{"id":94527,"date":"2019-08-07T09:43:33","date_gmt":"2019-08-07T16:43:33","guid":{"rendered":"https:\/\/lifeboat.com\/blog\/2019\/08\/allele-specific-repair-of-splicing-mutations-in-cystic-fibrosis-through-ascas12a-genome-editing"},"modified":"2019-08-07T09:43:33","modified_gmt":"2019-08-07T16:43:33","slug":"allele-specific-repair-of-splicing-mutations-in-cystic-fibrosis-through-ascas12a-genome-editing","status":"publish","type":"post","link":"https:\/\/lifeboat.com\/blog\/2019\/08\/allele-specific-repair-of-splicing-mutations-in-cystic-fibrosis-through-ascas12a-genome-editing","title":{"rendered":"Allele specific repair of splicing mutations in cystic fibrosis through AsCas12a genome editing"},"content":{"rendered":"<p><a class=\"aligncenter blog-photo\" href=\"https:\/\/lifeboat.com\/blog.images\/allele-specific-repair-of-splicing-mutations-in-cystic-fibrosis-through-ascas12a-genome-editing.jpg\"><\/a><\/p>\n<p>Cystic fibrosis (CF) is an autosomal recessive disease caused by mutations in the <i>CFTR<\/i> gene. The 3272\u201326AG and 3849+10kbCT <i>CFTR<\/i> mutations alter the correct splicing of the <i>CFTR<\/i> gene, generating new acceptor and donor splice sites respectively. Here we develop a genome editing approach to permanently correct these genetic defects, using a single crRNA and the <i><i>Acidaminococcus<\/i> sp. BV3L6<\/i>, AsCas12a. This genetic repair strategy is highly precise, showing very strong discrimination between the wild-type and mutant sequence and a complete absence of detectable off-targets. The efficacy of this gene correction strategy is verified in intestinal organoids and airway epithelial cells derived from CF patients carrying the 3272\u201326AG or 3849+10kbCT mutations, showing efficient repair and complete functional recovery of the CFTR channel. These results demonstrate that allele-specific genome editing with AsCas12a can correct aberrant <i>CFTR<\/i> splicing mutations, paving the way for a permanent splicing correction in genetic diseases.<\/p>\n","protected":false},"excerpt":{"rendered":"<p>Cystic fibrosis (CF) is an autosomal recessive disease caused by mutations in the CFTR gene. The 3272\u201326AG and 3849+10kbCT CFTR mutations alter the correct splicing of the CFTR gene, generating new acceptor and donor splice sites respectively. Here we develop a genome editing approach to permanently correct these genetic defects, using a single crRNA and [\u2026]<\/p>\n","protected":false},"author":396,"featured_media":0,"comment_status":"open","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[11,412],"tags":[],"class_list":["post-94527","post","type-post","status-publish","format-standard","hentry","category-biotech-medical","category-genetics"],"_links":{"self":[{"href":"https:\/\/lifeboat.com\/blog\/wp-json\/wp\/v2\/posts\/94527","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/lifeboat.com\/blog\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/lifeboat.com\/blog\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/lifeboat.com\/blog\/wp-json\/wp\/v2\/users\/396"}],"replies":[{"embeddable":true,"href":"https:\/\/lifeboat.com\/blog\/wp-json\/wp\/v2\/comments?post=94527"}],"version-history":[{"count":0,"href":"https:\/\/lifeboat.com\/blog\/wp-json\/wp\/v2\/posts\/94527\/revisions"}],"wp:attachment":[{"href":"https:\/\/lifeboat.com\/blog\/wp-json\/wp\/v2\/media?parent=94527"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/lifeboat.com\/blog\/wp-json\/wp\/v2\/categories?post=94527"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/lifeboat.com\/blog\/wp-json\/wp\/v2\/tags?post=94527"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}