Peptide Based Intracellular Delivery

The ability to access intracellular targets is of vital importance, especially as the number of druggable intracellular targets being identified increases greatly every year. Intracellular delivery poses a formidable barrier, as many potential therapeutics are impermeable to cell membranes hindering their practical application in medicinal development. Our research seeks to approach this problem using two unique peptide based approaches capable of improving on current peptide based intracellular delivery technologies. Our first approach is to functionalize oligomeric versions of an existing HIV-TAT peptide transduction domain capable of orthogonal cargo attachment. The second approach is the de novo generation of a new class of unnatural peptides based on a neuraminic acid scaffold amenable to traditional Fmoc based solid phase peptide synthesis with expected tunable secondary structures and enhanced biostability. Both approaches afford adaptability to expected potential problems and pose an exciting addition to the toolset for use in delivering cargos to increasingly important intracellular targets.