throughput manner is needed to derive MAbs against the entire human membrane proteome. Here we propose a technology that can be used to rapidly isolate high quality MAbs against membrane proteins to fulfill this unmet need.
This proposal will contribute to public health and the cure of human disease by isolating the largest collection of high quality MAbs against membrane proteins currently available. MAbs that target membrane proteins can be exceptionally valuable in research, diagnostic, and therapeutic applications, but for the vast majority of membrane proteins there are either no MAbs at all or only poor quality antibodies with limited application.
| Tucker, David F; Sullivan, Jonathan T; Mattia, Kimberly-Anne et al. (2018) Isolation of state-dependent monoclonal antibodies against the 12-transmembrane domain glucose transporter 4 using virus-like particles. Proc Natl Acad Sci U S A 115:E4990-E4999 |
