Histidylated oligolysines increase the transmembrane passage and the biological activity of antisense oligonucleotides
- 15 January 2000
- journal article
- Published by Oxford University Press (OUP) in Nucleic Acids Research
- Vol. 28 (2) , 504-512
- https://doi.org/10.1093/nar/28.2.504
Abstract
We have designed histidylated oligolysines which increase the uptake, the cytosolic delivery and the nuclear accumulation of antisense oligonucleotides (ODN). Flow cytometry analysis showed a 10-fold enhancement of the ODN uptake in the presence of histidylated oligolysines. The intracellular localizations of fluorescein-labeled ODN and of rhodamine-labeled histidylated oligolysines were investigated by confocal microscopy. Histidylated oligolysines favor the cyto-solic delivery of ODN from endosomes and increase their nuclear accumulation. In contrast, in their absence fluorescent ODN were not observed inside the nucleus but were distributed overwhelmingly within the vesicles in the cytosol. In addition, histidylated oligolysines yielded a more than 20-fold enhancement of the biological activity of antisense ODN towards the inhibition of transient as well as constitutive gene expression. Prevention of endosome lumen acidification using bafilomycin A(1)abolished the effect of histidylated oligolysines, suggesting that protonation of the histidyl residues was involved in the transmembrane passage of ODN.Keywords
This publication has 35 references indexed in Scilit:
- Efficient Gene Transfer by Histidylated Polylysine/pDNA ComplexesBioconjugate Chemistry, 1999
- Membrane Permeabilization and Efficient Gene Transfer by a Peptide Containing Several HistidinesBioconjugate Chemistry, 1998
- Cytosolic and Nuclear Delivery of Oligonucleotides Mediated by an Amphiphilic Anionic PeptideAntisense and Nucleic Acid Drug Development, 1997
- pH-sensitive, cationic liposomes: A new synthetic virus-like vectorNature Biotechnology, 1996
- Muramyl dipeptide bound to poly-l-lysine substituted with mannose and gluconoyl residues as macrophage activatorsGlycoconjugate Journal, 1989
- Quantitation of the binding, uptake, and degradation of fluoresceinylated neoglycoproteins by flow cytometryCytometry, 1987
- Polyhistidine mediates an acid-dependent fusion of negatively charged liposomesBiochemistry, 1984
- Uptake of neoglycoproteins via membrane lectin(s) of L1210 cells evidenced by quantitative flow cytofluorometry and drug targetingBiology of the Cell, 1984
- Weak bases and ionophores rapidly and reversibly raise the pH of endocytic vesicles in cultured mouse fibroblasts.The Journal of cell biology, 1982
- In situ detection of mycoplasma contamination in cell cultures by fluorescent Hoechst 33258 stainExperimental Cell Research, 1977