Journal of Microbiology and Biotechnology

  • 제21권8호
  • /
  • Pages.802-807
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  • 2011
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  • 1017-7825(pISSN)
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  • 1738-8872(eISSN)
한국미생물·생명공학회 (The Korean Society for Microbiology and Biotechnology)
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Enhancement of Gene Delivery Using Novel Homodimeric Tat Peptide Formed by Disulfide Bond

  • Lee, Soo-Jin (Department of Molecular Science and Technology, Ajou University) ;
  • Yoon, Sung-Hwa (Department of Molecular Science and Technology, Ajou University) ;
  • Doh, Kyung-Oh (Department of Physiology, College of Medicine, Yeungnam University)
  • 투고 : 2011.05.23
  • 심사 : 2011.06.01
  • 발행 : 2011.08.28
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초록

Cationic liposomes have been actively used as gene delivery vehicle because of their minimal toxicity, but their relatively low efficiency of gene delivery is the major disadvantage of these vectors. Recently, cysteine residue incorporation to HIV-1 Tat peptide increased liposomemediated transfection compared with unmodified Tat peptide. Therefore, we designed a novel modified Tat peptide having a homodimeric (Tat-CTHD, Tat-NTHD) and closed structure (cyclic Tat) simply by using the disulfide bond between cysteines to develop a more efficient and safe nonviral gene delivery system. The mixing of Tat-CTHD and Tat-NTHD with DNA before mixing with lipofectamine increased the transfection efficiency compared with unmodified Tat peptide and lipofectamine only in MCF-7 breast cancer cells and rat vascular smooth muscle cells. However, cyclic Tat did not show any improvement in the transfection efficiency. In the gel retardation assay, Tat-CTHD and Tat-NTHD showed more strong binding with DNA than unmodified Tat and cyclic Tat peptide. This enhancement was only shown when Tat-CTHD and Tat-NTHD were mixed with DNA before mixing with lipofectamine. The effects of Tat- CTHD and Tat-NTHD were also valid in the experiment using DOTAP and DMRIE instead of lipofectamine. We could not find any significant cytotoxicity in the working concentration and more usage of these peptides. In conclusion, we have designed a novel transfection-enhancing peptide by easy homodimerization of Tat peptide, and the simple mix of these novel peptides with DNA increased the gene transfer of cationic lipids more efficiently with no additional cytotoxicity.

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참고문헌

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  2. Efficient in vivo gene delivery using modified Tat peptide with cationic lipids vol.36, pp.7, 2014, https://doi.org/10.1007/s10529-014-1497-2
  3. Validation of Heterodimeric TAT-NLS Peptide as a Gene Delivery Enhancer vol.25, pp.6, 2011, https://doi.org/10.4014/jmb.1411.11074
  4. Cationic cell-penetrating peptides as vehicles for siRNA delivery vol.6, pp.4, 2011, https://doi.org/10.4155/tde.15.2
  5. Strategies to stabilize cell penetrating peptides for in vivo applications vol.6, pp.10, 2015, https://doi.org/10.4155/tde.15.51
  6. Engineering liposomal nanoparticles for targeted gene therapy vol.24, pp.8, 2011, https://doi.org/10.1038/gt.2017.41
  7. Synthesis and Preclinical Evaluation of the Fibrin-Binding Cyclic Peptide 18F-iCREKA: Comparison with Its Contrasted Linear Peptide vol.2019, pp.None, 2011, https://doi.org/10.1155/2019/6315954