Abstract: The present invention provides small molecules that act as binders for the BBB-crossing through the receptor carbonic anhydrase IV (CA-IV).

Abstract: Disclosed herein include novel blood-brain barrier (BBB)-crossing receptors on the BBB interface, targeting peptides and derivatives thereof capable of binding to the novel receptors, and related methods of using the receptors to increase the permeability of the BBB and to deliver an agent to a nervous system (e.g., CNS). In some embodiments, the BBB-crossing receptor is carbonic anhydrase IV. Disclosed herein also include recombinant adeno-associated viruses (rAAVs) with increased specificity and transduction efficiency across the BBB and related compositions and methods of treating various diseases and conditions.

Abstract: Disclosed herein include methods and compositions comprising variant AAV capsids. Variant capsid proteins, including variant capsid proteins with structure-guided deletion/substitution, tandem multimers, and/or variant capsid proteins with structure-guided deletion and C-terminal insertion, are provided in some embodiments. The variant capsid proteins disclosed herein are capable of assembling into a variant AAV capsid with an expanded size (e.g., diameter) and/or genetic cargo capacity. Methods of treating diseases and disorders using said rAAV are also disclosed.

Abstract: Disclosed herein include methods, compositions, and kits comprising variant AAV capsids. Variant capsid proteins, including guided variant capsid proteins, tandem multimers, and/or HI loop variant capsid proteins, are provided in some embodiments. The variant capsid proteins disclosed herein are capable of assembling into a variant AAV capsid with an expanded size (e.g., diameter) and/or genetic cargo capacity. Methods generating recombinant AAV (rAAV) with expanded capsids are provided. Methods of treating diseases and disorders using said rAAV are also disclosed.