title: Gene delivery using a derivative of the protein transduction domain peptide, K-Antp.
abstract: Due to their intracellular permeability, protein transduction domains (PTDs) have been widely used to deliver proteins and peptides to mammalian cells. However, their performance in gene delivery has been relatively poor. To improve the efficiency of PTD-mediated gene delivery, we synthesized a new peptide, KALA-Antp (K-Antp), which contains the sequences for PTD of the third alpha-helix of Antennapedia (Antp) homeodomain and the fusogenic peptide KALA. In this configuration, Antp is designed to provide the cell permeation capacity and nuclear localization signal, while the KALA moiety to promote cellular entry of the peptide-DNA complex. An optimal K-Antp/DNA formula was nearly 400-600 fold more efficient than Antp or poly-lysine-Antp (L-Antp) in gene delivery, and comparable or superior to a commercial liposome. The K-Antp-mediated plasmid DNA transfection not only exhibited temperature sensitivity, reflecting the involvement of an endocytosis-mediated gene transfer mechanism similar to other known PTDs, but also temperature insensitivity, suggesting the role of an energy-independent mechanism. Incorporation of an endosomolytic polymer polyethylenimine (PEI) into the system or treatment with chloroquine further increased the efficiency of K-Antp-mediated gene delivery. These results demonstrate the potential of the combinatorial use of KALA, Antp and PEI in the development of efficient PTD-derived gene carriers.
authors: Medical Genomics Research Center, Korea Research Institute of Bioscience and Biotechnology, 111 Gwahangno, Yuseong-gu, Daejeon 305-806, Republic of Korea.
authors: Sang-Hyun
authors: SH
authors: Min
authors: Dong Min
authors: DM
authors: Kim
authors: Mi Na
authors: MN
authors: Kim
authors: Jiang
authors: J
authors: Ge
authors: Dong Chul
authors: DC
authors: Lee
authors: In Young
authors: IY
authors: Park
authors: Kyung Chan
authors: KC
authors: Park
authors: Ji-Sook
authors: JS
authors: Hwang
authors: Cheong-Weon
authors: CW
authors: Cho
authors: Young Il
authors: YI
authors: Yeom
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D045744:Cell Line, Tumor; D004247:DNA / Q000235:genetics; D011992:Endosomes / Q000378:metabolism; D018014:Gene Transfer Techniques; D051379:Mice; D008969:Molecular Sequence Data; D010455:Peptides / Q000737:chemistry* / Q000378:metabolism*; D010957:Plasmids / Q000235:genetics; D011108:Polymers / Q000378:metabolism; D017434:Protein Structure, Tertiary; D013696:Temperature; D014162:Transfection
chemical_list: C548457:KALA-Antp peptide; D010455:Peptides; D011108:Polymers; D004247:DNA