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Strategies to decrease low-density lipoprotein (LDL) cholesterol could help treat atherosclerosis. Here, Gennemark et al . developed an antisense oligonucleotide (ASO) that can be delivered orally, is taken up by the liver, and targets PCSK9, which regulates the LDL receptor. Subcutaneous administration of the ASO showed high potency in mice overexpressing PCSK9, a liver half-life of 18 days in monkeys, and reduced circulating PCSK9 in humans. The oral formulation showed 5 to 7% liver bioavailability compared to subcutaneous administration in rats and dogs, and it reduced LDL cholesterol in healthy monkeys. Results support the potential of this ASO for PCSK9 inhibition while avoiding the need for injections. Inhibitors of proprotein convertase subtilisin/kexin type 9 (PCSK9) reduce low-density lipoprotein (LDL) cholesterol and are used for treatment of dyslipidemia. Current PCSK9 inhibitors are administered via subcutaneous injection. We present a highly potent, chemically modified PC

Taconic biosciences incAccreditation of laboratory animal care internationalIonis pharmaceuticalsAssociation for assessmentTaconic biosciencesBeckman coulterThermo fisher scientificCharles riverLaboratory animal care internationalAbbot scandinaviaHoriba medicalடகோனிக் உயிர் அறிவியல் இன்க்அங்கீகாரம் ஆஃப் ஆய்வகம் விலங்கு பராமரிப்பு சர்வதேசசங்கம் க்கு மதிப்பீடுடகோனிக் உயிர் அறிவியல்பெக்மேன் கூல்டர்