Oligonucleotide lipoplexes: The influence of oligonucleotide composition on complexation

Victor M. Meidan, Judith Glezer, Ninette Amariglio, Jack S. Cohen, Yechezkel Barenholz

Research output: Contribution to journalArticlepeer-review

19 Scopus citations

Abstract

Despite extensive investigations into oligonucleotide lipoplexes, virtually no work has addressed whether the physicochemical properties of these assemblies vary as a function of the constituent oligonucleotide (ODN) sequence and/or composition. The present study was aimed at answering this question. To this end, we complexed N-(1-(2,3-dioleoyloxy)propyl)-N,N,N-trimethylammonium chloride (DOTAP) liposomes, in dispersion, with either 18-mer phosphorothiote homo-oligonucleotides composed of either adenine, thymidine or cytosine; or one of three structurally related 18-mer phosphorothioate oligonucleotides (S-ODNs) (G3139, its reverse sequence and its two-base mismatch). After ODN addition to vesicles at different mole ratios, changes in pH and electrical surface potential at the lipid-water interface were analyzed by using the fluorophore heptadecyl-7-hydroxycoumarin while particle size distributions were analyzed by static-light scattering. The results indicate that each homo-oligonucleotide does indeed exhibit different complexation behavior. In particular, the maximal level of DOTAP neutralization by the polyadenine S-ODN is much lower than that for the two other homo-oligonucleotides and hence its lipoplex is much more positively charged. Much smaller electrostatic differences are also apparent between lipoplexes formed from each of the G3139-related ODNs. This paper identifies nucleotide base selection and sequence as a variable that can affect the physicochemical properties of oligonucleotide lipoplexes and hence probably their transfection competency.

Original languageEnglish
Pages (from-to)177-182
Number of pages6
JournalBiochimica et Biophysica Acta - General Subjects
Volume1568
Issue number3
DOIs
StatePublished - 19 Dec 2001
Externally publishedYes

Bibliographical note

Funding Information:
This study was supported in part by Israel Science Foundation Grant ISF 30/98-16.1 to J.S.C. and Y.B. We would like to thank Genta Inc. for the supplies of G3139, G3622 and G4126.

Keywords

  • 4-Heptadecyl-7-hydroxycoumarin
  • Base sequence
  • Cationic liposome
  • Fluorescence
  • Lipoplex
  • Oligonucleotide

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