Novel biologics targeting the P2X7 ion channel

Abstract

Targeting the P2X7 ion channel, a danger sensor for extracellular nucleotides, improves outcomes in models of inflammation, cancer, and brain-diseases. Antibodies and nanobodies have been developed that antagonize or potentiate gating of P2X7. Their potential advantages over small-molecule drugs include high specificity, lower off-target effects, and tunable in vivo half-life. Genetic fusion of P2X7-specific biologics to binding modules may enable targeting of specific cell subsets. Besides directly modulating P2X7 function, antibodies can also initiate specific depletion of P2X7-expressing cells. Adeno-associated viral vectors (AAV) can be used to express P2X7-specific antibodies in vivo to achieve long-lasting biological effects. Furthermore, if successfully targeted to P2X7-expressing cells, AAVs may enable modulation of the function of P2X7-expressing immune cells via encoded transgenic RNA or proteins.