{"id":44392,"date":"2014-07-31T18:15:18","date_gmt":"2014-07-31T22:15:18","guid":{"rendered":"http:\/\/blogs.nejm.org\/cardioexchange\/?post_type=voices&#038;p=44392"},"modified":"2014-07-31T18:17:36","modified_gmt":"2014-07-31T22:17:36","slug":"what-does-the-success-of-crispr-mean-for-cholesterol-control","status":"publish","type":"post","link":"https:\/\/blogs.nejm.org\/cardioexchange\/2014\/07\/31\/what-does-the-success-of-crispr-mean-for-cholesterol-control\/","title":{"rendered":"What Does CRISPR&#8217;s Success Mean for Cholesterol Control?"},"content":{"rendered":"<p><a href=\"https:\/\/www.addgene.org\/CRISPR\/guide\/\">CRISPR<\/a> is a new technique for inactivating or editing specific genes. Developed in microorganisms, it also works in mammalian cells, including <a href=\"http:\/\/www.jwatch.org\/na33615\/2014\/02\/06\/new-technique-greatly-improves-search-disease-related\">in vitro human cells<\/a> and <a href=\"http:\/\/www.jwatch.org\/na33707\/2014\/02\/13\/new-precise-gene-editing-technique-works-monkeys\">monkey embryos<\/a>.<\/p>\n<p>About 10 years ago, a gene was identified that is critical to production of the LDL cholesterol receptor (LDL-R): PCSK9. Naturally occurring human mutations that enhance the effect of this gene greatly reduce production of LDL-R in the liver, causing hypercholesterolemia. Conversely, mutations that impair expression of the gene greatly increase production of LDL-R, leading to LDL cholesterol levels that are 40% lower than normal (and coronary heart disease rates that are 90% lower than normal).<\/p>\n<p>In <a href=\"http:\/\/circres.ahajournals.org\/content\/early\/2014\/06\/10\/CIRCRESAHA.115.304351\">a recent study<\/a>, a multi-institutional team used CRISPR to knock out the PCSK9 gene in the livers of mice. A single injection of the virus carrying the CRISPR \u201cmachinery\u201d to the mouse liver led to dramatic increases in LDL-R and decreases in plasma levels of LDL cholesterol. No adverse effects (such as inadvertently knocking out genes other than the target gene) were noted.<\/p>\n<p>The study authors claim the result should be durable and that a single treatment might confer long-term cholesterol reduction, although they do not present proof of this. If this approach works safely in humans, the implications are obvious and enormous.<\/p>\n<p><em><strong>As clinicians, what is your response to this report?<\/strong><\/em><\/p>\n<p><em>This story was adapted from NEJM Journal Watch. You can find the <a href=\"http:\/\/www.jwatch.org\/na34964\/2014\/06\/24\/gene-editing-technique-dramatically-lowers-ldl-cholesterol\">original publication here<\/a>.<\/em><\/p>\n","protected":false},"excerpt":{"rendered":"<p>CRISPR is a new technique for inactivating or editing specific genes. Developed in microorganisms, it also works in mammalian cells, including in vitro human cells and monkey embryos. About 10 years ago, a gene was identified that is critical to production of the LDL cholesterol receptor (LDL-R): PCSK9. Naturally occurring human mutations that enhance the [&hellip;]<\/p>\n","protected":false},"author":967,"featured_media":0,"comment_status":"open","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[1],"tags":[270,1521,533],"class_list":["post-44392","post","type-post","status-publish","format-standard","hentry","category-general","tag-genetics","tag-hypercholesterolemia-treatment","tag-ldl-cholesterol"],"_links":{"self":[{"href":"https:\/\/blogs.nejm.org\/cardioexchange\/wp-json\/wp\/v2\/posts\/44392","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/blogs.nejm.org\/cardioexchange\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/blogs.nejm.org\/cardioexchange\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/blogs.nejm.org\/cardioexchange\/wp-json\/wp\/v2\/users\/967"}],"replies":[{"embeddable":true,"href":"https:\/\/blogs.nejm.org\/cardioexchange\/wp-json\/wp\/v2\/comments?post=44392"}],"version-history":[{"count":0,"href":"https:\/\/blogs.nejm.org\/cardioexchange\/wp-json\/wp\/v2\/posts\/44392\/revisions"}],"wp:attachment":[{"href":"https:\/\/blogs.nejm.org\/cardioexchange\/wp-json\/wp\/v2\/media?parent=44392"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/blogs.nejm.org\/cardioexchange\/wp-json\/wp\/v2\/categories?post=44392"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/blogs.nejm.org\/cardioexchange\/wp-json\/wp\/v2\/tags?post=44392"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}