New treatment opportunities are emerging in the field of lipid-lowering therapy through gene-silencing approaches. Both antisense oligonucleotide inhibition and small interfering RNA technology aim to degrade gene mRNA transcripts to reduce protein production and plasma lipoprotein levels. Elevated levels of LDL, remnant lipoproteins, and lipoprotein(a) all cause cardiovascular disease, whereas elevated levels of triglyceride-rich lipoproteins in some patients can cause acute pancreatitis. The levels of each of these lipoproteins can be reduced using gene-silencing therapies by targeting proteins that have an important role in lipoprotein production or removal (for example, the protein products of ANGPTL3, APOB, APOC3, LPA, and PCSK9). Using this technology, plasma levels of these lipoproteins can be reduced by 50–90% with 2–12 injections per year; such dramatic reductions are likely to reduce the incidence of cardiovascular disease or acute pancreatitis in at-risk patients. The reported adverse effects of these new therapies include injection-site reactions, flu-like symptoms, and low blood platelet counts. However, newer-generation drugs are more efficiently delivered to liver cells, requiring lower drug doses, which leads to fewer adverse effects. Although these findings are promising, robust evidence of cardiovascular disease reduction and long-term safety is needed before these gene-silencing technologies can have widespread implementation. Before the availability of such evidence, these drugs might have roles in patients with unmet medical needs through orphan indications.

通过基因沉默方法在降脂治疗领域出现了新的治疗机会。反义寡核苷酸抑制和小干扰RNA技术都旨在降解基因mRNA转录本，以减少蛋白质产生和血浆脂蛋白水平。LDL，残余脂蛋白和脂蛋白（a）的水平升高都会引起心血管疾病，而某些患者中富含甘油三酸酯的脂蛋白水平升高会导致急性胰腺炎。可以使用基因沉默疗法，通过靶向在脂蛋白产生或去除中具有重要作用的蛋白（例如ANGPTL3，APOB，APOC3，LPA和PCSK9）。使用这项技术，每年注射2至12次，可以将这些脂蛋白的血浆水平降低50–90％。如此大幅度的降低可能会降低高危患者的心血管疾病或急性胰腺炎的发生率。这些新疗法的不良反应包括注射部位反应，流感样症状和血小板计数低。但是，新一代药物可以更有效地输送到肝细胞，需要较低的药物剂量，从而减少了不良反应。尽管这些发现是令人鼓舞的，但在这些基因沉默技术得以广泛实施之前，需要有强有力的证据证明可以减少心血管疾病并具有长期安全性。在获得此类证据之前，