Identification of a conserved receptor-binding site on the fiber proteins of CAR-recognizing adenoviridae.
The human adenovirus serotype 5 (Ad5) is used widely for applications in human gene therapy. Cellular attachment of Ad5 is mediated by binding of the carboxyl-terminal knob of its fiber coat protein to the Coxsackie adenovirus receptor (CAR) protein. However, Ad5 binding to CAR hampers the development of adenovirus vectors capable of specifically targeting (diseased) tissues or organs. Through sequence analysis and mutagenesis, a conserved receptor-binding region was identified on the side of three divergent CAR-binding knobs. The feasibility of simultaneous CAR ablation and redirection of an adenovirus to a new receptor is demonstrated.
Roelvink
P W
PW
Research and Development, GenVec Inc., 65 West Watkins Mill Road, Gaithersburg, MD 20879, USA. genecloner@genvec.com
Mi Lee
G
G
Einfeld
D A
DA
Kovesdi
I
I
Wickham
T J
TJ
D000260:Adenoviruses, Human / Q000737:chemistry* / Q000378:metabolism; D000595:Amino Acid Sequence; D001665:Binding Sites; D002213:Capsid / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D036022:Capsid Proteins; D002460:Cell Line; D017124:Conserved Sequence; D062727:Coxsackie and Adenovirus Receptor-Like Membrane Protein; D005822:Genetic Vectors; D006801:Humans; D008958:Models, Molecular; D016297:Mutagenesis, Site-Directed; D017354:Point Mutation; D011487:Protein Conformation; D017433:Protein Structure, Secondary; D011991:Receptors, Virus / Q000378:metabolism*; D017384:Sequence Deletion; D014162:Transfection; D014407:Tumor Cells, Cultured
C568771:CLMP protein, human; D036022:Capsid Proteins; D062727:Coxsackie and Adenovirus Receptor-Like Membrane Protein; D011991:Receptors, Virus; C018315:hexon capsid protein, Adenovirus