Combinatorial Approach Towards Development of Multifunctional Gene Transfection Vector

In the context of therapeutic applications, delivery of nucleic acids has drawn a lot of attention in the scientific community. To date, most of the gene delivery therapeutics in clinical trials are based on viral vectors, but safety issues and manufacturing costs are the major concerns of this approach. On the other hand, synthetic vectors offer greater flexibility, more facile manufacturing and safer delivery platform. Cationic lipids are one of the most well studied families in the synthetic vector based gene delivery approach. Synthetic difficulties of those lipids introduced limitations in the possibility of fast structural optimization for an efficient transfection vector. Currently, lipid-like materials, called “lipidoids”, are synthesized using very simple synthetic technique for gene delivery applications. But their transfection efficiencies are still less than that of the viral based delivery systems. So, it is necessary to search for synthetic vectors with high transfection efficiency. Ease of synthesis and opportunity for high-throughput screening of libraries of compounds motivated us designing and synthesizing lipidoids using combinatorial synthetic approach. This can produce large quantities of structure-activity data which will significantly increase the probability of finding a potential candidate for efficient gene delivery. Notably, strong electrostatic interaction between negatively charged RNA or DNA and the carrier brings limitation in the ability of most of the carriers to release the genes inside the cells. Therefore, to increase the therapeutic potential of lipid based systems, we are interested to synthesize new materials with stimuli responsive behavior and we are hypothesizing that stimuli sensitivity of the lipidoids might increase the capability of releasing the nucleic acids in response to distinct intracellular environment, thus improving transfection efficiencies.