Vutrisiran (ALN-TTRsc02) is an investigational, liver-directed small interfering RNA compound designed to selectively silence transthyretin gene expression, Vutrisiran is extensively used in research on transthyretin-mediated amyloidosis to evaluate RNA interference–based therapeutic strategies, disease-modifying mechanisms, and long-term suppression of pathogenic protein production.

Vutrisiran (formerly ALN-TTRSC02) is being developed as a second-generation RNAi therapeutic for treating ATTR amyloidosis. It features an siRNA designed to target a common sequence in the TTR mRNA, relevant to both wild-type and all known TTR variants. Incorporating enhanced stabilization chemistry (ESC), and attached to a triantennary GalNAc ligand, Vutrisiran aims to facilitate less frequent, subcutaneous (SC) administration[1].

Pharmacodynamic studies were conducted in non-human primates to evaluate the potency and durability of Vutrisiran. A single subcutaneous (SC) injection was administered at varying dosages. A dose of 1 mg/kg achieved a mean maximum reduction (nadir) of serum transthyretin (TTR) by 96%, with significant suppression persisting for more than 4 months. A lower dose of 0.3 mg/kg resulted in a 55% reduction. In separate repeat-dose studies, monthly administration of 1 or 3 mg/kg maintained TTR reduction at 96% relative to baseline [1].

H2O: 16 mg/mL, Sonication is recommended.