화학공학소재연구정보센터
Macromolecular Research, Vol.11, No.1, 19-24, February, 2003
Biodistribution and Hemolysis Study of Terplex Gene Delivery System in Mice
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Polymeric gene delivery system attracts profound attention as it shows less toxicity, versatility, and reasonable gene expression efficiency. Terplex system, a synthetic biopolymeric gene delivery system consisting of stearyl poly-L-lysine (stearyl-PLL) and low density lipoprotein (LDL) was evaluated for its body distribution of gene expression of exogenously administered pDNA after tail-vein injection in mice. Kidney and spleen are two major organs with highest gene expression, whereas liver and heart showed marginal gene expression among the organs examined. Hemolytic effect of the terplex system was evaluated using human red blood cells, where terplex system did not cause significant hemolysis at the concentrations above the experimental ranges, although unmodified PLL or stearyl-PLL without LDL did. Serum stability of terplex system against enzymatic degradation was also significantly enhanced, presumably due to the steric stabilization from the polymers. Based on these findings and along with its high in vitro transfection efficiency, terplex system could serve as a safe and efficient polymeric gene delivery system with many applications for the in vivo gene therapy.
  1. Nakanishim M, Crit. Rev. Ther. Drug Carr. Syst., 12, 263 (1995)
  2. Felgner P, Adv. Drug Deliv. Rev., 5, 807 (1990)
  3. Temin H, Hum. Gene Ther., 1, 111 (1990)
  4. Kabanov A, Kabanov V, Bioconjug. Chem., 6, 7 (1995) 
  5. Miller H, Science, 287, 591 (2000) 
  6. Liand S, huang L, Gene Ther., 7, 31 (2000) 
  7. Felgner P, Gadek T, Holm M, Toman R, Chan H, Wenz M, Northrop J, Ringold M, Danielsen M, Proc. Natl. Acad. Sci. U.S.A., 21, 7413 (1987) 
  8. Schwartz B, Benoist C, Abdallah B, Scherman D, Behr J, Demeneix B, Hum. Gene Therm., 12, 1515 (1995)
  9. Felgner J, Kumar R, Sridhar C, Wheeler C, Tsai Y, Border R, Ramsey P, Martin M, Felgner P, J. Biol. Chem., 269, 2550 (1994)
  10. McLanchalan R, Biochemistry, 11, 9 (1994) 
  11. Gao X, Huang L, Biochem. Biophys. Res. Commun., 179, 280 (1991) 
  12. Kim C, Koo BW, Lee SB, Song CK, Macromol. Res., 10(3), 178 (2002)
  13. Sung YK, Yoo MK, Cho CS, Korea Polym. J., 8(1), 26 (2000)
  14. WuG, Wu C, J. Biol. Chem., 263, 14621 (1998)
  15. Abdallah B, Hassan A, Benoist C, Goula D, Behr J, Demeneix B, Hum. Gene Ther., 16, 1947 (1996)
  16. Qin L, Pahud D, Ding Y, Bielinska A, Kukowska-Latallo J, Baker J, Bromberg J, Hum. Gene Ther., 9, 553 (1998)
  17. Kim J, Maruyama A, Akaike T, Kim S, J. Control. Release, 47, 51 (1997) 
  18. Affleck D, yuL, BullD, Bailey S, Kim S, Gene Ther., 8, 349 (2001) 
  19. Kim J, Maruyama A, Akike T, Kim S, J. Control. Release, 53, 175 (1998) 
  20. Lee M, Han S, Koh K, Kim S, J. Control. Release, 74, 421 (2001)
  21. Nevo A, Vries A, Katchalsky A, Biochim. Biophys. Acta, 17, 536 (1995) 
  22. Katchalsky A, Danaon D, Nevo A, Biochim. Biophys. Acta, 33, 120 (1995) 
  23. Yu L, Suh H, Koh J, Kim S, Pharm. Res., 18, 1277 (2001)