Development of Antisense Drugs for Dyslipidemia
نویسندگان
چکیده
Abnormal elevation of low-density lipoprotein (LDL) and triglyceride-rich lipoproteins in plasma as well as dysfunction of anti-atherogenic high-density lipoprotein (HDL) have both been recognized as essential components of the pathogenesis of atherosclerosis and are classified as dyslipidemia. This review describes the arc of development of antisense oligonucleotides for the treatment of dyslipidemia. Chemically-armed antisense candidates can act on various kinds of transcripts, including mRNA and miRNA, via several different endogenous antisense mechanisms, and have exhibited potent systemic anti-dyslipidemic effects. Here, we present specific cutting-edge technologies have recently been brought into antisense strategies, and describe how they have improved the potency of antisense drugs in regard to pharmacokinetics and pharmacodynamics. In addition, we discuss perspectives for the use of armed antisense oligonucleotides as new clinical options for dyslipidemia, in the light of outcomes of recent clinical trials and safety concerns indicated by several clinical and preclinical studies.
منابع مشابه
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Circulating lipoproteins containing cholesterol and triglycerides are major risk factors for many cardiovascular diseases (CVD). Many therapeutic strategies targeting lipid metabolism have been successfully used to treat dyslipidemia and subsequently reduce cardiovascular risk. Most notably, statins, which effectively lower low-density lipoprotein-cholesterol (LDL-C), have been widely used and ...
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