Methods and compositions for treating brain diseases
The present disclosure provides targeting peptides and vectors containing a sequence that encodes targeting peptides that deliver agents to the brain.
1. A modified adeno-associated virus (AAV) capsid protein comprising a targeting peptide WPFYGTP (SEQ ID NO:29), as expressed in an amino to carboxy orientation or in a carboxy to amino orientation, wherein the targeting peptide targets an AAV to mucopolysaccharide (MPS) brain vascular endothelium.
2. The capsid protein of claim 1 , wherein the AAV is AAV2.
3. A nucleic acid sequence encoding the modified capsid protein of claim 1 .
4. An AAV virus containing the capsid protein of claim 1 .
5. A viral vector comprising a nucleic acid encoding the capsid protein of claim 1 .
6. A cell comprising the viral vector of claim 5 .
7. A method of treating a disease in a mammal comprising administering
(a) a viral vector comprising a nucleic acid encoding a capsid protein comprising a targeting peptide WPFYGTP (SEQ ID NO:29), as expressed in an amino to carboxy orientation or in a carboxy to amino orientation, wherein the targeting peptide targets an AAV to mucopolysaccharide (MPS) brain vascular endothelium, or
(b) a cell comprising a viral vector comprising a nucleic acid encoding a capsid protein comprising a targeting peptide WPFYGTP (SEQ ID NO:29), as expressed in an amino to carboxy orientation or in a carboxy to amino orientation, wherein the targeting peptide targets an AAV to mucopolysaccharide (MPS) brain vascular endothelium.
8. A method to deliver an agent to the central nervous system of a subject, comprising transducing vascular endothelial cells with the viral vector of claim 5 so that the transduced vascular endothelial cells express the agent and deliver the agent to the central nervous system of the subject.