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What noninvasive methods can enable functional and anatomical access to the vertebrate nervous system for cell-type specific delivery and optical control? The Gradinaru Research Laboratory engineers viral vectors and performs in vivo selection to generate AAV capsids that cross the blood–brain barrier and target distinct brain cell types. The group uses directed evolution and machine learning to develop high-fluxing opsins and trafficking strategies for safer, distant-light optical modulation. Researchers apply tissue clearing and whole-body clearing via vasculature perfusion to map neural circuitry and assess reagent distribution without sectioning. The lab performs multi-species directed evolution and receptor-discovery to identify primate-conserved factors such as carbonic anhydrase IV that enable BBB crossing by engineered AAVs.
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