Targeting of Adenoviral Gene Therapy Vectors: The Flexibility of Chemical and Molecular Conjugation

2003 ◽  
pp. 123-141
Author(s):  
Hidde J. Haisma ◽  
Marianne G. Rots
Keyword(s):  
Gene Therapy ◽  
Gene Therapy Vectors ◽  
Adenoviral Gene Therapy

scholarly journals Targeting adenoviral gene therapy vectors towards human endometrial cells

2009 ◽  
Vol 92 (3) ◽  
pp. S123
Author(s):  
E.-E.R. Othman ◽  
D. Hornung ◽  
B. El-Helw ◽  
H.A. El-Maghraby ◽  
D.T. Curiel ◽  
...  
Keyword(s):  
Gene Therapy ◽  
Endometrial Cells ◽  
Gene Therapy Vectors ◽  
Adenoviral Gene Therapy

scholarly journals Phylogeny and primary structure analysis of fiber shafts of all human adenovirus types for rational design of adenoviral gene-therapy vectors

2009 ◽  
Vol 90 (12) ◽  
pp. 2849-2854 ◽  
Author(s):  
Sebastian Darr ◽  
Ijad Madisch ◽  
Sören Hofmayer ◽  
Fabienne Rehren ◽  
Albert Heim
Keyword(s):  
Gene Therapy ◽  
Rational Design ◽  
Amino Acid Sequence Identity ◽  
Species Concept ◽  
Hot Spot ◽  
Human Adenovirus ◽  
Conserved Sequence ◽  
Gene Therapy Vectors ◽  
Sequence Stretch ◽  
Adenoviral Gene Therapy

The fiber shaft of human adenoviruses (HAdVs) is essential for bringing the penton base into proximity to the secondary cellular receptor. Fiber shaft sequences of all 53 HAdV types were studied. Phylogeny of the fiber shaft revealed clustering corresponding to the HAdV species concept. An intraspecies recombination hot spot was found at the shaft/knob boundary, a highly conserved sequence stretch. For example, HAdV-D20 clustered with HAdV-D23 in the fiber shaft, but with HAdV-D47 in the fiber knob. Although all shafts exhibited the typical pseudorepeats, amino acid sequence identity was found to be as high as 92 % (interspecies) and 54 % (intraspecies). In contrast to a previous study, a flexibility motif (KXGGLXFD/N) was found in eight HAdV-D types, whereas the putative heparan sulfate-binding site (KKTK) was only found in species HAdV-C. Our results suggest that pseudotyping of gene-therapy vectors at the shaft/knob boundary is feasible, but that flexibility data of shafts should be considered.

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