Dendrimers and dendrons for siRNA binding: computational insights

Short double-stranded RNAs, known as short interfering RNA (siRNA), can be used to specifically down-regulate the expression of targeted genes in a process known as RNA interference (RNAi). However, the success of gene-silencing applications based on the use of synthetic siRNA critically depends on efficient intracellular delivery. In recent years, particular attention has been paid to the use of dendritic scaffolds, in particular dendrimers and dendrons, which are hyper-branched polymers characterized by a well-defined structure and whose surface can be functionalized in many different ways. These structures serve as a base to construct efficient siRNA as well as DNA nanocarriers. In fact, their multivalent character allows the creation of multiple binding sites between the positively charged groups that decorate the surface of cationic dendrons and dendrimers and the negatively charged phosphate groups present on the strands of siRNA and DNA. Despite their great number of potential applications, few attempts have been made so far to study in detail the molecular mechanism underlying the complexation process between these dendritic structures and siRNAs, and the engineering of “ideal dendritic candidates” to deliver and release genetic materials into cells still remains a non-trivial task. In this context, molecular simulation represents a “virtual bridge” between experimental approaches and theoretical models, providing a microscopic view of the molecular requirements of the interaction of RNA-based therapeutics and dendrimers.