{"id":6793,"date":"2016-03-31T14:05:24","date_gmt":"2016-03-31T12:05:24","guid":{"rendered":"http:\/\/news.embl.de\/?p=6793"},"modified":"2024-03-25T10:28:14","modified_gmt":"2024-03-25T09:28:14","slug":"1603-designing-gene-therapy","status":"publish","type":"post","link":"https:\/\/www.embl.org\/news\/science\/1603-designing-gene-therapy\/","title":{"rendered":"Designing gene therapy"},"content":{"rendered":"\n<p>Scientists at EMBL have increased the efficiency of a genome-engineering&nbsp;tool called Sleeping Beauty, which is showing promise in clinical trials for leukaemia and lymphoma immunotherapies. In a study published today in <em>Nature Communications<\/em>, they reveal structural information that is likely to lead to further enhancements, ultimately resulting in better patient outcomes.<\/p>\n\n\n\n<p>\u201cBased on the structure, we designed new variants that are already 30% more efficient than the most efficient ones currently available,\u201d says <a href=\"http:\/\/www.embl.de\/research\/units\/scb\/barabas\" target=\"_blank\" rel=\"noopener noreferrer\">Orsolya Barabas<\/a>, who led the work at EMBL. \u201cThat may not sound like a lot, but for patients with only a few months\u2019 prognosis, waiting 3 weeks for a treatment is better than waiting a whole month.\u201d<\/p>\n\n\n\n<p>Sleeping Beauty is a transposon, or \u2018jumping gene\u2019, currently being used in clinical trials for B-cell leukaemias and lymphomas. In these treatments, Sleeping Beauty is used to insert a gene into T-cells \u2013 white blood cells that help to track down and eliminate threats such as disease-causing microbes \u2013 harvested from a patient. The genetically modified T-cells are injected back into the patient, where their new gene enables them to seek out and destroy the cancer cells. The technique is cheaper and easier to apply than current approaches, which mainly rely on modified viruses as deliverymen, so it is rapidly moving into clinical practice, and attracting investment from the pharmaceutical industry.<\/p>\n\n\n\n<blockquote class=\"vf-blockquote\"><p>for patients with only a few months\u2019 prognosis, waiting 3 weeks for a treatment is better than waiting a whole month.<\/p><\/blockquote>\n\n\n\n<p>A bottleneck of this method is that it takes time to engineer and select the therapeutic T-cells. The quicker the T-cells can be modified and transplanted back, the better the treatment prognosis for the patients, and the lower the costs. Until now, however, efforts to increase the treatment\u2019s efficiency were educated guesses, based on the structure of similar molecules. Franka Voigt, a postdoc in Barabas\u2019 lab, determined the 3-dimensional structure of Sleeping Beauty\u2019s active domain. Working with <a href=\"http:\/\/www.pei.de\/EN\/research\/groups\/medical-biotechnology\/transposition-and-genome-engineering\/transposition-and-genome-engineering-node\">Zolt\u00e1n Ivics\u2019 lab<\/a> at the Paul Ehrlich Institute in Germany, the EMBL scientists then used that information to design changes to that structure to make it work better.<\/p>\n\n\n\n<h2 class=\"wp-block-heading\">More efficient than CRISPR<\/h2>\n\n\n\n<p>Transposons like Sleeping Beauty have advantages for therapies that hinge on inserting a gene, compared to other genome engineering&nbsp;approaches such as CRISPR\/Cas9. Researchers can make CRISPR\/Cas9 cut the genome at a specific point \u2013 making it ideal for eliminating genetic errors \u2013 but it doesn\u2019t insert any genetic material; the gene is added separately, and is only one of several options available to the cell\u2019s machinery to repair the cut. By contrast, Sleeping Beauty inserts the extra genetic material directly into the genome \u2013 and the EMBL scientists\u2019 enhancements now make it even more efficient.<\/p>\n\n\n\n<p>\u201cIdeally, you\u2019d want to combine the targeting of CRISPR and the efficiency of Sleeping Beauty \u2013 but that\u2019s proving very, very difficult,\u201d says Barabas, \u201cso it makes sense to pursue the applications that each is best at, at least for the time being.\u201d<\/p>\n\n\n\n<blockquote class=\"vf-blockquote\"><p>it makes sense to pursue the applications that each is best at<\/p><\/blockquote>\n\n\n\n<p>Sleeping Beauty&nbsp;inserts the extra genetic material at random, so there is a risk \u2013 albeit a small one \u2013 that the addition could disrupt the cell\u2019s genome. To minimise this risk, the therapies currently being trialled involve carefully selecting which T-cells to inject back into a patient, which takes time.<\/p>\n\n\n\n<p>The scientists&nbsp;are continuing to design mutations to try to increase Sleeping Beauty\u2019s efficiency even further. In parallel, Barabas\u2019 lab strives to uncover the structure of the whole molecule bound to the DNA that it acts upon, as this could provide insights for further improvements. Such future improvements could make Sleeping Beauty-based therapies feasible for other conditions such as solid tumours, where the current versions of Sleeping Beauty are not efficient enough.<\/p>\n","protected":false},"excerpt":{"rendered":"<p>Information on structure of molecule used for genome engineering yields increased efficiency<\/p>\n","protected":false},"author":8,"featured_media":6796,"comment_status":"closed","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"_acf_changed":false,"footnotes":""},"categories":[2,17591],"tags":[32,43,1748,35],"embl_taxonomy":[],"class_list":["post-6793","post","type-post","status-publish","format-standard","has-post-thumbnail","hentry","category-science","category-science-technology","tag-health","tag-heidelberg","tag-press-release","tag-structural-biology"],"acf":{"article_intro":"<p>Information on structure of molecule used for genome engineering\u00a0yields increased efficiency<\/p>\n","related_links":false,"article_sources":[{"source_description":"<p>Voigt <em>et al.<\/em> <em>Nature Communications<\/em>, 30 March 2016. DOI: 10.1038\/ncomms11126<\/p>\n","source_link_url":"http:\/\/dx.doi.org\/10.1038\/ncomms11126"}],"vf_locked":false,"featured":false,"color":"#007B53","show_featured_image":false,"in_this_article":false,"youtube_url":"","mp4_url":"","video_caption":"","translations":false,"press_contact":"EMBL Generic"},"embl_taxonomy_terms":[],"yoast_head":"<!-- This site is optimized with the Yoast SEO plugin v26.2 - https:\/\/yoast.com\/wordpress\/plugins\/seo\/ -->\n<title>Designing gene therapy | EMBLetc.<\/title>\n<meta name=\"description\" content=\"EMBL scientists designed more efficient versions of Sleeping Beauty genome-engineering tool; could speed up therapies where CRISPR\/Cas9 shows less promise\" \/>\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.embl.org\/news\/science\/1603-designing-gene-therapy\/\" \/>\n<meta property=\"og:locale\" content=\"en_US\" \/>\n<meta property=\"og:type\" content=\"article\" \/>\n<meta property=\"og:title\" content=\"Designing gene therapy | EMBLetc.\" \/>\n<meta property=\"og:description\" content=\"EMBL scientists designed more efficient versions of Sleeping Beauty genome-engineering tool; could speed up therapies where CRISPR\/Cas9 shows less promise\" \/>\n<meta property=\"og:url\" content=\"https:\/\/www.embl.org\/news\/science\/1603-designing-gene-therapy\/\" \/>\n<meta property=\"og:site_name\" content=\"EMBL\" \/>\n<meta property=\"article:publisher\" content=\"https:\/\/www.facebook.com\/embl.org\/\" \/>\n<meta property=\"article:published_time\" content=\"2016-03-31T12:05:24+00:00\" \/>\n<meta property=\"article:modified_time\" content=\"2024-03-25T09:28:14+00:00\" \/>\n<meta property=\"og:image\" content=\"https:\/\/www.embl.org\/news\/wp-content\/uploads\/2016\/03\/pr30mar16-ib.jpg\" \/>\n\t<meta property=\"og:image:width\" content=\"620\" \/>\n\t<meta property=\"og:image:height\" content=\"425\" \/>\n\t<meta property=\"og:image:type\" content=\"image\/jpeg\" \/>\n<meta name=\"author\" content=\"Sonia Furtado Neves\" \/>\n<meta name=\"twitter:card\" content=\"summary_large_image\" \/>\n<meta name=\"twitter:creator\" content=\"@Aur_ora\" \/>\n<meta name=\"twitter:site\" content=\"@embl\" \/>\n<meta name=\"twitter:label1\" content=\"Written by\" \/>\n\t<meta name=\"twitter:data1\" content=\"Sonia Furtado Neves\" \/>\n\t<meta name=\"twitter:label2\" content=\"Est. reading time\" \/>\n\t<meta name=\"twitter:data2\" content=\"3 minutes\" \/>\n<script type=\"application\/ld+json\" class=\"yoast-schema-graph\">{\"@context\":\"https:\/\/schema.org\",\"@graph\":[{\"@type\":\"NewsArticle\",\"@id\":\"https:\/\/www.embl.org\/news\/science\/1603-designing-gene-therapy\/#article\",\"isPartOf\":{\"@id\":\"https:\/\/www.embl.org\/news\/science\/1603-designing-gene-therapy\/\"},\"author\":{\"name\":\"Sonia Furtado Neves\",\"@id\":\"https:\/\/www.embl.org\/news\/#\/schema\/person\/d926199a955624b44dda296f396c5e68\"},\"headline\":\"Designing gene therapy\",\"datePublished\":\"2016-03-31T12:05:24+00:00\",\"dateModified\":\"2024-03-25T09:28:14+00:00\",\"mainEntityOfPage\":{\"@id\":\"https:\/\/www.embl.org\/news\/science\/1603-designing-gene-therapy\/\"},\"wordCount\":633,\"publisher\":{\"@id\":\"https:\/\/www.embl.org\/news\/#organization\"},\"image\":{\"@id\":\"https:\/\/www.embl.org\/news\/science\/1603-designing-gene-therapy\/#primaryimage\"},\"thumbnailUrl\":\"https:\/\/www.embl.org\/news\/wp-content\/uploads\/2016\/03\/pr30mar16-ib.jpg\",\"keywords\":[\"health\",\"heidelberg\",\"press release\",\"structural biology\"],\"articleSection\":[\"Science\",\"Science &amp; 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