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

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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.

Details

Authors
  • Di Yu
  • Chuan Jin
  • Mohanraj Ramachandran
  • Jing Xu
  • Berith Nilsson
  • Olle Korsgren
  • Katarina Le Blanc
  • Lene Uhrbom
  • Karin Forsberg-Nilsson
  • Bengt Westermark
  • Rachel Adamson
  • Norman Maitland
  • Xiaolong Fan
  • Magnus Essand
Organisations
Research areas and keywords

Subject classification (UKÄ) – MANDATORY

  • Hematology
Original languageEnglish
Article numbere54952
JournalPLoS ONE
Volume8
Issue number1
Publication statusPublished - 2013
Publication categoryResearch
Peer-reviewedYes

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