PAMAM dendrimers interact with biological RNA molecules

Polycationic dendrimer-based gene transfer is one of the most important biological applications of dendrimers, which involves electrostatic interactions between the positively charged dendrimer end groups and the negatively charged phosphate groups in DNA. Such features could also be used to bind biologically important RNA molecules, which are emerging as both important therapeutic targets and therapeutic agents. With a view to using dendrimers to target RNA as well as to deliver RNA agents, we have evaluated a series of new polycationic dendrimers with different cores and different end groups for their interaction with the Candida ribozymes. The amine terminating dendrimers bind strongly to the ribozyme and efficiently inhibit the activity of the ribozyme. The inhibition effects increase with the increasing dendrimer generation, which reflects the cooperative amplification processes at work, depending on the size and three-dimensional structure of the dendrimers. The possibility of closely controlling the size, shape and surface chemistry of dendrimers gives us a unique opportunity of creating a repertoire of structure-, sizeand shape-tailored dendrimers binding to various RNA molecules as required. Our findings open new perspectives for using polycationic dendrimers for both RNA targeting and RNA delivery.