Modified adenoviral vectors ablated for coxsackievirus-adenovirus receptor, alphav integrin, and heparan sulfate binding reduce in vivo tissue transduction and toxicity.

@article{Koizumi2006ModifiedAV,
  title={Modified adenoviral vectors ablated for coxsackievirus-adenovirus receptor, alphav integrin, and heparan sulfate binding reduce in vivo tissue transduction and toxicity.},
  author={Naoya Koizumi and Kenji Kawabata and Fuminori Sakurai and Yoshiteru Watanabe and Takao Hayakawa and Hiroyuki Mizuguchi},
  journal={Human gene therapy},
  year={2006},
  volume={17 3},
  pages={
          264-79
        }
}
Coxsackievirus and adenovirus receptor (CAR), alphav integrins, and heparan sulfate glycosaminoglycans (HSGs) are the tropism determinants of adenoviral (Ad) vectors in vivo. For the development of a targeted Ad vector, its broad tropism needs to be blocked (or reduced). We have previously developed Ad vectors with ablation of CAR, alphav integrin, and HSG binding by mutation of the FG loop in the fiber knob (deletion of T489, A490, Y491, and T492 of the fiber protein), deletion of the RGD… Expand
Development of fiber-substituted adenovirus vectors containing foreign peptides in the adenovirus serotype 35 fiber knob
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It is indicated that HI loop is the most suitable domain to mediate a foreign peptide-dependent and CD46-independent transduction by incorporation of foreign peptides into the Ad35 fiber knob. Expand
Enhanced transduction efficiency of fiber-substituted adenovirus vectors by the incorporation of RGD peptides in two distinct regions of the adenovirus serotype 35 fiber knob.
TLDR
Fiber-mutant Ad5F35 vectors, by which foreign peptides can be simultaneously incorporated into both the FG and the HI loops of the Ad35 fiber knob, could be a promising gene delivery vehicle for various gene therapies, and could facilitate basic research efforts such as analyses of gene function. Expand
Replacement of native adenovirus receptor-binding sites with a new attachment moiety diminishes hepatic tropism and enhances bioavailability in mice.
TLDR
It is suggested that the targeted AdV design described here provides a promising platform for systemic in vivo gene delivery and displayed significantly reduced in vivo transduction in comparison with the native vector. Expand
Mutation of the Fiber Shaft Heparan Sulphate Binding Site of a 5/3 Chimeric Adenovirus Reduces Liver Tropism
TLDR
These studies set the stage for further investigations into the effects of the KKTK mutation and coagulation factor ablation in the context of 5/3 serotype chimerism and the putative disconnect between tumor transduction and transgene expression could prove useful in further understanding of adenovirus biology. Expand
Fiber and Penton Base Capsid Modifications Yield Diminished Adenovirus Type 5 Transduction and Proinflammatory Gene Expression with Retention of Antigen-Specific Humoral Immunity
TLDR
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Modification of pIX or hexon based on fiberless Ad vectors is not effective for targeted Ad vectors.
TLDR
This study is the first reported attempt to develop fiberless Ad vectors containing foreign ligands in the pIX or hexon region, and could provide basic information for the development of effective targeted Ad vectors. Expand
Ephrin A2 receptor targeting does not increase adenoviral pancreatic cancer transduction in vivo.
TLDR
Targeting the EphA2 receptor increases specificity of adenoviral transduction of human pancreatic cancer cells in vitro but fails to enhance Pancreas cancer transduction in vivo. Expand
Biodistribution and retargeting of FX-binding ablated adenovirus serotype 5 vectors.
TLDR
It is demonstrated that FX-binding ablated Ad5 predominantly localize to the liver and spleen 1 hour after injection; however, they had highly reduced liver transduction in both control and macrophage-depleted mice compared with Ad5. Expand
Adenovirus Serotype 5 Hexon Mediates Liver Gene Transfer
TLDR
It is shown that FX binds to the Ad5 hexon, not fiber, via an interaction between the FX Gla domain and hypervariable regions of the hexon surface, which reveals an unanticipated function for hexon in mediating liver gene transfer in vivo. Expand
Development and evaluation of a novel gene delivery vehicle composed of adenovirus serotype 35.
  • F. Sakurai
  • Biology, Medicine
  • Biological & pharmaceutical bulletin
  • 2008
TLDR
Ad vectors derived from other Ad serotypes different from Ad5, including Ad35, are expected to be gene delivery vehicles alternative to conventional Ad5 vectors. Expand
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