Cationic siRNAs Provide Carrier-Free Gene Silencing in Animal Cells

siRNA-mediated gene silencing requires intracellular delivery of the nucleic acid. We have developed a carrierless molecular approach that follows the same cell entry route as cationic supramolecular complexes, yet should avoid the extracellular barriers encountered by nanoparticles. Cationic oligospermine−oligonucleotide conjugates (ZNAs, for Zip Nucleic Acids) were synthesized stepwise on an oligonucleotide synthesizer using a DMT-spermine phosphoramidite derivative. They were shown to enter cells and have access to the cytoplasm, provided their formal charge ratio N/P was >1.5. Cationic siRNAs that fulfilled this condition were shown to achieve selective inhibition of luciferase gene expression in the submicromolar concentration range in constitutively luciferase-expressing cells

Polydiacetylenic nanofibers as new siRNA vehicles for in vitro and in vivo delivery

Polydiacetylenic nanofibers (PDA-Nfs) obtained by photopolymerization of surfactant 1 were optimized for intracellular delivery of small interfering RNAs (siRNAs). PDA-Nfs/siRNA complexes efficiently silenced the oncogene Lim-1 in the renal cancer cells 786-O in vitro. Intraperitoneal injection of PDA-Nfs/siLim1 downregulated Lim-1 in subcutaneous tumor xenografts obtained with 786-O cells in nude mice. Thus, PDA-Nfs represent an innovative system for in vivo delivery of siRNAs

Gene delivery with polycationic fullerene hexakis-adducts

Polyplexes prepared from DNA and globular compact polycationic derivatives constructed around a fullerene hexakis-adduct core have shown remarkable gene delivery capabilities