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Göteborgs universitets publikationer

Re-targeted adenovirus vectors with dual specificity; binding specificities conferred by two different Affibody molecules in the fiber.

Författare och institution:
Susanna Myhre (Institutionen för biomedicin, avdelningen för mikrobiologi och immunologi); Petra Henning (Institutionen för biomedicin, avdelningen för mikrobiologi och immunologi); M Friedman (-); S Ståhl (-); Leif Lindholm (Institutionen för biomedicin, avdelningen för mikrobiologi och immunologi); Maria K Magnusson (Institutionen för biomedicin, avdelningen för mikrobiologi och immunologi)
Publicerad i:
Gene therapy, 16 ( 2 ) s. 252-61
Artikel, refereegranskad vetenskaplig
Sammanfattning (abstract):
Vectors based on Adenovirus type 5 (Ad5) are among the most common vectors in cancer gene therapy trials to date. However, for increased efficiency and safety, Ad5 should be de-targeted from its native receptors and re-targeted to a tumor antigen. We have described earlier an Ad5 vector genetically re-targeted to the tumor antigen HER2/neu by a dimeric version of the Affibody molecule ZH inserted in the HI-loop of the fiber knob of a coxsackie and adenovirus receptor-binding ablated fiber. This virus showed almost wild-type growth characteristics and infected cells through HER2/neu. Here we generate vectors with double specificity by incorporating two different Affibody molecules, ZH (HER2/neu-binding) and ZT (Taq polymerase-binding), at different positions relative to one another in the HI-loop. Receptor-binding studies together with viral production and gene transfer assays showed that the recombinant fiber with ZT in the first position and ZH in the second position (ZTZH) bound to both its targets, whereas surprisingly, the fiber with ZHZT was devoid of binding to HER2/neu. Hence, it is possible to construct a recombinant adenovirus with dual specificity after evaluating the best position for each ligand in the fiber knob.
Ämne (baseras på Högskoleverkets indelning av forskningsämnen):
Medicinska grundvetenskaper ->
Mikrobiologi inom det medicinska området
Adenoviridae, genetics, physiology, Cell Line, Gene Targeting, methods, Gene Therapy, methods, Genetic Vectors, genetics, Humans, Ligands, Protein Multimerization, Recombinant Fusion Proteins, biosynthesis, Recombination, Genetic, Solubility, Transfection, Virus Replication
Postens nummer:
Posten skapad:
2010-01-19 10:13
Posten ändrad:
2011-01-20 09:59

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