Efficient internalization into low-passage glioma cell lines using adenoviruses other than type 5: an approach for improvement of gene delivery to brain tumours.
There is a need for improvement of the commonly used adenovirus vectors based on serotype 5. This study was performed on three adenovirus serotypes with a CAR-binding motif (Ad4p, Ad5p and Ad17p) and three non-CAR-binding serotypes (Ad11p, Ad16p and Ad21p). The capacity of these alternative adenovirus vector candidates to deliver DNA into low-passage glioma cell lines from seven different donors was evaluated. The non-CAR-binding serotype Ad16p was the most efficient serotype with regard to import of its DNA, as well as initiation of hexon protein expression. Ad16p established hexon expression in 60-80 % of the cell population in gliomas from all donors tested. The other non-CAR-binding serotypes, Ad11p and Ad21p, showed hexon expression in 25-60 and 40-80 % of cells, respectively. The corresponding figure for the best CAR-binding serotype, Ad5p, was only 25-65 %, indicating greater variability between cells from different donors than serotype Ad16p had. The other CAR-binding serotypes, Ad4p and Ad17p, were refractory to some of the gliomas, giving a maximum of only 45 and 40 % hexon expression, respectively, in the most permissive cells. Interestingly, the transduction capacity of the CAR-binding serotypes was not correlated to the level of CAR expression on the cells.
Department of Virology, Umeå University, SE-901 85 Umeå, Sweden.
Johan
J
Skog
Department of Virology, Umeå University, SE-901 85 Umeå, Sweden.
Karin
K
Edlund
Department of Cell and Molecular Biology, Lund University, SE-223 62 Lund, Sweden.
Bengt
B
Widegren
Department of Neurosurgery, Lund University Hospital, SE-221 85 Lund, Sweden.
Leif G
LG
Salford
Department of Virology, Umeå University, SE-901 85 Umeå, Sweden.
Göran
G
Wadell
Department of Virology, Umeå University, SE-901 85 Umeå, Sweden.
Ya-Fang
YF
Mei
D000260:Adenoviruses, Human / Q000235:genetics*; D001932:Brain Neoplasms / Q000628:therapy*; D036022:Capsid Proteins / Q000032:analysis / Q000096:biosynthesis / Q000235:genetics; D045744:Cell Line, Tumor; D062727:Coxsackie and Adenovirus Receptor-Like Membrane Protein; D005434:Flow Cytometry; D015316:Genetic Therapy; D005822:Genetic Vectors; D005909:Glioblastoma; D006801:Humans; D017403:In Situ Hybridization; D011991:Receptors, Virus / Q000096:biosynthesis / Q000235:genetics; D012703:Serotyping
C568771:CLMP protein, human; D036022:Capsid Proteins; D062727:Coxsackie and Adenovirus Receptor-Like Membrane Protein; D011991:Receptors, Virus; C018315:hexon capsid protein, Adenovirus