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Oligonucleotide lipoplexes : the influence of oligonucleotide composition on complexation

Meidan, V.M. and Glezer, J. and Amariglio, N. and Cohen, J.S. and Barenholz, Y. (2001) Oligonucleotide lipoplexes : the influence of oligonucleotide composition on complexation. BBA - General Subjects, 1568 (3). pp. 177-182. ISSN 0304-4165

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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.

Item type: Article
ID code: 37979
Keywords: base sequence, cationic liposome, lipoplex, oligonucleotide, fluorescence, Pharmacy and materia medica, Biochemistry, Biophysics, Molecular Biology, Medicine(all)
Subjects: Medicine > Pharmacy and materia medica
Department: Faculty of Science > Strathclyde Institute of Pharmacy and Biomedical Sciences
Related URLs:
    Depositing user: Pure Administrator
    Date Deposited: 28 Feb 2012 14:48
    Last modified: 04 Sep 2014 18:56
    URI: http://strathprints.strath.ac.uk/id/eprint/37979

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