Genetically modified adenoviral vector with the protein transduction domain of Tat improves gene transfer to CAR-deficient cells

Shihai Liu, Qinwen Mao, Weifeng Zhang, Xiaojing Zheng, Ye Bian, Dongyang Wang, Huijin Li, Lihong Chai, Junli Zhao, Haibin Xia*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

11 Scopus citations

Abstract

The transduction efficiency of Ad (adenovirus) depends, to some extent, on the expression level of CAR (coxsackievirus and Ad receptor) of a target cell. The low level of CAR on the cell surface is a potential barrier to efficient gene transfer. To overcome this problem, PTD.AdeGFP (where eGFP is enhanced green fluorescent protein) was constructed by modifying the HI loop of Ad5 (Ad type 5) fibre with the Tat (trans-activating) PTD (protein transduction domain) derived from HIV. The present study showed that PTD.AdeGFP significantly improved gene transfer to multiple cell types deficient in expression of CAR. The improvement in gene transfer was not the result of charge-directed binding between the virus and the cell surface. Although PTD.AdeGFP formed aggregates, it infected target cells in a manner different from AdeGFP aggregates precipitated by calcium phosphate. In addition, PTD.AdeGFP was able to transduce target cells in a dynamin-independent pathway. The results provide some new clues as to how PTD.AdeGFP infects target cells. This new vector would be valuable in gene-function analysis and for gene therapy in cancer.

Original languageEnglish (US)
Pages (from-to)103-109
Number of pages7
JournalBioscience Reports
Volume29
Issue number2
DOIs
StatePublished - Apr 2009

Keywords

  • Adenovirus (Ad)
  • Cancer
  • Fibre protein
  • Gene delivery
  • Protein transduction domain (PTD)
  • Tat

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

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