Cytosolic delivery of proteins via amphiphilic oligomers

61 pagesThe discovery of the first recombinant protein Insulin has made protein therapeutics major players in detecting, preventing and curing diseases. However, small molecules are being extensively used to target intracellular components over protein therapeutics despite the large repertoire of intracellular targets for protein-based drugs. This is due to the polar and charged nature of proteins, among other factors, that make them intrinsically difficult to deliver into mammalian cells. While there are delivery techniques that aid intracellular protein transport, most systems face several challenges including endosomal trapping. Hence, there is a need for alternative delivery vehicles that can overcome the limitations of traditional delivery techniques. In this work, the potential of a new class of amphiphilic oligomers as intracellular delivery vehicles was investigated. Non-specific conjugation of Cell Penetrating Oligothioetheramides (CPOT) on super folder Green Fluorescent Protein (sfGFP) facilitated protein internalization into mammalian cells. We hypothesize that the CPOT delivery capability lies in its amphiphilic nature and the remodeling of protein surface properties. Further, the abiotic nature of CPOTs allow it to evade proteolytic degradation and deter unwanted interactions with the extracellular matrix. Ultimately, understanding the correlation between structure and intracellular delivery capability will help in the development of next generation drug delivery vehicles for macromolecules