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Adenovirus Serotype 5 Vectors with Tat-PTD Modified Hexon and Serotype 35 Fiber Show Greatly Enhanced Transduction Capacity of Primary Cell Cultures

Yu, Di ; Jin, Chuan ; Ramachandran, Mohanraj ; Xu, Jing ; Nilsson, Berith ; Korsgren, Olle ; Le Blanc, Katarina ; Uhrbom, Lene ; Forsberg-Nilsson, Karin and Westermark, Bengt , et al. (2013) In PLoS ONE 8(1).
Abstract
Recombinant adenovirus serotype 5 (Ad5) vectors represent one of the most efficient gene delivery vectors in life sciences. However, Ad5 is dependent on expression of the coxsackievirus-adenovirus- receptor (CAR) on the surface of target cell for efficient transduction, which limits it's utility for certain cell types. Herein we present a new vector, Ad5PTDf35, which is an Ad5 vector having serotype 35 fiber-specificity and Tat-PTD hexon-modification. This vector shows dramatically increased transduction capacity of primary human cell cultures including T cells, monocytes, macrophages, dendritic cells, pancreatic islets and exocrine cells, mesenchymal stem cells and tumor initiating cells. Biodistribution in mice following systemic... (More)
Recombinant adenovirus serotype 5 (Ad5) vectors represent one of the most efficient gene delivery vectors in life sciences. However, Ad5 is dependent on expression of the coxsackievirus-adenovirus- receptor (CAR) on the surface of target cell for efficient transduction, which limits it's utility for certain cell types. Herein we present a new vector, Ad5PTDf35, which is an Ad5 vector having serotype 35 fiber-specificity and Tat-PTD hexon-modification. This vector shows dramatically increased transduction capacity of primary human cell cultures including T cells, monocytes, macrophages, dendritic cells, pancreatic islets and exocrine cells, mesenchymal stem cells and tumor initiating cells. Biodistribution in mice following systemic administration (tail-vein injection) show significantly reduced uptake in the liver and spleen of Ad5PTDf35 compared to unmodified Ad5. Therefore, replication-competent viruses with these modifications may be further developed as oncolytic agents for cancer therapy. User-friendly backbone plasmids containing these modifications were developed for compatibility to the AdEasy-system to facilitate the development of surface-modified adenoviruses for gene delivery to difficult-to-transduce cells in basic, pre-clinical and clinical research. (Less)
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publishing date
type
Contribution to journal
publication status
published
subject
in
PLoS ONE
volume
8
issue
1
article number
e54952
publisher
Public Library of Science
external identifiers
  • wos:000315210400045
  • scopus:84872866042
  • pmid:23372800
ISSN
1932-6203
DOI
10.1371/journal.pone.0054952
language
English
LU publication?
yes
id
1a994119-f2a6-4e14-8fe1-b24ef3fda59b (old id 3674710)
date added to LUP
2016-04-01 14:00:27
date last changed
2020-06-10 03:09:21
@article{1a994119-f2a6-4e14-8fe1-b24ef3fda59b,
  abstract     = {Recombinant adenovirus serotype 5 (Ad5) vectors represent one of the most efficient gene delivery vectors in life sciences. However, Ad5 is dependent on expression of the coxsackievirus-adenovirus- receptor (CAR) on the surface of target cell for efficient transduction, which limits it's utility for certain cell types. Herein we present a new vector, Ad5PTDf35, which is an Ad5 vector having serotype 35 fiber-specificity and Tat-PTD hexon-modification. This vector shows dramatically increased transduction capacity of primary human cell cultures including T cells, monocytes, macrophages, dendritic cells, pancreatic islets and exocrine cells, mesenchymal stem cells and tumor initiating cells. Biodistribution in mice following systemic administration (tail-vein injection) show significantly reduced uptake in the liver and spleen of Ad5PTDf35 compared to unmodified Ad5. Therefore, replication-competent viruses with these modifications may be further developed as oncolytic agents for cancer therapy. User-friendly backbone plasmids containing these modifications were developed for compatibility to the AdEasy-system to facilitate the development of surface-modified adenoviruses for gene delivery to difficult-to-transduce cells in basic, pre-clinical and clinical research.},
  author       = {Yu, Di and Jin, Chuan and Ramachandran, Mohanraj and Xu, Jing and Nilsson, Berith and Korsgren, Olle and Le Blanc, Katarina and Uhrbom, Lene and Forsberg-Nilsson, Karin and Westermark, Bengt and Adamson, Rachel and Maitland, Norman and Fan, Xiaolong and Essand, Magnus},
  issn         = {1932-6203},
  language     = {eng},
  number       = {1},
  publisher    = {Public Library of Science},
  series       = {PLoS ONE},
  title        = {Adenovirus Serotype 5 Vectors with Tat-PTD Modified Hexon and Serotype 35 Fiber Show Greatly Enhanced Transduction Capacity of Primary Cell Cultures},
  url          = {https://lup.lub.lu.se/search/ws/files/3719879/4025478.pdf},
  doi          = {10.1371/journal.pone.0054952},
  volume       = {8},
  year         = {2013},
}