{"id":217839,"date":"2025-09-11T09:36:16","date_gmt":"2025-09-11T09:36:16","guid":{"rendered":"https:\/\/www.europesays.com\/us\/217839\/"},"modified":"2025-09-11T09:36:16","modified_gmt":"2025-09-11T09:36:16","slug":"crispra-reverses-genetic-heart-disease-in-mice","status":"publish","type":"post","link":"https:\/\/www.europesays.com\/us\/217839\/","title":{"rendered":"CRISPRa Reverses Genetic Heart Disease in Mice"},"content":{"rendered":"

An international multidisciplinary team led by scientists at the\u00a0Centro Nacional de Investigaciones Cardiovasculares<\/a>\u00a0(CNIC), with participation from scientists at\u00a0Hospital Universitario Puerta de Hierro<\/a>\u00a0and the\u00a0University of California San Diego<\/a>, has demonstrated for the first time that CRISPR-based gene activation (CRISPRa) can be used to treat genetic heart disease\u00a0in vivo. The study, published in the\u00a0European Heart Journal\u00a0and presented at the European Society of Cardiology Congress in Madrid, paves the way for novel targeted therapies for patients with genetic cardiac disorders. This approach could be especially useful for patients with conditions caused by mutations in genes too large to be targeted with conventional gene therapy.<\/p>\n

The team made this discovery in a new animal model they developed that carries a truncating mutation in the filamin C gene (FLNC). Truncating variants in FLNC (FLNCtv) reduce the amount of Filamin C protein produced and are a frequent cause of genetic dilated cardiomyopathy and left ventricular non-dilated cardiomyopathy. Both diseases predispose patients to severe arrhythmias and increase the risk of sudden cardiac death. There are currently no specific therapies available for this type of mutation, and clinical options are limited to general heart failure treatments and implantable defibrillator devices.<\/p>\n

The researchers developed a mouse model carrying a truncating FLNC mutation that reproduces the electrical abnormalities observed in patients, including increased vulnerability to drug-induced arrhythmias.<\/p>\n

To restore gene function, the team designed a CRISPRa-based gene-therapy system packaged in a cardiotropic adeno-associated virus (AAVMYO). \u201cThis system does not cut DNA,\u201d explains study first author Dr. Rodrigo Ca\u00f1as \u00c1lvaro, \u201cbut instead uses a nuclease-inactive CRISPR protein fused to a transcriptional activator to switch on the FLNC promoter, thereby increasing Filamin production in the heart.\u201d<\/p>\n

After administration of the vector to adult mutant mice, the researchers observed normalization of FLNC RNA and protein expression to the levels found in healthy animals. Electrocardiogram recordings showed recovery of QRS amplitude and, most importantly, the complete disappearance of flecainide-induced arrhythmias.<\/p>\n

\u201cThis study demonstrates for the first time that CRISPRa gene activation can reverse manifestations of a hereditary cardiomyopathy in an animal model,\u201d says\u00a0Dr. Enrique Lara-Pezzi<\/a>, a CNIC and\u00a0CIBERCV\u00a0<\/a>investigator and the lead author on the study. \u201cOur results suggest that even after the disease has developed, it is possible to restore the heart\u2019s electrical function through a targeted approach.\u201d<\/p>\n

Study collaborator\u00a0Dr. Pablo Garcia-Pav\u00eda<\/a>\u2014head of the Inherited Cardiac Diseases Unit at\u00a0Hospital Universitario Puerta de Hierro, CNIC and CIBERCV investigator\u2014stresses the significance of the findings. \u201cThis research establishes the basis for the development of CRISPRa-AAV therapies not only for FLNC mutations but also for other cardiac disorders caused by insufficient production of essential proteins that cannot be targeted by conventional gene therapy.\u201d<\/p>\n

Reference:\u00a0<\/b>Ca\u00f1as-Alvaro R, Lalaguna L, Rubio B, et al. CRISPR activation to repair electrocardiogram abnormalities caused by a FLNC truncating variant in mice. Eur Heart J. 2025:ehaf703. doi:\u00a010.1093\/eurheartj\/ehaf703<\/a><\/p>\n

This article has been republished from the following materials<\/a>. Note: material may have been edited for length and content. For further information, please contact the cited source. Our press release publishing policy can be accessed here<\/a>.<\/p>\n","protected":false},"excerpt":{"rendered":"An international multidisciplinary team led by scientists at the\u00a0Centro Nacional de Investigaciones Cardiovasculares\u00a0(CNIC), with participation from scientists at\u00a0Hospital…\n","protected":false},"author":3,"featured_media":217840,"comment_status":"","ping_status":"","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[26],"tags":[815,159,67,132,68],"class_list":{"0":"post-217839","1":"post","2":"type-post","3":"status-publish","4":"format-standard","5":"has-post-thumbnail","7":"category-genetics","8":"tag-genetics","9":"tag-science","10":"tag-united-states","11":"tag-unitedstates","12":"tag-us"},"share_on_mastodon":{"url":"https:\/\/pubeurope.com\/@us\/115184995106739144","error":""},"_links":{"self":[{"href":"https:\/\/www.europesays.com\/us\/wp-json\/wp\/v2\/posts\/217839","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/www.europesays.com\/us\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/www.europesays.com\/us\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/www.europesays.com\/us\/wp-json\/wp\/v2\/users\/3"}],"replies":[{"embeddable":true,"href":"https:\/\/www.europesays.com\/us\/wp-json\/wp\/v2\/comments?post=217839"}],"version-history":[{"count":0,"href":"https:\/\/www.europesays.com\/us\/wp-json\/wp\/v2\/posts\/217839\/revisions"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/www.europesays.com\/us\/wp-json\/wp\/v2\/media\/217840"}],"wp:attachment":[{"href":"https:\/\/www.europesays.com\/us\/wp-json\/wp\/v2\/media?parent=217839"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/www.europesays.com\/us\/wp-json\/wp\/v2\/categories?post=217839"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/www.europesays.com\/us\/wp-json\/wp\/v2\/tags?post=217839"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}