LNP-delivered mRNA for UGT1A1 replacement in Crigler-Najjar syndrome type 1 patients


This case study uses Applied BioMath Assess to establish the feasibility and dose projections for an mRNA enzyme replacement therapy that produces liver-specific protein glucuronosyltransferase family 1 member A1 (UGT1A1), an enzyme needed to clear bilirubin. Such therapies often need to be chronically administered to maintain efficacious outcome. As a result, the identification of feasible dose and dosing regimen is critical to establishing the feasibility of this therapeutic approach.

Using a semi-mechanistic model of an mRNA therapy in Applied BioMath Assess, we determined the dose amounts and frequencies that could sustain reductions in bilirubin levels over time. Less frequent dosing frequencies are preferred for convenience. Additionally, we investigated which design variables most strongly influence the dose level and frequency to help prioritize optimization efforts.


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