Skip to main content
PMC home page
Biochemical Journal logoLink to Biochemical Journal
. 1999 Jun 1;340(Pt 2):393–396.

Cationic liposome-encapsulated antisense oligonucleotide mediates efficient killing of intracellular Leishmania.

R Chakraborty 1, D Dasgupta 1, S Adhya 1, M K Basu 1
PMCID: PMC1220262  PMID: 10333480

Abstract

Antisense oligonucleotides have been considered as inhibitors of growth of intracellular parasites such as Leishmania, but only limited inhibition has been observed in vitro. We have encapsulated an antisense oligonucleotide, complementary to the Leishmania universal miniexon sequence, in cationic liposomes. Low concentrations (4 microM) of encapsulated oligonucleotides specifically reduced the amastigote burden within cultured macrophages by 80%. This result illustrates the importance of effective delivery for efficient antiparasitic activity of antisense oligonucleotides.

Full Text

The Full Text of this article is available as a PDF (86.2 KB).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Banerjee G., Medda S., Basu M. K. A novel peptide-grafted liposomal delivery system targeted to macrophages. Antimicrob Agents Chemother. 1998 Feb;42(2):348–351. doi: 10.1128/aac.42.2.348. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Banerjee G., Nandi G., Mahato S. B., Pakrashi A., Basu M. K. Drug delivery system: targeting of pentamidines to specific sites using sugar grafted liposomes. J Antimicrob Chemother. 1996 Jul;38(1):145–150. doi: 10.1093/jac/38.1.145. [DOI] [PubMed] [Google Scholar]
  3. Basu M. K. Liposomes in drug targeting. Biotechnol Genet Eng Rev. 1994;12:383–408. doi: 10.1080/02648725.1994.10647917. [DOI] [PubMed] [Google Scholar]
  4. Bennett C. F., Mirejovsky D., Crooke R. M., Tsai Y. J., Felgner J., Sridhar C. N., Wheeler C. J., Felgner P. L. Structural requirements for cationic lipid mediated phosphorothioate oligonucleotides delivery to cells in culture. J Drug Target. 1998;5(3):149–162. doi: 10.3109/10611869808995870. [DOI] [PubMed] [Google Scholar]
  5. Cazenave C., Chevrier M., Nguyen T. T., Hélène C. Rate of degradation of [alpha]- and [beta]-oligodeoxynucleotides in Xenopus oocytes. Implications for anti-messenger strategies. Nucleic Acids Res. 1987 Dec 23;15(24):10507–10521. doi: 10.1093/nar/15.24.10507. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Chakraborty P., Basu M. K. Leishmania phagolysosome: drug trafficking and protein sorting across the compartment. Crit Rev Microbiol. 1997;23(3):253–268. doi: 10.3109/10408419709115139. [DOI] [PubMed] [Google Scholar]
  7. Chaudhuri G. Scavenger receptor-mediated delivery of antisense mini-exon phosphorothioate oligonucleotide to Leishmania-infected macrophages. Selective and efficient elimination of the parasite. Biochem Pharmacol. 1997 Feb 7;53(3):385–391. doi: 10.1016/s0006-2952(96)00763-0. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Cybulsky M. I., Fries J. W., Williams A. J., Sultan P., Eddy R., Byers M., Shows T., Gimbrone M. A., Jr, Collins T. Gene structure, chromosomal location, and basis for alternative mRNA splicing of the human VCAM1 gene. Proc Natl Acad Sci U S A. 1991 Sep 1;88(17):7859–7863. doi: 10.1073/pnas.88.17.7859. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Felgner P. L., Gadek T. R., Holm M., Roman R., Chan H. W., Wenz M., Northrop J. P., Ringold G. M., Danielsen M. Lipofection: a highly efficient, lipid-mediated DNA-transfection procedure. Proc Natl Acad Sci U S A. 1987 Nov;84(21):7413–7417. doi: 10.1073/pnas.84.21.7413. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Miller S. I., Landfear S. M., Wirth D. F. Cloning and characterization of a Leishmania gene encoding a RNA spliced leader sequence. Nucleic Acids Res. 1986 Sep 25;14(18):7341–7360. doi: 10.1093/nar/14.18.7341. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Pinnaduwage P., Schmitt L., Huang L. Use of a quaternary ammonium detergent in liposome mediated DNA transfection of mouse L-cells. Biochim Biophys Acta. 1989 Oct 2;985(1):33–37. doi: 10.1016/0005-2736(89)90099-0. [DOI] [PubMed] [Google Scholar]
  12. Ramazeilles C., Mishra R. K., Moreau S., Pascolo E., Toulmé J. J. Antisense phosphorothioate oligonucleotides: selective killing of the intracellular parasite Leishmania amazonensis. Proc Natl Acad Sci U S A. 1994 Aug 16;91(17):7859–7863. doi: 10.1073/pnas.91.17.7859. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Stein C. A., Cheng Y. C. Antisense oligonucleotides as therapeutic agents--is the bullet really magical? Science. 1993 Aug 20;261(5124):1004–1012. doi: 10.1126/science.8351515. [DOI] [PubMed] [Google Scholar]
  14. Verspieren P., Cornelissen A. W., Thuong N. T., Hélène C., Toulmé J. J. An acridine-linked oligodeoxynucleotide targeted to the common 5' end of trypanosome mRNAs kills cultured parasites. Gene. 1987;61(3):307–315. doi: 10.1016/0378-1119(87)90194-6. [DOI] [PubMed] [Google Scholar]
  15. Walker I., Irwin W. J., Akhtar S. Improved cellular delivery of antisense oligonucleotides using transferrin receptor antibody-oligonucleotide conjugates. Pharm Res. 1995 Oct;12(10):1548–1553. doi: 10.1023/a:1016260110049. [DOI] [PubMed] [Google Scholar]
  16. Wang S., Lee R. J., Cauchon G., Gorenstein D. G., Low P. S. Delivery of antisense oligodeoxyribonucleotides against the human epidermal growth factor receptor into cultured KB cells with liposomes conjugated to folate via polyethylene glycol. Proc Natl Acad Sci U S A. 1995 Apr 11;92(8):3318–3322. doi: 10.1073/pnas.92.8.3318. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Wielbo D., Shi N., Sernia C. Antisense inhibition of angiotensinogen in hepatoma cell culture is enhanced by cationic liposome delivery. Biochem Biophys Res Commun. 1997 Mar 27;232(3):794–799. doi: 10.1006/bbrc.1997.6329. [DOI] [PubMed] [Google Scholar]
  18. Zelphati O., Imbach J. L., Signoret N., Zon G., Rayner B., Leserman L. Antisense oligonucleotides in solution or encapsulated in immunoliposomes inhibit replication of HIV-1 by several different mechanisms. Nucleic Acids Res. 1994 Oct 11;22(20):4307–4314. doi: 10.1093/nar/22.20.4307. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Zelphati O., Szoka F. C., Jr Mechanism of oligonucleotide release from cationic liposomes. Proc Natl Acad Sci U S A. 1996 Oct 15;93(21):11493–11498. doi: 10.1073/pnas.93.21.11493. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from Biochemical Journal are provided here courtesy of The Biochemical Society

RESOURCES