Chemical BBB shuttle targets CA-IV for potent brain delivery

Former CLOVER Research Scientists and Gradinaru lab alumns Xiaozhe Ding and Xinhong Chen led a multidisciplinary effort with fellow co-first authors from the Reisman lab at Caltech that generated a small molecule shuttle to efficiently deliver biological cargo across the blood-brain barrier (BBB) of mice and non-human primates. This technology, called BrainCAB, utilizes the BBB transcytosis receptor carbonic anhydrase IV (CA-IV), which was identified as the receptor for some of the most potent brain-enhanced AAVs for mouse and, more recently, was used to develop human brain-targeted AAVs. The current work demonstrates that CA-IV is also capable of potent and specific delivery of non-viral cargo to the brain. Coauthors include current and former CLOVER staff Erin Sullivan, Fiona Ristic, Bill Kavvathas, Yaping Lei, and Tim Shay.

For more details read the feature in Caltech news and catch the full story in Nature Chemical Biology.

Congratulations Xiaozhe, Xinhong, and the team!