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


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.


CONCLUSIONS
AID peptide-mediated DNA transfer provides a potential and convenient tool in nonviral gene therapy.
Li
Jheng-Fong
JF
Department of Natural Resources and Environmental Studies, National Dong Hwa University, Hualien 97401, Taiwan, ROC.
Huang
Yuliana
Y
Chen
Rong-Long
RL
Lee
Han-Jung
HJ
D017209:Apoptosis; D001120:Arginine; D045744:Cell Line, Tumor; D016503:Drug Delivery Systems; D005434:Flow Cytometry; D015316:Genetic Therapy; D049452:Green Fluorescent Proteins / Q000235:genetics; D006801:Humans; D020287:In Situ Nick-End Labeling; D009369:Neoplasms / Q000628:therapy*; D010455:Peptides / Q000008:administration & dosage*; D010957:Plasmids; D053221:TNF-Related Apoptosis-Inducing Ligand / Q000235:genetics*
D010455:Peptides; D053221:TNF-Related Apoptosis-Inducing Ligand; C505653:TNFSF10 protein, human; D049452:Green Fluorescent Proteins; D001120:Arginine