Bulletin of the Korean Chemical Society

  • 제34권9호
  • /
  • Pages.2589-2593
  • /
  • 2013
  • /
  • 0253-2964(pISSN)
  • /
  • 1229-5949(eISSN)
대한화학회 (Korean Chemical Society)
권호 표지
DOI QR코드

DOI QR Code

Nonviral Gene Delivery by a Novel Protein Transduction Domain

  • An, Songhie (Department of Chemistry, Seoul National University) ;
  • Park, Jong-Sang (Department of Chemistry, Seoul National University)
  • 투고 : 2013.05.28
  • 심사 : 2013.06.03
  • 발행 : 2013.09.20
PDF 다운로드
⟨ 이전 논문 다음 논문 ⟩

초록

Gene therapy using nonviral gene delivery carriers has focused on the development and modification of synthetic carriers such as liposomes and polymers. Most polymers that are commercially used are taking advantage of their polycationic character which allows not only strong ligand-DNA affinity but also competent cell penetration. Despite the relatively high transfection efficiencies, high cytotoxicity is continuously pointed out as one of the major shortcomings of polycationic polymers such as PEI. Studies on the utilization of peptides have therefore been carried out recently to overcome these problems. For these reasons, the human transcription factor Hph-1, which is currently known as a protein transduction domain (PTD), was investigated in this study to evaluate its potential as a gene delivery carrier. Although its transfection efficiency was about 10-fold lower than PEI, it displayed almost no cytotoxicity even at concentrations as high as $100{\mu}M$. Hph-1 was oxidatively polymerized to yield poly-Hph-1. The cell viability of poly-Hph-1 transfected U87MG and NIH-3T3 cells was almost as high as the control (untreated) groups, and the transfection efficiency was about 10-fold higher than PEI. This study serves as a preliminary evaluation of Hph-1 and encourages further investigation.

키워드

참고문헌

  1. Sheridan, C. Nat. Biotechnol. 2011, 29, 121. https://doi.org/10.1038/nbt.1769
  2. Boussif, O.; Lezoualch, F.; Zanta, M. A.; Mergny, M. D.; Scherman, D.; Demeneix, B.; Behr, J. P. Proc. Nat. Acad. Sci. USA 1995, 92, 7297. https://doi.org/10.1073/pnas.92.16.7297
  3. Choi, J. S.; Nam, K.; Park, J. Y.; Kim, J. B.; Lee, J. K.; Park, J. S. J. Control Release 2004, 99, 445. https://doi.org/10.1016/j.jconrel.2004.07.027
  4. An, S.; Nam, K.; Choi, S.; Bai, C. Z.; Lee, Y.; Park, J. International Journal of Nanomedicine 2013, 8, 821.
  5. Plank, C.; Tang, M. X.; Wolfe, A. R.; Szoka, F. C. Hum. Gene. Ther. 1999, 10, 319. https://doi.org/10.1089/10430349950019101
  6. Hyndman, L.; Lemoine, J. L.; Huang, L.; Porteous, D. J.; Boyd, A. C.; Nan, X. S. J. Control Release 2004, 99, 435. https://doi.org/10.1016/j.jconrel.2004.07.023
  7. Manickam, D. S.; Bisht, H. S.; Wan, L.; Mao, G. Z.; Oupicky, D. J. Control Release 2005, 102, 293. https://doi.org/10.1016/j.jconrel.2004.09.018
  8. Choi, J. M.; Kim, S. H.; Shin, J. H.; Gibson, T.; Yoon, B. S.; Lee, D. H.; Lee, S. K.; Bothwell, A. L. M.; Lim, J. S.; Lee, S. K. Proc. Nat. Acad. Sci. USA 2008, 105, 19875. https://doi.org/10.1073/pnas.0805198105
  9. Jun, X. Y.; B. F.; Xu J.; Zhang, Y. H.; Cheng, N. L.; Niu, B.; Hu, X. N.; Xiang Q.; Zhang, Z. G. Hepatobiliary & Pancreatic Diseases International 2005, 4, 4.
  10. Choi, J. M.; Ahn, M. H.; Chae, W. J.; Jung, Y. G.; Park, J. C.; Song, H. M.; Kim, Y. E.; Shin, J. A.; Park, C. S.; Park, J. W.; Park, T. K.; Lee, J. H.; Seo, B. F.; Kim, K. D.; Kim, E. S.; Lee, D. H.; Lee, S. K.; Lee, S. K. Nat. Med. 2006, 12, 574. https://doi.org/10.1038/nm1385
  11. Kim, E. S.; Yang, S. W.; Hong, D. K.; Kim, W. T.; Kim, H. G.; Lee, S. K. Biochem. Bioph. Res. Co. 2010, 392, 9. https://doi.org/10.1016/j.bbrc.2009.12.135
  12. Lee, M. J.; Cho, S. S.; You, J. R.; Lee, Y.; Kang, B. D.; Choi, J. S.; Park, J. W.; Suh, Y. L.; Kim, J. A.; Kim, D. K.; Park, J. S. Gene. Ther. 2002, 9, 859. https://doi.org/10.1038/sj.gt.3301704
  13. Oupicky, D.; Parker, A. L.; Seymour, L. W. J. Am. Chem. Soc. 2002, 124, 8. https://doi.org/10.1021/ja016440n
  14. Ng, Q. K. T.; Sutton, M. K.; Soonsawad, P.; Xing, L.; Cheng, H.; Segura, T. Mol. Ther. 2009, 17, 828. https://doi.org/10.1038/mt.2009.11
  15. Kiselev, A.; Egorova, A.; Laukkanen, A.; Baranov, V.; Urtti, A. Int. J. Pharm. 2013, 441, 736. https://doi.org/10.1016/j.ijpharm.2012.10.020
  16. Jones, D. T.; Taylor, W. R.; Thorton, J. M. Biochemistry-Us 1994, 33, 3038. https://doi.org/10.1021/bi00176a037
  17. Saier, M. H.; Yen, M. R.; Noto, K.; Tamang, D. G.; Elkan, C. Nucleic. Acids Res. 2009, 37, D274. https://doi.org/10.1093/nar/gkn862
  18. Li, W. J.; Nicol, F.; Szoka, F. C. Adv. Drug Deliver Rev. 2004, 56, 967. https://doi.org/10.1016/j.addr.2003.10.041
  19. Moghimi, S. M.; Symonds, P.; Murray, J. C.; Hunter, A. C.; Debska, G.; Szewczyk, A. Mol. Ther. 2005, 11, 990. https://doi.org/10.1016/j.ymthe.2005.02.010
  20. Lv, H. T.; Zhang, S. B.; Wang, B.; Cui, S. H.; Yan, J. J. Control Release 2006, 114, 100. https://doi.org/10.1016/j.jconrel.2006.04.014
  21. Fischer, D.; Li, Y. X.; Ahlemeyer, B.; Krieglstein, J.; Kissel, T. Biomaterials 2003, 24, 1121. https://doi.org/10.1016/S0142-9612(02)00445-3