Generation of Antibodies That Are Externally Acting Isoform-Specific Inhibitors of Ion Channels

There is demand for isoform-specific ion channel inhibitors as tools to investigate the biology of �endogenous ion channels and validate them as targets in drug discovery programs. There is also hope that such inhibitors may be new therapeutic agents or provide the foundation for such agents. However, in practice, it is commonly experienced that inhibitors lack sufficient specificity, fail to distinguish between members of a class of ion channel, or have other (non-ion channel) off-target effects. Due to their extraordinary specificity, antibodies offer a potentially attractive strategy for overcoming these problems. Inhibitory antibodies acting at the extracellular face of ion channels are particularly attractive because there is enhanced possibility for specificity and intracellular delivery methods are not required. Here we describe experience with such an antibody approach and methodology for generating agents based on anti-peptide polyclonal antibodies.