I-Corps: Protein Transduction Domain Mimics to Revolutionize Immunology

University Of Massachusetts Amherst, Amherst MA

Investigators

Abstract

The proposed technology is based on the discovery of a class of polymeric protein transduction domain mimics (PTDMs) with the unique ability to intra-cellularly deliver a large variety of biomolecules (small molecules, nucleic acids, proteins and even whole, intact antibodies). Both in vitro and in vivo (with mouse models) experiments have been successfully performed demonstrating the efficacy of this technology. These molecules are synthesized via Ring-Opening Metathesis Polymerization (ROMP), which allows high fidelity over the chemical composition and structure. These PTDMs do not require covalent attached of the cargo, making this innovation applicable to various biomolecules and extremely easy to use. This innovation gives potential access to many intracellular compartments and functions thus offering new research and therapeutic opportunities. Accessibility to the human body and its highly regulated functions has always been one of the biggest challenges for biomedical sciences. The human genome and proteome projects have greatly contributed to elucidate many biological and molecular functions of the human body and to advance treatment of diseases by discovering new cellular targets. Unfortunately, this important knowledge cannot yet been fully applied because of the lack of permeability and the high selectivity of the cell membrane which makes these targets inaccessible. The delivery described in this proposal has the potential to enable many new research and application opportunities, especially, but not exclusively, in the immunology field where it will finally become possible to manipulate the so far impenetrable T-cells. T-cells play a critical role in cell-mediated immune response, for example against infections, cancer and HIV. The ability to control their activation, in a more efficient and safer way than the traditional electroporation and virus infection, will have a big societal and commercial impact.