Influenza is a contagious respiratory illness caused by influenza viruses. These viruses have several types (namely A, B and C), which are rapidly changing, and in severe cases can result in hospitalization or death. In India, since 2009, the influenza A H1N1 variant has caused many deaths each year and is an ongoing health concern. Vaccines are available against influenza, but are expensive and their slow production means they cannot be produced fast enough to protect against each mutation of the disease. A new type of vaccine based on nucleic acids, DNA and RNA, show promise for overcoming this problem, as they can be more rapidly produced to prevent or treat pathogens that are rapidly evolving, and have lower production costs. However, the bare DNA is prone to degradation in the body, which will limit its effect and application in the clinic. To overcome this challenge Dr. Sikder has been developed supramolecularly assembled nanoparticles for the safe delivery of nucleic acid vaccine with ultimate target to make silence H1N1 virus gene.
Further the knowledge gained has paved the way for DNA/RNA vaccines against other diseases to be developed in the future.
Overall, this proposal aims to lay the groundwork for extending the scope of nucleic acid vaccines by exploring the potential of supramolecular assemblies as a delivery vector. A series of π-amphiphiles have been synthesized to prepare supramolecularly assembled nucleic acid delivery system for the vaccination of influenza A H1N1 strain. The central π-amphiphile moiety has been functionalized with the nucleic acid strand via a redox responsive disulfide bond, and hydrophilic oligo-oxy aryl groups connected via a hydrogen bonding unit to promote self-assembly. Steric stabilization has been afforded to the surface decorated nucleic acid nanoparticles to protect from enzymatic hydrolysis in the complex biological environments, through co-assembly with an analogue π-amphiphile which has been alternatively decorated with poly(ethylene glycol) (PEG) chains. The therapeutic efficacy of the nano-assembly has been evaluated through transfection efficacy in macrophage cell lines.
