Blom Dirk Jacobus, Marais Adrian David, Moodley Rajen, van der Merwe Nico, van Tonder Alet, Raal Frederick Johan
Department of Medicine, Division of Lipidology and Hatter Institute for Cardiovascular Research in Africa, University of Cape Town, Cape Town, South Africa.
Division of Chemical Pathology, Faculty of Health Sciences, University of Cape Town, Cape Town, South Africa.
Lipids Health Dis. 2022 Apr 23;21(1):41. doi: 10.1186/s12944-022-01649-3.
This review focuses on antisense oligonucleotides and small interfering ribonucleic acid therapies approved or under development for the management of lipid disorders. Recent advances in RNA-based therapeutics allow tissue-specific targeting improving safety. Multiple potential target proteins have been identified and RNA-based therapeutics have the potential to significantly improve outcomes for patients with or at risk for atherosclerotic cardiovascular disease. The advantages of RNA-based lipid modifying therapies include the ability to reduce the concentration of almost any target protein highly selectively, allowing for more precise control of metabolic pathways than can often be achieved with small molecule-based drugs. RNA-based lipid modifying therapies also make it possible to reduce the expression of target proteins for which there are no small molecule inhibitors. RNA-based therapies can also reduce pill burden as their administration schedule typically varies from weekly to twice yearly injections. The safety profile of most current RNA-based lipid therapies is acceptable but adverse events associated with various therapies targeting lipid pathways have included injection site reactions, inflammatory reactions, hepatic steatosis and thrombocytopenia. While the body of evidence for these therapies is expanding, clinical experience with these therapies is currently limited in duration and the results of long-term studies are eagerly awaited.
本综述聚焦于已获批准或正在研发的用于治疗脂质紊乱的反义寡核苷酸和小干扰核糖核酸疗法。基于RNA的疗法的最新进展使得组织特异性靶向成为可能，从而提高了安全性。多种潜在的靶蛋白已被确定，基于RNA的疗法有潜力显著改善患有动脉粥样硬化性心血管疾病或有患该病风险的患者的治疗效果。基于RNA的脂质修饰疗法的优势包括能够高度选择性地降低几乎任何靶蛋白的浓度，与基于小分子的药物相比，能更精确地控制代谢途径。基于RNA的脂质修饰疗法还能够降低那些没有小分子抑制剂的靶蛋白的表达。基于RNA的疗法还可以减轻服药负担，因为其给药方案通常从每周注射到每年注射两次不等。目前大多数基于RNA的脂质疗法的安全性是可以接受的，但与各种靶向脂质途径的疗法相关的不良事件包括注射部位反应、炎症反应、肝脂肪变性和血小板减少症。虽然这些疗法的证据越来越多，但目前这些疗法的临床经验在持续时间上有限，人们急切期待长期研究的结果。
