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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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organization
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 (PLoS)
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
2022-03-06 17:00:23
@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 (PLoS)}},
  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/files/3719879/4025478.pdf}},
  doi          = {{10.1371/journal.pone.0054952}},
  volume       = {{8}},
  year         = {{2013}},
}