Altering adenoviral tropism via click modification with ErbB specific ligands.
Methods for targeting oncolytic viruses can increase efficacy and accelerate development. Genetic engineering, the predominant method for changing vector tropism, is limited in scope and often represents the bottleneck for vector development. Metabolic incorporation of an unnatural azido sugar, O-GlcNAz, at a specific site on the adenoviral surface allows chemoselective attachment of affibodies for Her2 or EGF receptors. Modification with these high-affinity, high-selectivity proteins is straightforward and readily generalizable, demonstrates minimal impact on virus physiology, and affords significant increases in gene delivery to cancer cells. As a result, this method has significant potential to increase the efficacy of next-generation viral vectors.
Department of Chemistry, State University of New York at Stony Brook , Stony Brook, NY 11794-3400, USA.
Yoon Hyeun
YH
Oum
Isaac S
IS
Carrico
D000256:Adenoviridae / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D001386:Azides / Q000737:chemistry / Q000378:metabolism; D045744:Cell Line, Tumor; D057930:Click Chemistry; D066246:ErbB Receptors / Q000235:genetics / Q000378:metabolism*; D005688:Galactosamine / Q000737:chemistry / Q000378:metabolism; D018014:Gene Transfer Techniques; D005818:Genetic Engineering; D005822:Genetic Vectors / Q000235:genetics / Q000378:metabolism; D006801:Humans; D008024:Ligands; D008958:Models, Molecular; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000737:chemistry* / Q000235:genetics; D056189:Viral Tropism / Q000235:genetics
D001386:Azides; D066246:ErbB Receptors; D005688:Galactosamine; D008024:Ligands; D018719:Erb-b2 Receptor Tyrosine Kinases