Interaction between single strands of siRNA and different chemical groups

Abstract

Event Abstract Back to Event Interaction between single strands of siRNA and different chemical groups Lucie Giraud1, Warren Viricel1, Jeanne Chain1 and Suzanne Giasson1, 2 1 University of Montreal, Faculty of Pharmacy, Canada 2 University of Montreal, Department of Chemistry, Canada Gene silencing activity of small interfering RNA (siRNA) has been demonstrated for double and single strands[1]. To overcome environmental degradation and sufficient dose delivery to target cells, actual strategies consist to complex siRNA using, the double strand form with cationic colloids through electrostatic interactions[2]. Unfortunately cationic vector are known to caused more toxicity than uncharged colloids. Single strand of siRNA (ss-siRNA) demonstrated similar therapeutic effects than the double strands forms but seems to offer more possibilities of complexation using various interactions as illustrated in Figure 1. To better understand the fundamental aspect driving the complexation of siRNA single strands with macromolecules or nanovectors (liposomes or polymeric nanoparticles), the interaction forces between flat surfaces of various chemistries across a siRNA solution were quantitatively investigated using the Surface Forces Apparatus. In addition, the complexation of ss-siRNA with liposomes of different surface charges was conducted in order to investigate the loading efficiency and the strength of complexation. The results show that ss-siRNA can self-assembled onto hydrophilic (positively and negatively charged) and hydrophobic surfaces suggesting that the complexation of siRNA does not only occur through electrostatic interactions but also through hydrophobic interactions and hydrogen bonding. Moreover, the binding strength and the conformation depend on the nature of the interactions between the siRNA and the surfaces. This fundamental investigation opens up new possibilities for designing nanovectors such as liposomes with controlled interactions for enhancing the efficiency in siRNA complexation and its controlled release.