Induction of apoptosis by gene transfer of human TRAIL mediated by arginine-rich intracellular delivery peptides.

ABSTRACT

BACKGROUND: Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL), a member of the tumor necrosis factor (TNF) family, has shown potent and high selective antitumor activity as a promising therapy for cancer. We have developed an arginine-rich intracellular delivery (AID) peptide-mediated system for nontoxic and efficient gene transfer in cells. MATERIALS AND METHODS: To evaluate antitumor activity and therapeutic potential of TRAIL gene, a bifunctional expression plasmid was constructed encoding the secretory signal peptide of human immunoglobulin kappa (Ig kappa) light chain, the extracellular portion (amino acids 95-281) of human TRAIL and the humanized green fluorescent protein (GFP). RESULTS: We demonstrated that AID peptides were able to effectively deliver TRAIL gene into human lung carcinoma A549 cells. Soluble TRAIL-GFP protein purified from media after gene delivery was further evaluated regarding selective induction of apoptosis in cells. CONCLUSION: AID peptide-mediated DNA transfer provides a potential and convenient tool in nonviral gene therapy.