Oligonucleotide lipoplexes: the influence of oligonucleotide composition on complexation.
Biochim Biophys Acta
; 1568(3): 177-82, 2001 Dec 19.
Article
em En
| MEDLINE
| ID: mdl-11786223
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.
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Bases de dados:
MEDLINE
Assunto principal:
Tionucleotídeos
/
Oligonucleotídeos Antissenso
/
Lipossomos
Tipo de estudo:
Prognostic_studies
Idioma:
En
Revista:
Biochim Biophys Acta
Ano de publicação:
2001
Tipo de documento:
Article
País de afiliação:
Israel