title: Development of Antisense Drugs for Dyslipidemia.
abstract: 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.
authors.affiliation: Graduate School of Pharmaceutical Sciences, Osaka University.
authors.forename: Tsuyoshi
authors.initials: T
authors.lastname: Yamamoto
authors.forename: Fumito
authors.initials: F
authors.lastname: Wada
authors.forename: Mariko
authors.initials: M
authors.lastname: Harada-Shiba
mesh_terms: D015507:Drugs, Investigational / Q000627:therapeutic use*; D050171:Dyslipidemias / Q000235:genetics* / Q000628:therapy*; D015316:Genetic Therapy; D006801:Humans; D016376:Oligonucleotides, Antisense / Q000627:therapeutic use*
chemical_list: D015507:Drugs, Investigational; D016376:Oligonucleotides, Antisense