Carbonic anhydrase IV (CA-IV)

Carbonic anhydrase IV (CA-IV) is a glycosylphosphatidylinositol (GPI)-anchored enzyme primarily expressed on the luminal surface of brain capillary endothelial cells, where it plays a critical role in pH regulation and bicarbonate homeostasis. In the context of advanced gene therapy, CA-IV has been identified as a key cell-surface receptor that facilitates the crossing of the blood-brain barrier (BBB) by engineered adeno-associated virus (AAV) capsids, such as those developed by Capsida Biotherapeutics. These proprietary capsids utilize CA-IV to undergo receptor-mediated transcytosis, allowing for broad and efficient delivery of genetic cargo to neurons and astrocytes throughout the central nervous system. By targeting CA-IV, these next-generation vectors can achieve high levels of CNS transduction at significantly lower systemic doses compared to wild-type AAVs, thereby reducing the risk of liver toxicity and other off-target effects. This mechanism is central to the development of disease-modifying therapies for neurological disorders like STXBP1-related encephalopathy and Parkinson's disease.

Other names

CA-IVCA4Carbonate dehydratase IVNR004Blood-brain barrier transcytosis receptor