scholarly journals Protein Transduction Domains Fused to Virus Receptors Improve Cellular Virus Uptake and Enhance Oncolysis by Tumor-Specific Replicating Vectors

2004 ◽  
Vol 78 (24) ◽  
pp. 13743-13754 ◽  
Author(s):  
Florian Kühnel ◽  
Bernd Schulte ◽  
Thomas Wirth ◽  
Norman Woller ◽  
Sonja Schäfers ◽  
...  
Keyword(s):  
Viral Vectors ◽  
Protein Transduction ◽  
Virus Binding ◽  
Adenoviral Infection ◽  
Protein Transduction Domains ◽  
Oncolytic Therapy ◽  
Uptake Rates ◽  
Immunodeficiency Virus ◽  
Transactivator Of Transcription ◽  
Adenovirus Receptor

ABSTRACT Expression of cellular receptors determines viral tropism and limits gene delivery by viral vectors. Protein transduction domains (PTDs) have been shown to deliver proteins, antisense oligonucleotides, liposomes, or plasmid DNA into cells. In our study, we investigated the role of several PTD motifs in adenoviral infection. When physiologically expressed, a PTD from human immunodeficiency virus transactivator of transcription (Tat) did not improve adenoviral infection. We therefore fused PTDs to the ectodomain of the coxsackievirus-adenovirus receptor (CARex) to attach PTDs to adenoviral fiber knobs. CARex-Tat and CARex-VP22 allowed efficient adenoviral infection in nonpermissive cells and significantly improved viral uptake rates in permissive cells. Dose-dependent competition of CARex-PTD-mediated infection using CARex and inhibition experiments with heparin showed that binding of CARex-PTD to both adenoviral fiber and cellular glycosaminoglycans is essential for the improvement of infection. CARex-PTD-treated adenoviruses retained their properties after density gradient ultracentrifugation, indicating stable binding of CARex-PTD to adenoviral particles. Consequently, the mechanism of CARex-PTD-mediated infection involves coating of the viral fiber knobs by CARex-PTD, rather than placement of CARex domains on cell surfaces. Expression of CARex-PTDs led to enhanced lysis of permissive and nonpermissive tumor cells by replicating adenoviruses, indicating that CARex-PTDs are valuable tools to improve the efficacy of oncolytic therapy. Together, our study shows that CARex-PTDs facilitate gene transfer in nonpermissive cells and improve viral uptake at reduced titers and infection times. The data suggest that PTDs fused to virus binding receptors may be a valuable tool to overcome natural tropism of vectors and could be of great interest for gene therapeutic approaches.

scholarly journals Enhanced skin penetration of P20 phosphopeptide using protein transduction domains

2008 ◽  
Vol 68 (2) ◽  
pp. 441-445 ◽  
Author(s):  
Luciana B. Lopes ◽  
Elizabeth Furnish ◽  
Padmini Komalavilas ◽  
Brandon L. Seal ◽  
Alyssa Panitch ◽  
...  
Keyword(s):  
Skin Penetration ◽  
Protein Transduction ◽  
Protein Transduction Domains

Taking the Cell by Stealth or Storm? Protein Transduction Domains (PTDs) as Versatile Vectors for Delivery

2002 ◽  
Vol 21 (12) ◽  
pp. 879-894 ◽  
Author(s):  
Marie A. Bogoyevitch ◽  
Tulene S. Kendrick ◽  
Dominic C.H. Ng ◽  
Renae K. Barr
Keyword(s):  
Protein Transduction ◽  
Protein Transduction Domains

scholarly journals A ubiquitin-based assay for the cytosolic uptake of protein transduction domains

2005 ◽  
Vol 11 (2) ◽  
pp. 205-214 ◽  
Author(s):  
Fabien Loison ◽  
Philippe Nizard ◽  
Tony Sourisseau ◽  
Pascale Le Goff ◽  
Laure Debure ◽  
...  
Keyword(s):  
Protein Transduction ◽  
Protein Transduction Domains

scholarly journals Comparative study on transduction and toxicity of protein transduction domains

2008 ◽  
Vol 153 (6) ◽  
pp. 1143-1152 ◽  
Author(s):  
T Sugita ◽  
T Yoshikawa ◽  
Y Mukai ◽  
N Yamanada ◽  
S Imai ◽  
...  
Keyword(s):  
Comparative Study ◽  
Protein Transduction ◽  
Protein Transduction Domains

scholarly journals Antibody Mediated Transduction of Therapeutic Proteins into Living Cells

2005 ◽  
Vol 5 ◽  
pp. 782-788 ◽  
Author(s):  
James E. Hansen ◽  
Richard H. Weisbart ◽  
Robert N. Nishimura
Keyword(s):  
Therapeutic Proteins ◽  
Disease Process ◽  
Antibody Fragment ◽  
Living Cells ◽  
Cell Penetrating Peptides ◽  
Biologically Active ◽  
Protein Transduction ◽  
Protein Therapy ◽  
Single Chain ◽  
Protein Transduction Domains

Protein therapy refers to the direct delivery of therapeutic proteins to cells and tissues with the goal of ameliorating or modifying a disease process. Current techniques for delivering proteins across cell membranes include taking advantage of receptor-mediated endocytosis or using protein transduction domains that penetrate directly into cells. The most commonly used protein transduction domains are small cell-penetrating peptides derived from such proteins as the HIV-1 Tat protein. A novel protein transduction domain developed as the single chain fragment (Fv) of a murine anti-DNA autoantibody, mAb 3E10, has recently been developed and used to deliver biologically active proteins to living cellsin vitro. This review will provide a brief overview of the development of the Fv fragment and provide a summary of recent studies using Fv to deliver therapeutic peptides and proteins (such as a C-terminal p53 peptide, C-terminal p53 antibody fragment, full-length p53, and micro-dystrophin) to cells.

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