Publications by authors named "Carrie Rocca"
Article Synopsis
- Givosiran is an RNA interference therapy targeting liver mRNA, approved for treating acute hepatic porphyria, showing complete absorption and a quick elimination half-life of under 4 hours after subcutaneous administration.
- Its plasma exposure increases dose-proportionally without accumulation, and it binds to plasma proteins at a concentration-dependent level, with around 90% binding at clinically relevant doses in humans.
- The drug primarily affects the liver and is metabolized through nucleases instead of the cytochrome P450 system, with minimal renal and fecal excretion, indicating a low risk of drug-drug interactions.
The electrophoretic mobility shift assay (EMSA) was evaluated as an alternative to ultrafiltration (UF) to assess plasma protein binding (PPB) of small interfering RNAs (siRNA) and antisense oligonucleotides (ASO). EMSA analysis showed that PPB depended on siRNA and plasma concentration. Conversely, when analyzed by ultrafiltration, siRNA bound the filtration device nonspecifically and PPB remained >98% across physiologically relevant siRNA concentrations.
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