{"id":14175,"date":"2025-03-03T15:07:00","date_gmt":"2025-03-03T14:07:00","guid":{"rendered":"https:\/\/www.humangenetik-umg.de\/?p=14175"},"modified":"2025-03-03T15:07:00","modified_gmt":"2025-03-03T14:07:00","slug":"gene-of-the-month-february-pcsk9","status":"publish","type":"post","link":"https:\/\/www.humangenetik-umg.de\/en\/gene-of-the-month-february-pcsk9\/","title":{"rendered":"Gene of the Month &#8211; February: PCSK9"},"content":{"rendered":"<p>Silencing the <em>PCSK9<\/em> gene through epigenetic editing may be a novel and promising future strategy to treat hypercholesterolemia. In a study published in <em>Nature Medicine<\/em>, researchers describe the development and in vivo application of an epigenetic editor that specifically induces DNA methylation at the promotor of the <em>PCSK9<\/em> gene, effectively silencing it. Epigenetic editing involves altering or establishing epigenetic marks at targeted sites of the genome to modulate gene expression. Unlike genome editing techniques as, for example, CRISPR\/Cas9, these methods do not modify the DNA sequence.<\/p>\n<p>PCSK9 is important for regulating blood cholesterol level. This protein promotes degradation of low density lipoprotein (LDL) cholesterol receptors on the surface of liver cell, leading to an elevated concentration of cholesterol in blood. Higher blood cholesterol levels are a key risk factor for cardiovascular disease.<\/p>\n<p>The authors of the study investigated their specifically designed epigenetic editor in different models. In transgenic mice, a single administration of lipid nanoparticles carrying the editor resulted in almost complete and lasting silencing of the human <em>PCSK9<\/em> gene, which remained effective even after regeneration of liver cells. In cynomolgus monkeys, a single dose reduced circulating PCSK9 protein levels by 90% and LDL cholesterol by 70 %. Furthermore, the researchers were able to reverse the epigenetic editing using a targeted activator.<\/p>\n[vc_column_text]Tremblay F, Xiong Q, Shah SS, \u2026, Jaffe AB. A potent epigenetic editor targeting human PCSK9 for durable reduction of low-density lipoprotein cholesterol levels. <em>Nat Med.<\/em> 2025 Feb 10. doi: 10.1038\/s41591-025-03508-x. Epub ahead of print. [\/vc_column_text]\n[mk_button dimension=&#8221;flat&#8221; size=&#8221;medium&#8221; icon=&#8221;mk-icon-long-arrow-right&#8221; icon_anim=&#8221;side&#8221; url=&#8221;https:\/\/www.ncbi.nlm.nih.gov\/pubmed\/39930141&#8243; target=&#8221;_blank&#8221; bg_color=&#8221;#006699&#8243; btn_hover_bg=&#8221;#000000&#8243; btn_hover_txt_color=&#8221;#ffffff&#8221;]Article in PubMed[\/mk_button][mk_padding_divider size=&#8221;30&#8243;]\n","protected":false},"excerpt":{"rendered":"<p>Silencing the PCSK9 gene through epigenetic editing may be a novel and promising future strategy to treat hypercholesterolemia. In a study published in Nature Medicine, researchers describe the development and in vivo application of an epigenetic editor that specifically induces DNA methylation at the promotor of the PCSK9 gene, effectively silencing it. Epigenetic editing involves [&hellip;]<\/p>\n","protected":false},"author":3,"featured_media":0,"comment_status":"closed","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[54],"tags":[],"class_list":["post-14175","post","type-post","status-publish","format-standard","hentry","category-gene-of-the-month"],"yoast_head":"<!-- This site is optimized with the Yoast SEO plugin v26.8 - https:\/\/yoast.com\/product\/yoast-seo-wordpress\/ -->\n<title>Gene of the Month - February: PCSK9 - Institut f\u00fcr Humangenetik<\/title>\n<meta name=\"description\" content=\"Silencing the PCSK9 gene through epigenetic editing may be a novel and promising future strategy to treat hypercholesterolemia.\" \/>\n<meta name=\"robots\" content=\"index, follow, max-snippet:-1, max-image-preview:large, max-video-preview:-1\" \/>\n<link rel=\"canonical\" href=\"https:\/\/www.humangenetik-umg.de\/en\/gene-of-the-month-february-pcsk9\/\" \/>\n<meta property=\"og:locale\" content=\"en_US\" \/>\n<meta property=\"og:type\" content=\"article\" \/>\n<meta property=\"og:title\" content=\"Gene of the Month - February: PCSK9 - Institut f\u00fcr Humangenetik\" \/>\n<meta property=\"og:description\" content=\"Silencing the PCSK9 gene through epigenetic editing may be a novel and promising future strategy to treat hypercholesterolemia.\" \/>\n<meta property=\"og:url\" content=\"https:\/\/www.humangenetik-umg.de\/en\/gene-of-the-month-february-pcsk9\/\" \/>\n<meta property=\"og:site_name\" content=\"Institut f\u00fcr Humangenetik\" \/>\n<meta property=\"article:published_time\" content=\"2025-03-03T14:07:00+00:00\" \/>\n<meta name=\"author\" content=\"KB\" \/>\n<meta name=\"twitter:card\" content=\"summary_large_image\" \/>\n<meta name=\"twitter:label1\" content=\"Written by\" \/>\n\t<meta name=\"twitter:data1\" content=\"KB\" \/>\n\t<meta name=\"twitter:label2\" content=\"Est. reading time\" \/>\n\t<meta name=\"twitter:data2\" content=\"2 minutes\" \/>\n<script type=\"application\/ld+json\" class=\"yoast-schema-graph\">{\"@context\":\"https:\/\/schema.org\",\"@graph\":[{\"@type\":\"Article\",\"@id\":\"https:\/\/www.humangenetik-umg.de\/en\/gene-of-the-month-february-pcsk9\/#article\",\"isPartOf\":{\"@id\":\"https:\/\/www.humangenetik-umg.de\/en\/gene-of-the-month-february-pcsk9\/\"},\"author\":{\"name\":\"KB\",\"@id\":\"https:\/\/www.humangenetik-umg.de\/en\/#\/schema\/person\/521bbb2a6ceb55060a1ef5eccb794675\"},\"headline\":\"Gene of the Month &#8211; 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