i-ERT: Intracellular Enzyme Replacement Therapy


Intracellular enzyme replacement therapy (i-ERT) allows for the delivery of normal copies of the mRNA that make the missing or deficient enzyme inside the liver cell, or hepatocyte, thereby reinstating the normal physiology and correcting the disease.

In contrast, traditional enzyme replacement therapy (ERT) is a medical treatment that involves replacing a missing or deficient enzyme in a patient, usually through an intravenous infusion containing the enzyme. This approach does not work for many inherited orphan liver diseases because the missing enzyme is found inside the cell and the administered enzyme is unable to get inside the target cell where it is needed to be therapeutically active.

1 – Formulate therapeutic mRNA and administer to patient
2 – Uptake of therapeutic mRNA/polymer in liver
3 – Synthesize therapeutic protein inside cell

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A key challenge with mRNA therapeutics historically has been their satisfactory delivery into the patients’ cells.

This i-ERT is enabled by the PhaseRx proprietary Hybrid mRNA TechnologyTM platform, which allows synthesis of the missing enzyme inside the cell.

i-ERT Market Potential

We are not aware of any other enzyme replacement therapies for intracellular enzyme deficiencies currently being marketed for inherited enzyme deficiencies in the liver, and believe that the commercial potential for i-ERT is completely untapped and similar to the large and growing $4 billion worldwide market for conventional ERT, which includes drugs such as Cerezyme. To our knowledge, there are no ERT products on the market to treat urea cycle disorders, because the urea cycle reaction occurs inside the cell and is inaccessible to the administered enzyme. In contrast, we expect delivery of the missing enzyme using i-ERT with our Hybrid mRNA Technology to be a promising approach to treat these patients.