Engineered Macromolecular and Nanostructured Materials for Biomedical Relevance

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Gene therapy has drawn significant attention over the past two decades for the treatment of inherited and acquired diseases. Despite the considerable interest in gene therapy, delivery of genes to the target cells remains a huge challenge. Major research efforts are currently focused on designing suitable carrier vectors that compact and protect oligonucleotides for gene therapy. DNA or RNA is large, hydrophilic, negatively charged macromolecule, very unstable in the physiological environment and does not cross biological membranes effectively. Since both the genes and cell surfaces are negatively charged, spontaneous entry of unprotected genes inside cells is difficult. Research was initially focused on viruses as these vectors exhibited high efficiency at delivering both DNA and RNA to numerous cell lines. However, several problems associated with viral vector systems, such as toxicity, immunogenicity and limitations with respect to scale-up procedures encouraged the exploration of other potential DNA or RNA carriers into targeted tissue. Non-viral vector systems are other means for compacting DNA for systemic delivery, but, unlike viral analogues, non-viral gene carriers consistently demonstrate significant reduced transfection efficiency due to numerous extra- and intracellular obstacles. Their biocompatibility and facilitated production make them potentially useful and attractive for gene therapy. As carbohydrates are prominent on cell surfaces, they are involved in a number of cellular processes and modulate many cellular interactions. Therefore, it is not unreasonable to develop carbohydrate-based nano-systems for gene therapy since diligent engineering of these materials can transform them into highly innovative therapeutics. We have established the reversible addition-fragmentation chain transfer process (RAFT) for designing well-defined polymers mainly based on the ease of synthesizing water-soluble polymers. The RAFT process has enabled us to design and fabricate advanced cationic glycopolymers and nanogels with low toxicity for DNA/siRNA delivery. This remarkable control on the design of biomaterials has had significant impact on both their physicochemical and biological properties. Our motivation in this research program is towards the evaluation of novel carbohydrate-based macro/nano-structures for the delivery of genes in vitro. Those carbohydrate vector systems will be essentially galactose based polymers and nanogels with biologically relevant motifs for targeted and safe delivery.