Research Projects

MRNA-based therapeutics have applications in various diseases, including cancer and infectious diseases. However, their development faces challenges such as instability, immunogenicity, hydrophilicity, anionic charge, and large size. Non-viral vectors offer advantages over viral vectors in terms of low immunogenicity, structure, chemical versatility, and structural modification. The ideal non-viral carrier should effectively complex mRNA, protect it from degradation, enable uptake, undergo endosomal escape, and decomplex in the cytoplasm to release it for translation. Both polymeric and lipidic systems have been used for mRNA delivery, but each has limitations such as instability, limited payload capacity, and limited transfection and toxicity. Newer hybrid materials with improved key aspects are needed. The proposed project aims to develop and optimize compositions containing functionalized lipids and polymers to obtain a hybrid system (fLPH) with varying degrees of protonation and hydrophobicity/hydrophilicity for delivering mRNA-therapeutics in vivo. A lipid-polymer hybrid non-viral system consisting of cationic lipid components, endosomal escape components, hydrophilic interaction components, and amphiphilic polymer components will be used to efficiently deliver mRNA in vivo. The project will synthesize functionalized cholesterol-containing varying groups using amidation coupling chemistry, and the hybrid systems will be optimized and complexed with GFP-mRNA. Successful completion of this project will pave the way for the development of indigenous novel formulations for mRNA therapeutics, including mRNA-based vaccines, with a significant societal impact.