帕替司兰 (Onpattro)

概览

Patisiran is a transthyretin-directed small interfering RNA used to treat polyneuropathy of hereditary transthyretin-mediated amyloidosis.

作用机制

Patisirant is a double-stranded short interfering RNA (siRNA) targeting mRNA encoding both wild-type and mutant transthyretin . Patisiran enters the cell an is processed by the Dicer enzyme. This processing involved cleaving overhanging nucleotides on the edges of the RNA. Once processed the siRNA can bind to the RNA-induced silencing complex (RISC). RISC separates the strands of the RNA sequence. One strand is released and one remains bound. The bound strand then acts as a targeting sequence for a complimentary mRNA sequence. In this case, the bound strand of patisiran binds to the complimentary transthyretin mRNA and aligns the RISC complex with it. The transthyretin mRNA is then cleaved and rendered non-functional. One targeting sequence may be used to destroy many copies of complimentary mRNA.

适应症

适用于治疗成人遗传性转甲状腺素介导的淀粉样变性的多发性神经病，如转甲状腺素蛋白淀粉样变性多发性神经病（ATTR-PN）或转甲状腺素蛋白淀粉样变性心肌病（ATTR-CM）。ATTR疾病也属于罕见病。

• Hereditary transthyretin-mediated amyloidosis