Nonviral Gene Delivery by a Novel Protein Transduction Domain

Abstract

E-mail: pfjspark@plaza.snu.ac.krReceived May 28, 2013, Accepted June 3, 2013Gene therapy using nonviral gene delivery carriers has focused on the development and modification ofsynthetic carriers such as liposomes and polymers. Most polymers that are commercially used are takingadvantage of their polycationic character which allows not only strong ligand-DNA affinity but also competentcell penetration. Despite the relatively high transfection efficiencies, high cytotoxicity is continuously pointedout as one of the major shortcomings of polycationic polymers such as PEI. Studies on the utilization ofpeptides have therefore been carried out recently to overcome these problems. For these reasons, the humantranscription factor Hph-1, which is currently known as a protein transduction domain (PTD), was investigatedin this study to evaluate its potential as a gene delivery carrier. Although its transfection efficiency was about10-fold lower than PEI, it displayed almost no cytotoxicity even at concentrations as high as 100 µM. Hph-1was oxidatively polymerized to yield poly-Hph-1. The cell viability of poly-Hph-1 transfected U87MG andNIH-3T3 cells was almost as high as the control (untreated) groups, and the transfection efficiency was about10-fold higher than PEI. This study serves as a preliminary evaluation of Hph-1 and encourages furtherinvestigation.Key Words : Nonviral gene delivery, Protein transduction domain, Hph-1, Polycationic polymerIntroductionGene therapy has made great advancements over almosthalf a decade and is now at a stage where several genetherapy methods are now further investigated in clinicaltrials. Most of the gene delivery carriers, however, are viraland bear concerns in their actual clinical application ofhaving side effects and the uncertainty of complete safetyfrom lethal viral characteristics.