The field of protein therapeutics offers significant clinical promise, but lacks a simple platform for cytosolic delivery of bioactive proteins<i>. </i>Here, we describe a generalized method for the direct delivery of therapeutic proteins in their active form into the cytosol of the cell via a biodegradable, non-immunogenic delivery platform. This is accomplished using a functionalized cationic poly oxanorbornene imide (PONI) polymer, and an engineered glutamic acid-tagged (E-tagged) variant of the protein of interest. These polymer nanocomposites fuse with the cell membrane to deliver their protein cargo directly into the cytosol, without suffering from entrapment or degradation. This system was implemented using three proteins of varying size, charge, and function to demonstrate its versatility. This wide range of potential demonstrates the feasibility of this platform for the effective, generalized delivery of therapeutic proteins.

Polymeric nanoassemblies for direct delivery of active therapeutic proteins

256th National Meeting (2018)

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