Peptide Modifications for Targeting AAV to the Brain
New short peptide sequences have been identified which are able to target AAV preferentially to the wild type and diseased brain.
UIRF Case #:08006
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Chen YH, Chang M, Davidson BL. Molecular signatures of disease brain endothelia provide new sites for CNS-directed enzyme therapy. Nat Med. 2009 Oct; 15(10): 1215-8.
Level of Development
General: Working Prototype
Researchers at the University of Iowa have discovered a series of peptide sequences that demonstrate selective tropism for endothelial cells of the brain vasculature when expressed on the surface of AAV. Furthermore, studies have shown that unique groups of peptide sequences target AAV vectors to wild type brain versus brains afflicted by lysosomal storage diseases. Wild type mouse brain cells were targeted by sequences within the family of PXXPS, SPXXP, TLH & QSXY; the brain cells in lysosomal storage disease mouse models lacking functional beta-glucuronidase were targeted by sequences within the family of LXSS, PFXG & SIXA; and the brain cells of lysosomal storage disease mouse models lacking tripeptidyl peptidase I (TPP-1) were targeted by the peptide GMNAFRA. Studies also showed that delivery of the missing functional gene through the utilization of these targeting peptides on AAV vectors resulted in the return of functional protein to the effected region and therapeutic benefit to the animal model.
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