Glycated AAV vectors: chemical redirection of viral tissue tropism.
Journal Article (Journal Article)
A chemical approach for selective masking of arginine residues on viral capsids featuring an exogenous glycation reaction has been developed. Reaction of adeno-associated viral (AAV) capsids with the α-dicarbonyl compound, methylglyoxal, resulted in formation of arginine adducts. Specifically, surface-exposed guanidinium side chains were modified into charge neutral hydroimidazolones, thereby disrupting a continuous cluster of basic amino acid residues implicated in heparan sulfate binding. Consequent loss in heparin binding ability and decrease in infectivity were observed. Strikingly, glycated AAV retained the ability to infect neurons in the mouse brain and were redirected from liver to skeletal and cardiac muscle following systemic administration in mice. Further, glycated AAV displayed altered antigenicity demonstrating the potential for evading antibody neutralization. Generation of unnatural amino acid side chains through capsid glycation might serve as an orthogonal strategy to engineer AAV vectors displaying novel tissue tropisms for gene therapy applications.
Full Text
Duke Authors
Cited Authors
- Horowitz, ED; Weinberg, MS; Asokan, A
Published Date
- April 20, 2011
Published In
Volume / Issue
- 22 / 4
Start / End Page
- 529 - 532
PubMed ID
- 21388193
Pubmed Central ID
- PMC3089942
Electronic International Standard Serial Number (EISSN)
- 1520-4812
Digital Object Identifier (DOI)
- 10.1021/bc100477g
Language
- eng
Conference Location
- United States