Issue 36, 2015

Multivalent DNA recognition by self-assembled clusters: deciphering structural effects by fragments screening and evaluation as siRNA vectors

Abstract

The identification of low-molecular-weight clusters that effectively complex oligonucleotides of therapeutic interest is of great importance for applications in gene delivery. We recently reported the use of self-assembly processes based on chemoselective ligation in order to generate biomolecular clusters for the multivalent recognition of DNA. Herein, we exploit the modularity of this methodology to perform a one-pot fragments screening of scaffolds and binding groups. Structural parameters affecting DNA binding were observed and hits have been identified by fluorescence displacement and gel electrophoresis assays. Finally, we evaluated the potential of these systems for siRNA transfection. One biomolecular cluster was found to effectively complex and transport a 21-mer siRNA inside MCF7 human breast cancer cells, resulting in a significant knockdown of the target gene.

Graphical abstract: Multivalent DNA recognition by self-assembled clusters: deciphering structural effects by fragments screening and evaluation as siRNA vectors

Supplementary files

Article information

Article type
Paper
Submitted
10 Jul 2015
Accepted
31 Jul 2015
First published
06 Aug 2015

Org. Biomol. Chem., 2015,13, 9427-9438

Multivalent DNA recognition by self-assembled clusters: deciphering structural effects by fragments screening and evaluation as siRNA vectors

E. Bartolami, Y. Bessin, N. Bettache, M. Gary-Bobo, M. Garcia, P. Dumy and S. Ulrich, Org. Biomol. Chem., 2015, 13, 9427 DOI: 10.1039/C5OB01404B

To request permission to reproduce material from this article, please go to the Copyright Clearance Center request page.

If you are an author contributing to an RSC publication, you do not need to request permission provided correct acknowledgement is given.

If you are the author of this article, you do not need to request permission to reproduce figures and diagrams provided correct acknowledgement is given. If you want to reproduce the whole article in a third-party publication (excluding your thesis/dissertation for which permission is not required) please go to the Copyright Clearance Center request page.

Read more about how to correctly acknowledge RSC content.

Social activity

Spotlight

Advertisements