There are 2 components of the TheraPlas system: a plasmid DNA (pDNA) or an mRNA payload encoding a therapeutic protein or peptide, and a delivery system. Based on a chemically modified low-molecular-weight polymer, the delivery system is designed to protect the DNA/RNA from degradation and promote trafficking into cells and through intracellular compartments. Biocompatibility of the polymers reduces the risk of adverse immune reactions, allowing for repeat administration. Compared to naked DNA or cationic lipids, TheraPlas is generally safer, more efficient, and more cost effective.
The design of the TheraPlas delivery system is based on molecular functionalization of polyethyleneimine (PEI), a cationic delivery polymer with a distinct ability to escape from the endosomes, due to heavy protonation at acidic pH. The transfection activity and toxicity of PEI is tightly coupled to its molecular weight, heretofore limiting its clinical application. We have used molecular functionalization strategies to improve the activity of low-molecular-weight PEIs without augmenting their cytotoxicity
Another approach to improve PEI activity involves crosslinking low-molecular-weight PEIs through degradable linkages, to create larger and degradable structures. Two cross-linked polymers have been synthesized with this approach and optimized for transfection activity. Both cross-linked polymers expressed several-fold higher transfection activity than their respective monomers and lower cytotoxicity than a commercially available 25kDa polymer.