title: Construction of metabolically biotinylated adenovirus with deleted fiber knob as targeting vector.
abstract: Gene delivery vectors based on adenovirus, particularly human adenovirus serotype 5 (hAd5) have great potential for the treatment of variety of diseases. However, the tropism of hAd5 needs to be modified to achieve tissue- or cell- specific therapies for the successful application of this vector system to clinic. Here, we modified hAd5 tropism by replacing the fiber knob which contains the coxsackievirus B and adenovirus receptor (CAR)-binding sites with a biotin acceptor peptide, a truncated form of Propionibacterium shermanii 1.3 S transcarboxylase domain (PSTCD), to enable metabolically biotinylation of the virus. We demonstrate here that the new adenovirus no longer shows CAR-dependent cell uptake and transduction. When metabolically biotinylated and avidin-coated, it forms a nano-complex that can be retargeted to distinct cells using biotinylated antibodies. This vector may prove useful in the path towards achieving targeted gene delivery.
authors.affiliation: Proteogenomics Research Institute for Systems Medicine, 11107 Roselle St., San Diego, CA 92121, USA.
authors.forename: Yanzheng
authors.initials: Y
authors.lastname: Liu
authors.forename: Philippe
authors.initials: P
authors.lastname: Valadon
authors.forename: Jan E
authors.initials: JE
authors.lastname: Schnitzer
mesh_terms: D000260:Adenoviruses, Human / Q000235:genetics / Q000502:physiology*; D000818:Animals; D001710:Biotin / Q000378:metabolism*; D036022:Capsid Proteins / Q000235:genetics*; D019878:Carboxyl and Carbamoyl Transferases / Q000235:genetics; D062727:Coxsackie and Adenovirus Receptor-Like Membrane Protein; D017353:Gene Deletion; D018014:Gene Transfer Techniques; D015316:Genetic Therapy / Q000379:methods; D005822:Genetic Vectors; D006801:Humans; D011991:Receptors, Virus / Q000235:genetics; D011994:Recombinant Proteins / Q000235:genetics; D013194:Staining and Labeling / Q000379:methods; D056189:Viral Tropism
chemical_list: C568771:CLMP protein, human; D036022:Capsid Proteins; D062727:Coxsackie and Adenovirus Receptor-Like Membrane Protein; D011991:Receptors, Virus; D011994:Recombinant Proteins; C018315:hexon capsid protein, Adenovirus; D001710:Biotin; D019878:Carboxyl and Carbamoyl Transferases; C021580:Methylmalonyl-CoA carboxytransferase