The use of antisense oligonucleotides as putative therapeutic agents is limited by their poor delivery into the cytosol and/or the nucleus because they are not able to efficiently cross lipid bilayers. To circumvent this pitfall, anionic amphipathic peptides derived from the influenza virus fusogenic peptide have been used to destabilize membranes in an acidic environment. In this paper, we compare the ability of a monomeric and a dimeric peptide to introduce oligonucleotides into the cytosol and nuclei of several types of cultured cells. Cells incubated at pH6.2 or at a slightly lower pH in the presence of the monomeric peptide but not the dimeric peptide were efficiently permeabilized. The location of fluorescent derivatives of peptides and of oligonucleotides was assessed by confocal microscopy. Both the peptides and oligonucleotides remained entrapped in vesicular compartments at neutral pH; at acidic pH, oligonucleotides in the presence of the monomeric peptide were mainly in the nucleus, while in the presence of the dimeric peptide they co-localized with the peptide into vesicles. The data are interpreted on the basis of the spectroscopic behaviour of monomeric and dimeric peptides in relation to the environmental pH.
Skip Nav Destination
Article navigation
March 2001
-
Cover Image
Cover Image
- PDF Icon PDF LinkTable of Contents
Research Article|
March 08 2001
Delivery of oligonucleotides into mammalian cells by anionic peptides: comparison between monomeric and dimeric peptides
Isabelle FREULON;
Isabelle FREULON
1
1Centre de Biophysique Moléculaire, CNRS and Université d'Orléans, UPR 4301, Glycobiologie, Vectorologie et trafic intracellulaire, Rue Charles Sadron, F-45071 Orléans Cedex 2, France
2To whom correspondence should be addressed (e-mail mayer@cnrs-orleans.fr).
Search for other works by this author on:
Annie-Claude ROCHE;
Annie-Claude ROCHE
1Centre de Biophysique Moléculaire, CNRS and Université d'Orléans, UPR 4301, Glycobiologie, Vectorologie et trafic intracellulaire, Rue Charles Sadron, F-45071 Orléans Cedex 2, France
Search for other works by this author on:
Michel MONSIGNY;
Michel MONSIGNY
1Centre de Biophysique Moléculaire, CNRS and Université d'Orléans, UPR 4301, Glycobiologie, Vectorologie et trafic intracellulaire, Rue Charles Sadron, F-45071 Orléans Cedex 2, France
Search for other works by this author on:
Roger MAYER
Roger MAYER
2
1Centre de Biophysique Moléculaire, CNRS and Université d'Orléans, UPR 4301, Glycobiologie, Vectorologie et trafic intracellulaire, Rue Charles Sadron, F-45071 Orléans Cedex 2, France
Search for other works by this author on:
Publisher: Portland Press Ltd
Received:
November 23 2000
Accepted:
January 11 2001
Online ISSN: 1470-8728
Print ISSN: 0264-6021
The Biochemical Society, London © 2001
2001
Biochem J (2001) 354 (3): 671–679.
Article history
Received:
November 23 2000
Accepted:
January 11 2001
Citation
Isabelle FREULON, Annie-Claude ROCHE, Michel MONSIGNY, Roger MAYER; Delivery of oligonucleotides into mammalian cells by anionic peptides: comparison between monomeric and dimeric peptides. Biochem J 15 March 2001; 354 (3): 671–679. doi: https://doi.org/10.1042/bj3540671
Download citation file:
Sign in
Don't already have an account? Register
Sign in to your personal account
You could not be signed in. Please check your email address / username and password and try again.
Captcha Validation Error. Please try again.