title: Validation of Heterodimeric TAT-NLS Peptide as a Gene Delivery Enhancer.
abstract: Cationic liposomes have been actively used as gene delivery vehicles despite their unsatisfactory efficiencies because of their relatively low toxicity. In this study, we designed novel heterodimeric peptides as nonviral gene delivery systems from TAT and NLS peptides using cysteine-to-cysteine disulfide bonds between the two. Mixing these heterodimeric peptides with DNA before mixing with lipofectamine resulted in higher transfection efficiencies in MCF-7 breast cancer cells than mixing unmodified TAT, NLS, and a simple mixture of TAT and NLS with DNA, but did not show an adverse effect on cell viability. In gel retardation assays, the DNA binding affinities of heterodimeric peptides were stronger than NLS but weaker than TAT. However, this enhancement was only observed when heterodimeric peptides were premixed with DNA before being mixed with lipofectamine. The described novel transfection-enhancing peptide system produced by the heterodimerization of TAT and NLS peptides followed by simple mixing with DNA, increased the gene transfer efficiency of cationic lipids without enhancing cytotoxicity.
authors.affiliation: Department of Physiology, College of Medicine, Yeungnam University, Daegu 705-717, Republic of Korea.
authors.forename: Kyung-Oh
authors.initials: KO
authors.lastname: Doh
mesh_terms: D045744:Cell Line, Tumor; D004220:Disulfides; D006801:Humans; D008055:Lipids; D019913:Nuclear Localization Signals / Q000235:genetics / Q000378:metabolism*; D055503:Protein Multimerization; D014162:Transfection / Q000379:methods*; D014170:Transformation, Genetic; D054322:tat Gene Products, Human Immunodeficiency Virus / Q000235:genetics / Q000378:metabolism*
chemical_list: D004220:Disulfides; D008055:Lipids; C086724:Lipofectamine; D019913:Nuclear Localization Signals; D054322:tat Gene Products, Human Immunodeficiency Virus