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Engraftment of a galactose receptor footprint onto adeno-associated viral capsids improves transduction efficiency.

J Biol Chem. 2013; 
Shen S, Horowitz ED, Troupes AN, Brown SM, Pulicherla N, Samulski RJ, Agbandje-McKenna M, Asokan A.
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Custom Vector Construction … This mutant capsid sequence was designed with the use of VectorNTI and was synthesized (GenScript) into pUC57 (referred to as pUC57 9-2 mutant cap). Restriction digests, BsiWI to NotI; BsiWI to XmaI; and XmaI to NotI of … Get A Quote

摘要

New viral strains can be evolved to recognize different host glycans through mutagenesis and experimental adaptation. However, such mutants generally harbor amino acid changes that affect viral binding to a single class of carbohydrate receptors. We describe the rational design and synthesis of novel, chimeric adeno-associated virus (AAV) strains that exploit an orthogonal glycan receptor for transduction. A dual glycan-binding AAV strain was first engineered as proof of concept by grafting a galactose (Gal)-binding footprint from AAV serotype 9 onto the heparan sulfate-binding AAV serotype 2. The resulting chimera, AAV2G9, continues to bind heparin affinity columns but interchangeably exploits Gal and heparan ... More

关键词

Adeno-associated Virus; Carbohydrate; Cell Surface Receptor; Gene Therapy; Protein Engineering; Virus Entry