Protein transduction: an alternative to genetic intervention?

Ford, KG; Be, Souberbielle; Darling, David; Farzaneh, Farzin

doi:10.1038/sj.gt.3301383

Cited by 133 publications

(104 citation statements)

References 30 publications

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“…20 Protein transduction domains (PTDs) are short peptides which can freely pass through cell membrane independent of classical receptors or endocytosis. 21 Although the detailed mechanism of this type of transduction is still unclear, PTDs can be used as a carrier to deliver macromolecules, such as functional proteins into cells, even at whole body scale. 22,23 Among PTDs, the PTD containing 11 amino acids (peptide sequence: YGRKKRRQRRR) from HIV trans-activator (TAT/PTD) protein is the most extensively studied 24,25 peptide.…”

Section: Introductionmentioning

confidence: 99%

A cell penetrating heme oxygenase protein protects heart graft against ischemia/reperfusion injury

Ma¹,

Lau

Obed³

et al. 2008

Gene Ther

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Ischemia/reperfusion (I/R) injury is an unavoidable barrier that significantly affects outcome of solid organ transplantation. Here, we establish a protein transduction system to extend graft preservation time and to prevent I/R injury in heart transplantation. We generated a recombinant heme oxygenase-1 (HO-1) protein containing a modified protein transduction domain (PTD). PTD could cross cover cell membrane and carry target molecule to parenchymal cells of cold-preserved heart grafts. The newly generated PTD-HO-1 protein localized mainly in subcellular membrane organelle and nucleus after delivery that significantly prolonged cold preservation of heart grafts. This effect was associated with significantly less endothelial cell activation, less neutrophil and macrophage infiltration in PTD-HO-1-transduced heart grafts after reperfusion as compared with controls. In addition, transduction of PTD-HO-1 protein to heart graft significantly suppressed the I/R injury-associated myocardiocyte apoptosis. The infarct areas of heart graft after I/R injury were significantly reduced after PTD-HO-1 protein treatment. We show here for the first time that PTD can maintain its biological activities during cold preservation. Transduction of cell penetrating HO-1 protein significantly prolongs the cold preservation time and protects the graft from the I/R injury. This approach represents a novel method for the improvement of the overall outcome of organ transplantation.

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Section: Introductionmentioning

confidence: 99%

A cell penetrating heme oxygenase protein protects heart graft against ischemia/reperfusion injury

Ma¹,

Lau

Obed³

et al. 2008

Gene Ther

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“…21 Major drawbacks of these methods are the requirement for protein purification prior to transduction, possible interference of peptides carriers, like, eg an HIV-TAT-derived peptide, with cellular gene expression or inadequate subcellular targeting of the transduced protein (reviewed in ref. 22). DB of HCMV may provide an alternative to these techniques.…”

mentioning

confidence: 99%

Protein delivery by subviral particles of human cytomegalovirus

Pepperl-Klindworth¹,

Frankenberg²,

Riegler

et al. 2003

Gene Ther

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Direct protein delivery is an emerging technology in vaccine development and gene therapy. We could previously show that subviral dense bodies (DB) of human cytomegalovirus (HCMV), a beta-herpesvirus, transport viral proteins into target cells by membrane fusion. Thus these non-infectious particles provide a candidate delivery system for the prophylactic and therapeutic application of proteins. Here we provide proof of principle that DB can be modified genetically. A 55 kDa fusion protein consisting of the green fluorescent protein and the neomycin phosphotransferase could be packed in and delivered into cells by recombinant DB in a functional fashion. Furthermore, transfer of protein into fibroblasts and dendritic cells by DB was efficient, leading to exogenous loading of the MHC-class I antigen presentation pathway. Thus, DB may be a promising basis for the development of novel vaccine strategies and therapeutics based on recombinant polypeptides.

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“…Recently, several peptides have been identified with the ability to deliver proteins across the cell membrane (Schwarze et al, 2000;Ford et al, 2001). One of the most commonly used protein transduction systems is a positively charged domain (aa 47-57; YGRKKRRQRRR) found in the HIV-1 trans-activator protein TAT, the TAT protein transduction domain (TAT-PTD).…”

Section: Introductionmentioning

confidence: 99%