title: 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.
authors.affiliation: Institut des Biomolécules Max Mousseron (IBMM), UMR 5247, CNRS, Université Montpellier, ENSCM, Ecole Nationale Supérieure de Chimie de Montpellier, 8 Rue de l'Ecole Normale, 34296 Montpellier cedex 5, France. nadir.bettache@univ-montp2.fr Sebastien.Ulrich@enscm.fr.
authors.forename: Eline
authors.initials: E
authors.lastname: Bartolami
authors.forename: Yannick
authors.initials: Y
authors.lastname: Bessin
authors.forename: Nadir
authors.initials: N
authors.lastname: Bettache
authors.forename: Magali
authors.initials: M
authors.lastname: Gary-Bobo
authors.forename: Marcel
authors.initials: M
authors.lastname: Garcia
authors.forename: Pascal
authors.initials: P
authors.lastname: Dumy
authors.forename: Sébastien
authors.initials: S
authors.lastname: Ulrich
mesh_terms: D001665:Binding Sites; D004273:DNA, Neoplasm / Q000737:chemistry* / Q000235:genetics*; D005822:Genetic Vectors / Q000737:chemistry* / Q000235:genetics*; D006801:Humans; D006835:Hydrazones / Q000138:chemical synthesis / Q000737:chemistry*; D061986:MCF-7 Cells; D015394:Molecular Structure; D034741:RNA, Small Interfering / Q000737:chemistry / Q000235:genetics*; D014162:Transfection / Q000379:methods*
chemical_list: D004273:DNA, Neoplasm; D006835:Hydrazones; D034741:RNA, Small Interfering