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

Bioscience Reports
Shihai LiuHaibin Xia

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.

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Citations

Jan 10, 2012·Journal of Biotechnology·Bingyan DiHaibin Xia
Feb 22, 2005·Advanced Drug Delivery Reviews·Jehangir S Wadia, Steven F Dowdy
Jan 2, 2007·Journal of Controlled Release : Official Journal of the Controlled Release Society·Ashok ChauhanMahavir Singh
Jun 7, 2013·Therapeutic Delivery·Nabil A AlhakamyJoshua D Ramsey

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Methods Mentioned

BETA
PCR
FACS
electron microscopy

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