Bulletin of the Korean Chemical Society

  • 제34권3호
  • /
  • Pages.735-742
  • /
  • 2013
  • /
  • 0253-2964(pISSN)
  • /
  • 1229-5949(eISSN)
대한화학회 (Korean Chemical Society)
권호 표지
DOI QR코드

DOI QR Code

Antiviral Efficacy of a Short PNA Targeting microRNA-122 Using Galactosylated Cationic Liposome as a Carrier for the Delivery of the PNA-DNA Hybrid to Hepatocytes

  • Kim, Hyoseon (Department of Bioscience and Biotechnology, Konkuk University) ;
  • Lee, Kwang Hyun (Department of Bioscience and Biotechnology, Konkuk University) ;
  • Kim, Kyung Bo (Department of Bioscience and Biotechnology, Konkuk University) ;
  • Park, Yong Serk (Department of Biomedical Laboratory Science, Yonsei University) ;
  • Kim, Keun-Sik (Department of Biomedical Laboratory Science, Konyang University) ;
  • Kim, Dong-Eun (Department of Bioscience and Biotechnology, Konkuk University)
  • 투고 : 2012.11.07
  • 심사 : 2012.12.05
  • 발행 : 2013.03.20
PDF 다운로드
⟨ 이전 논문 다음 논문 ⟩

초록

Peptide nucleic acids (PNAs) that bind to complementary nucleic acid sequences with extraordinarily high affinity and sequence specificity can be used as antisense oligonucleotides against microRNAs, namely antagomir PNAs. However, methods for efficient cellular delivery must be developed for effective use of PNAs as therapeutic agents. Here, we demonstrate that antagomir PNAs can be delivered to hepatic cells by complementary DNA oligonucleotide and cationic liposomes containing galactosylated ceramide and a novel cationic lipid, DMKE (O,O'-dimyristyl-N-lysyl glutamate), through glycoprotein-mediated endocytosis. An antagomir PNA was designed to target miR-122, which is required for translation of the hepatitis C virus (HCV) genome in hepatocytes, and was hybridized to a DNA oligonucleotide for complexation with cationic liposome. The PNA-DNA hybrid molecules were efficiently internalized into hepatic cells by complexing with the galactosylated cationic liposome in vitro. Galactosylation of liposome significantly enhanced both lipoplex cell binding and PNA delivery to the hepatic cells. After 4-h incubation with galactosylated lipoplexes, PNAs were efficiently delivered into hepatic cells and HCV genome translation was suppressed more than 70% through sequestration of miR-122 in cytoplasm. PNAs were readily released from the PNA-DNA hybrid in the low pH environment of the endosome. The present study indicates that transfection of PNA-DNA hybrid molecules using galactosylated cationic liposomes can be used as an efficient non-viral carrier for antagomir PNAs targeted to hepatocytes.

키워드

참고문헌

  1. Filipowicz, W.; Bhattacharyya, S. N.; Sonenberg, N. Nat. Rev. Genet. 2008, 9, 102.
  2. Haramati, S.; Chapnik, E.; Sztainberg, Y.; Eilam, R.; Zwang, R.; Gershoni, N.; McGlinn, E.; Heiser, P. W.; Wills, A. M.; Wirguin, I.; Rubin, L. L.; Misawa, H.; Tabin, C. J.; Brown, R., Jr.; Chen, A.; Hornstein, E. Proc. Natl. Acad. Sci. USA 2010, 107, 13111. https://doi.org/10.1073/pnas.1006151107
  3. Thum, T.; Gross, C.; Fiedler, J.; Fischer, T.; Kissler, S.; Bussen, M.; Galuppo, P.; Just, S.; Rottbauer, W.; Frantz, S.; Castoldi, M.; Soutschek, J.; Koteliansky, V.; Rosenwald, A.; Basson, M. A.; Licht, J. D.; Pena, J. T.; Rouhanifard, S. H.; Muckenthaler, M. U.; Tuschl, T.; Martin, G. R.; Bauersachs, J.; Engelhardt, S. Nature 2008, 456, 980. https://doi.org/10.1038/nature07511
  4. Garzon, R.; Marcucci, G.; Croce, C. M. Nat. Rev. Drug. Discov. 2010, 9, 775. https://doi.org/10.1038/nrd3179
  5. Lanford, R. E.; Hildebrandt-Eriksen, E. S.; Petri, A.; Persson, R.; Lindow, M.; Munk, M. E.; Kauppinen, S.; Orum, H. Science 2010, 327, 198. https://doi.org/10.1126/science.1178178
  6. Santhakumar, D.; Forster, T.; Laqtom, N. N.; Fragkoudis, R.; Dickinson, P.; Abreu-Goodger, C.; Manakov, S. A.; Choudhury, N. R.; Griffiths, S. J.; Vermeulen, A.; Enright, A. J.; Dutia, B.; Kohl, A.; Ghazal, P.; Buck, A. H. Proc. Natl. Acad. Sci. USA 2010, 107, 13830. https://doi.org/10.1073/pnas.1008861107
  7. Jopling, C. L.; Yi, M.; Lancaster, A. M.; Lemon, S. M.; Sarnow, P. Science 2005, 309, 1577. https://doi.org/10.1126/science.1113329
  8. Krutzfeldt, J.; Rajewsky, N.; Braich, R.; Rajeev, K. G.; Tuschl, T.; Manoharan, M.; Stoffel, M. Nature 2005, 438, 685. https://doi.org/10.1038/nature04303
  9. Lennox, K. A.; Behlke, M. A. Gene Ther. 2011, 18, 1111. https://doi.org/10.1038/gt.2011.100
  10. Davis, S.; Lollo, B.; Freier, S.; Esau, C. Nucleic Acids Res. 2006, 34, 2294. https://doi.org/10.1093/nar/gkl183
  11. Orom, U. A.; Kauppinen, S.; Lund, A. H. Gene 2006, 372, 137. https://doi.org/10.1016/j.gene.2005.12.031
  12. Fabani, M. M.; Gait, M. J. RNA 2008, 14, 336.
  13. Meister, G.; Landthaler, M.; Dorsett, Y.; Tuschl, T. RNA 2004, 10, 544. https://doi.org/10.1261/rna.5235104
  14. Elmen, J.; Lindow, M.; Schutz, S.; Lawrence, M.; Petri, A.; Obad, S.; Lindholm, M.; Hedtjarn, M.; Hansen, H. F.; Berger, U.; Gullans, S.; Kearney, P.; Sarnow, P.; Straarup, E. M.; Kauppinen, S. Nature 2008, 452, 896. https://doi.org/10.1038/nature06783
  15. Buchardt, O.; Egholm, M.; Berg, R. H.; Nielsen, P. E. Trends Biotechnol. 1993, 11, 384. https://doi.org/10.1016/0167-7799(93)90097-S
  16. Nielsen, P. E.; Egholm, M.; Berg, R. H.; Buchardt, O. Science 1991, 254, 1497. https://doi.org/10.1126/science.1962210
  17. Jensen, K. K.; Orum, H.; Nielsen, P. E.; Norden, B. Biochemistry 1997, 36, 5072. https://doi.org/10.1021/bi9627525
  18. Larsen, H. J.; Bentin, T.; Nielsen, P. E. Biochim. Biophys. Acta 1999, 1489, 159. https://doi.org/10.1016/S0167-4781(99)00145-1
  19. Koppelhus, U.; Nielsen, P. E. Adv. Drug. Deliv. Rev. 2003, 55, 267. https://doi.org/10.1016/S0169-409X(02)00182-5
  20. Oh, S. Y.; Ju, Y.; Kim, S.; Park, H. Oligonucleotides 2010, 20, 225. https://doi.org/10.1089/oli.2010.0238
  21. Turner, J. J.; Ivanova, G. D.; Verbeure, B.; Williams, D.; Arzumanov, A. A.; Abes, S.; Lebleu, B.; Gait, M. J. Nucleic Acids Res. 2005, 33, 6837. https://doi.org/10.1093/nar/gki991
  22. Pardridge, W. M.; Boado, R. J.; Kang, Y. S. Proc. Natl. Acad. Sci. USA 1995, 92, 5592. https://doi.org/10.1073/pnas.92.12.5592
  23. Shiraishi, T.; Hamzavi, R.; Nielsen, P. E. Nucleic Acids Res. 2008, 36, 4424. https://doi.org/10.1093/nar/gkn401
  24. Hamilton, S. E.; Simmons, C. G.; Kathiriya, I. S.; Corey, D. R. Chem. Biol. 1999, 6, 343. https://doi.org/10.1016/S1074-5521(99)80046-5
  25. Song, Y. K.; Liu, F.; Chu, S.; Liu, D. Hum Gene Ther. 1997, 8, 1585. https://doi.org/10.1089/hum.1997.8.13-1585
  26. Hofland, H. E.; Shephard, L.; Sullivan, S. M. Proc. Natl. Acad. Sci. USA 1996, 93, 7305. https://doi.org/10.1073/pnas.93.14.7305
  27. Kim, H. S.; Song, I. H.; Kim, J. C.; Kim, E. J.; Jang, D. O.; Park, Y. S. J. Control. Release 2006, 115, 234. https://doi.org/10.1016/j.jconrel.2006.08.003
  28. Kim, H. S.; Moon, J.; Kim, K. S.; Choi, M. M.; Lee, J. E.; Heo, Y.; Cho, D. H.; Jang, D. O.; Park, Y. S. Bioconjug. Chem. 2004, 15, 1095. https://doi.org/10.1021/bc049934t
  29. Kim, K. S.; Park, Y. S.; Hong, H. J.; Kim, K. P.; Lee, K. H.; Kim, D. E. Bull. Korean Chem. Soc. 2012, 33, 651. https://doi.org/10.5012/bkcs.2012.33.2.651
  30. Lee, B.; Kim, K. B.; Oh, S.; Choi, J. S.; Park, J. S.; Min, D. H.; Kim, D. E. Oligonucleotides 2010, 20, 285. https://doi.org/10.1089/oli.2010.0256
  31. Ashwell, G.; Harford, J. Annu. Rev. Biochem. 1982, 51, 531. https://doi.org/10.1146/annurev.bi.51.070182.002531
  32. Nastruzzi, C.; Cortesi, R.; Esposito, E.; Gambari, R.; Borgatti, M.; Bianchi, N.; Feriotto, G.; Mischiati, C. J. Control. Release 2000, 68, 237. https://doi.org/10.1016/S0168-3659(00)00273-X
  33. Wu, G. Y.; Wu, C. H. J. Biol. Chem. 1988, 263, 14621.
  34. Mannisto, M.; Vanderkerken, S.; Toncheva, V.; Elomaa, M.; Ruponen, M.; Schacht, E.; Urtti, A. J Control Release 2002, 83, 169. https://doi.org/10.1016/S0168-3659(02)00178-5
  35. Henke, J. I.; Goergen, D.; Zheng, J.; Song, Y.; Schuttler, C. G.; Fehr, C.; Junemann, C.; Niepmann, M. EMBO J. 2008, 27, 3300. https://doi.org/10.1038/emboj.2008.244
  36. Ishihara, T.; Kano, A.; Obara, K.; Saito, M.; Chen, X.; Park, T. G.; Akaike, T.; Maruyama, A. J. Control. Release 2011, 155, 34. https://doi.org/10.1016/j.jconrel.2010.10.014

피인용 문헌

  1. Galactosylated Liposomes for Targeted Co-Delivery of Doxorubicin/Vimentin siRNA to Hepatocellular Carcinoma vol.6, pp.8, 2016, https://doi.org/10.3390/nano6080141
  2. Synthesis of anionic peptide nucleic acid oligomers including γ-carboxyethyl thymine monomers vol.25, pp.1, 2013, https://doi.org/10.1016/j.mencom.2015.01.017
  3. From Bulk to Nanoparticles: An Overview of Antiviral Materials, Its Mechanisms, and Applications vol.38, pp.8, 2013, https://doi.org/10.1002/ppsc.202100044