Wellcome Sanger Institute

Gene Editing

Cellular Operations

In collaboration with our colleagues in Cellular Operations and Stem Cell Informatics, our work focuses on supporting and delivering the gene editing requirements of the Institute's faculty and research programmes.
  • Through the adoption and implementation of modern genome editing techniques, we tailor our technical experience to help answer biological questions.
  • We optimise, develop and democratise the delivery of genome editing tools and platforms for the Institute’s research programmes.
  • For our collaborating partners we provide an agile, project focused, cost effective and efficient service as well as develop and provide biological resources, technical support and training for research groups and their staff.

Background        

Gene editing (or genetic engineering) is a group of technologies that provide the ability to insert, delete, modify or replace the DNA in a living organism. In research, site specific gene modification is an established method to interrogate the function of genes (or gene products) in cells and organisms in both health and disease.

Revolutionary developments in genome editing techniques and methodologies have vastly improved the ability of researchers to perform site specific genetic engineering. In particular, the use of DNA nucleases such as ZINC fingers (ZFNs), transcription activator-like effectors (TALENs), and more recently the bipartite CRISPR-Cas system, have been key proponents to advancements in the field. These engineered nucleases, often referred to as ‘molecular scissors’, combine site specific genomic recognition with their ability to ‘cut’ DNA. Once DNA is cleaved the natural repair pathways of a cell attempt to repair the damaged DNA sequence. Repair via non-homologous end joining (NHEJ) can result in unsolicited insertions or deletions of nucleotides at the site of DNA cleavage and may cause disruption of normal gene function (i.e. loss of function). When paired with a repair or donor template (a fragment of DNA with known, predetermined sequence) precise insertion of DNA, via homology directed repair (HDR) can be achieved, such as the introduction of a specific mutation.

Resources

The ever expanding gene editing ‘tool-box’ enables researchers to permanently edit genes as well as perturb or tweak gene expression through the use of dCas9-fusion proteins.

The Gene Editing team routinely acquires, develops and tests novel CRIPSR-Cas and other gene editing reagents, resources which contribute to the Institute’s wider research goals.

Gene Editing Platforms

Building on the work of previous Sanger alumnus, Prof. Bill Skarnes and in concert with the Cellular Operations Research and Development team, lead by Andrew Bassett (https://www.sanger.ac.uk/group/gene-editing-and-cellular-research-and-development), we have developed a number of pipelines that establish loss of function (gene ablation) or precise genetic mutant cell lines.

These are used to model the effects of normal gene disruption in health and disease, such as those observed in developmental disorders (https://www.sanger.ac.uk/collaboration/deciphering-developmental-disorders-ddd). These work-flows have been optimised in the generation of some 1,400 mutant induced pluripotent stem cells (iPSCs). More recently, work has begun on expanding the use of these platforms to edit the genomes of primary human cell types, including cells of the haematopoietic system.

Allied to our efforts using CRISPR-Cas we also use well developed platforms to generate large numbers of traditional gene targeting vectors for organisms not amenable to gene targeting using CRISPR or TALENS, such as the malaria parasite P. berghei.

Large Scale Genetic Screening

CRISPR/Cas genome editing tools are extremely amenable to multiplexing and as such are the ‘go to’ tool for performing genome wide genetic perturbation screens. Via pooled or arrayed screening research teams are identifying candidate genes or genetic interactions responsible for a particular phenotype or disease susceptibility. This ability to inform genotype – phenotype interactions in a high throughput manner is empowering the large scale identification of biological networks and the next level of drug discovery. These are also powerful tools to examine the direct effects of a gene, gene variant or gene perturbation on a biological outcome and when combined with single cell –omics, a genotype – phenotype relationship can be determined at the level of a single cell.

The Gene Editing team has developed platforms for generating both arrayed and pooled libraries. In close collaboration with the Cellular Operations Research and Development team, the wider Institute Faculty and external collaborators we are involved in the evolution of these technologies and aim to further develop their design, generation and delivery.

We also have expertise in the use of transposons, genetic elements which can be mobilised in a cell or organism by enzymes known as transposases. Once mobilised, these elements insert randomly into an organisms genome and can activate or disrupt transcription of neighbouring genes (i.e. random insertional mutagenesis).

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                            [post_excerpt] => Our research focuses on the application of large-scale genomic analysis to unravel the spectrum of human genetic variation associated with <span title="... cardiometabolic diseases, and its interaction with non-genetic and environmental cues.">...</span>
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                            [post_name] => soranzo-group
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                            [post_modified] => 2020-01-28 16:26:18
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                            [post_date] => 2015-06-30 15:01:47
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                            [post_content] => 
                            [post_title] => Cellular Generation and Phenotyping
                            [post_excerpt] => The Cellular Generation and Phenotyping (CGaP) core facility provides central cell biology support to the Sanger Institute, functioning as a contract&nbsp;<span title="... research group in partnership with faculty groups to carry out multiple, distinct and often large-scale cell biology projects. Some examples of our work include finding the genes essential to cancer cell survival, and the causes of rare developmental disorders. We also contribute to the COVID-19 Genomics UK consortium.">...</span>
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                            [post_name] => cellular-generation-and-phenotyping
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                            [post_modified] => 2020-09-24 15:35:34
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                            [post_content] => 
                            [post_title] => Vidal-Puig Group
                            [post_excerpt] => We aim to learn why being obese causes metabolic and cardiovascular problems and to provide the rational for mechanistically driven therapeutic&nbsp;<span title="... approaches to prevent these complications which are the meain cause of morbidity among obese patients.">...</span>
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                            [post_date] => 2015-06-11 12:01:25
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                            [post_content] => 
                            [post_title] => Anderson Group
                            [post_excerpt] => The goal of our research is to use high-throughput screens to gain causal insights into the biological basis of human disease,&nbsp;<span title="... identify new drug targets and determine the patients who will benefit most from these drugs. We focus on immune-mediated disease, and inflammatory bowel disease in particular, due to the significant burden of disease and the accessibility of disease relevant tissue.">...</span>
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                            [post_content] => 
                            [post_title] => Parts Group
                            [post_excerpt] => Our goal is to understand how genetic background influences outcome of mutations. To do so, we measure, model, and modulate cell&nbsp;<span title="... state across healthy and disease-relevant human genetic diversity. In the lab, we develop tools for genetic perturbations, and use genome engineering and synthetic biology to create cell lines for screening cellular traits. In the office, we develop probabilistic models as well as software tools to accurately and efficiently analyse the readouts.">...</span>
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    [introduction] => In collaboration with our colleagues in Cellular Operations and Stem Cell Informatics, our work focuses on supporting and delivering the gene editing requirements of the Institute's faculty and research programmes.
    [links] => 
    [partners_introduction] => We work with the following groups
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                            [post_date] => 2019-02-20 15:13:02
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                            [post_content] => 
                            [post_title] => Cellular Operations
                            [post_excerpt] => Cellular Operations provide cell biology support and expertise to the institute.
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                            [post_name] => cellular-generation
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    [publications] => geneedit 
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                            [post_date] => 2015-08-18 15:11:03
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                            [post_content] => 
                            [post_title] => Deciphering Developmental Disorders (DDD)
                            [post_excerpt] => The aim of the Deciphering Developmental Disorders (DDD) Study is to advance clinical genetic practice for children with developmental disorders by <span title="... the systematic application of the latest microarray and sequencing methods while addressing the new ethical challenges raised.">...</span>
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                            [post_name] => deciphering-developmental-disorders-ddd
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                            [post_date] => 2015-09-30 13:47:31
                            [post_date_gmt] => 2015-09-30 13:47:31
                            [post_content] => <p>This tool was developed by Bill Skarnes (Faculty - Stem Cell Engineering), Vivek Iyer, Alex Hodgkins, Saj Perera, David Parry-Smith, Tiago Grego and Anna Farne (Stem Cell Informatics)</p><h5>General Introduction</h5><p>WGE is a highly interactive, web-based visual tool that employs an embedded genome browser and database to assist scientists in designing genome editing strategies using the CRISPR/Cas9 system.</p><p>Genome editing is the science of altering specific portions of DNA so that it behaves in a subtly different way within a cell. For example, we can use genome editing to prevent specific genes from being translated and subsequently transcribed into functioning proteins. In this way we can examine the role genes play in the life of the cell, potentially shedding valuable light on the causes of disease.</p><p>Proteins are the workhorse molecues of the cell, they provide physical structure to cells as well as carrying out work by ensuring chemical reactions occur in the right order, using the correct amount of energy and the appropriate ancillary molecules. Even a single unit of a protein, known as an amino acid residue, that is wrong can lead to debilitating disease. For example, <a href="https://en.wikipedia.org/wiki/Sickle-cell_disease#Genetics" target="_blank" rel="noopener noreferrer">sickle cell anaemia</a> is due to a single amino acid change that makes haemoglobin too sticky.</p><p>DNA is the molecule that carries the genetic code that specifies the sequence of amino acid resides in the protein products of the cell. It also carries a lot of information in non amino acid encoding regions that guides the way genes are expressed. Any of these regions could be the targets for genome editing campaigns.</p><h5>Detailed Description</h5><p>The rapid development of CRISPR-Cas9 mediated genome editing techniques has given rise to a number of online and stand-alone tools to find and score CRISPR sites for whole genomes. The Wellcome Trust Sanger Institute Genome Editing database (WGE), uses novel methods to compute, visualize and select optimal CRISPR sites in a genome browser environment. The WGE database currently stores single and paired CRISPR sites and pre-calculated off-target information for CRISPRs located in the mouse and human exomes. Scoring and display of off-target sites is simple, and intuitive, and filters can be applied to identify high-quality CRISPR sites rapidly. WGE also provides a tool for the design and display of gene targeting vectors in the same genome browser, along with gene models, protein translation and variation tracks. WGE is open, extensible and can be set up to compute and present CRISPR sites for any genome. <a href="http://www.ncbi.nlm.nih.gov/pubmed/25979474" target="_blank" rel="noopener noreferrer"><cite>[Hodgkins et al., 2015]</cite></a></p><p>The WGE website presents two tools for assisting genome editing:</p><ul><li>a CRISPR finder</li><li>a Gibson assembly PCR oligo designer</li></ul><p>The CRISPR-finding part of the WGE website requires the user to select a species&mdash;currently human or mouse&mdash;and the marker symbol of the gene to inspect. The target Ensembl exon is then selected from a list. All possible CRISPR sites and paired sites are shown on a scrollable Genoverse genome browser view. This incorporates the current gene models from Ensembl, protein translation, available variation and any user-generated targeting vector designs. &lsquo;Paired&rsquo; CRISPR sites for applications using Cas9 nickases are shown in WGE when CRISPR sites on opposite strands have a separation of up to 30&thinsp;bp, or an overlap of up to 10&thinsp;bp. <a href="http://www.ncbi.nlm.nih.gov/pubmed/24584192" target="_blank" rel="noopener noreferrer"><cite>[Shen et al., 2014]</cite></a></p><h6>Scoring Off-targets</h6><p>Our scoring system reports the number of similar sequences in the genome with up to four mismatches (excluding the PAM region). A string such as &lsquo;0:1, 1:0, 2:0, 3:4, 4:56&rsquo; indicates that there is 1 genomic site with 0 mismatches (the CRISPR site itself), no off-target sites with 1 or 2 mismatches, and an increasing number of potential off-target sites with 3 and 4 mismatches. In this way, users can immediately grasp the off-target potential for each CRISPR site.</p><p>Users can also filter CRISPR sites based on their stored off-target characteristics. Using this interface, hundreds of possible CRISPR sites can be narrowed down and evaluated to select the optimal site(s) for an editing task.</p><h6>Gibson Assembly Designer</h6><p>WGE can be used to design PCR primers for the assembly of gene targeting vectors by Gibson assembly or other similar PCR-based methods. This involves first choosing a target exon, and then adjusting design parameters via a web interface to allow the primer calculations to be run. The resulting targeting vector designs can be bookmarked, edited, and are displayed alongside CRISPR sites in the genome browser.</p><p>WGE contains comprehensive help and an application programming interface that enables users to build their own CRISPR indexes for specific projects.</p><p>See the publications below for further details.</p>
                            [post_title] => WGE - CRISPR design tool
                            [post_excerpt] => WTSI Genome Editing (WGE) is a website and database that provides tools for designing genome editing of human and mouse genomes&nbsp;<span title="... using CRISPR/Cas9">...</span>
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                            [post_name] => wge
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                            [post_modified] => 2020-08-28 13:06:38
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                            [post_date] => 2015-09-18 15:49:01
                            [post_date_gmt] => 2015-09-18 15:49:01
                            [post_content] => <p class="MsoNoSpacing" style="margin:0cm 0cm 0.0001pt; text-align:justify"><span style="font-size:10pt"><span style="line-height:150%"><span style="font-family:&quot;Arial&quot;,&quot;sans-serif&quot;">Plasmo<span style="font-family:&quot;Arial&quot;,&quot;sans-serif&quot;">GEM</span> is a non-profit, open-access malaria research resource, providing tools for the manipulation of <em><span style="font-family:&quot;Arial&quot;,&quot;sans-serif&quot;">Plasmodium</span></em> genomes, and using them to carry out large-scale research projects. These tools currently include:</span></span></span></p><p class="MsoNoSpacing" style="margin:0cm 0cm 0.0001pt; text-align:justify"></p><p class="MsoNoSpacing" style="margin:0cm 0cm 0.0001pt; text-align:justify"><em><strong><span style="font-size:10pt"><span style="line-height:150%"><span style="font-family:&quot;Arial&quot;,&quot;sans-serif&quot;">P. berghei</span></span></span></strong></em></p><p class="MsoNoSpacing" style="margin:0cm 0cm 0.0001pt; text-align:justify"><span style="font-size:10pt"><span style="line-height:150%"><span style="font-family:&quot;Arial&quot;,&quot;sans-serif&quot;">We have produced large numbers of DNA vectors for the targeted manipulation of <em>P. berghei</em><i> </i>genes. Resources available currently include: </span></span></span></p><ul><li class="MsoNoSpacing" style="margin:0cm 0cm 0.0001pt; text-align:justify"><span style="font-size:10pt"><span style="line-height:150%"><span style="font-family:&quot;Arial&quot;,&quot;sans-serif&quot;">A large-insert (6-10kb) <em>P. berghei</em> genomic library covering &gt;90% of <em>P. berghei</em> genes</span></span></span></li><li class="MsoNoSpacing" style="margin:0cm 0cm 0.0001pt; text-align:justify"><span style="font-size:10pt"><span style="line-height:150%"><span style="font-family:&quot;Arial&quot;,&quot;sans-serif&quot;">A library of artificial chromosomes covering &gt;3500 <em>P. berghei</em> genes for use in complementation or over-expression studies.</span></span></span></li><li class="MsoNoSpacing" style="margin:0cm 0cm 0.0001pt; text-align:justify"><span style="font-size:10pt"><span style="line-height:150%"><span style="font-family:&quot;Arial&quot;,&quot;sans-serif&quot;">Gene targeting vectors for the disruption of &gt;2600 <em>P. berghei</em> genes and epitope tagging of &gt;400 genes. We are currently expanding our knockout library to attempt to cover the entire genome, excluding large multi-gene families such as <i>birs. </i></span></span></span></li><li class="MsoNoSpacing" style="margin:0cm 0cm 0.0001pt; text-align:justify"><span style="font-size:10pt"><span style="line-height:150%"><span style="font-family:&quot;Arial&quot;,&quot;sans-serif&quot;">Blood-stage growth phenotypes for &gt;2,600 genes, generated using barcode sequencing after pooled transfection with our gene targeting knock out vectors</span></span></span></li></ul><p class="MsoNoSpacing" style="margin:0cm 0cm 0.0001pt; text-align:justify"><img class="wp-image-112901 aligncenter" src="/wp-content/uploads/oct2018__p.berghei.jpg" alt="" width="718" height="644" data-credit="" /></p><p class="MsoNoSpacing" style="margin:0cm 0cm 0.0001pt; text-align:justify"><span style="font-size:10pt"><span style="line-height:150%"><span style="font-family:&quot;Arial&quot;,&quot;sans-serif&quot;">All the tools as well as phenotypic data currently available can be found <u><strong><a href="https://plasmogem.sanger.ac.uk/">here</a></strong></u>.</span></span></span></p><p class="MsoNoSpacing" style="margin:0cm 0cm 0.0001pt; text-align:justify"></p><p class="MsoNoSpacing" style="margin:0cm 0cm 0.0001pt; text-align:justify"><em><strong><span style="font-size:10pt"><span style="line-height:150%"><span style="font-family:&quot;Arial&quot;,&quot;sans-serif&quot;">P. falciparum:</span></span></span></strong></em></p><p class="MsoNoSpacing" style="margin:0cm 0cm 0.0001pt; text-align:justify"><span style="font-size:10pt"><span style="line-height:150%"><span style="font-family:&quot;Arial&quot;,&quot;sans-serif&quot;">PlasmoGEM is currently generating vectors for Cas9 and gRNA expression (pDC2) as well as barcoded homologous repair (HR) templates (pCC1) for 200-300 <em>P.falciparum</em> genes. </span></span></span></p><p class="MsoNoSpacing" style="margin:0cm 0cm 0.0001pt; text-align:justify"></p><p class="MsoNoSpacing" style="margin:0cm 0cm 0.0001pt; text-align:justify"><img class="wp-image-112902 aligncenter" src="/wp-content/uploads/oct2018__p.falciparum.jpg" alt="" width="857" height="539" data-credit="" /></p><p class="MsoNoSpacing" style="margin:0cm 0cm 0.0001pt; text-align:justify"><em><strong><span style="font-size:10pt"><span style="line-height:150%"><span style="font-family:&quot;Arial&quot;,&quot;sans-serif&quot;">P. knowlesi:</span></span></span></strong></em></p><p class="MsoNoSpacing" style="margin:0cm 0cm 0.0001pt; text-align:justify"><span style="font-size:10pt"><span style="line-height:150%"><span style="font-family:&quot;Arial&quot;,&quot;sans-serif&quot;">PlasmoGEM is currently generating vectors for Cas9 and gRNA expression (pK-U6Cas9) as well as barcoded homologous repair (HR) templates by PCR for 400-500 <em>P. knowlesi</em><i> </i>genes.</span></span></span></p><p style="margin:0cm 0cm 8pt"></p><p style="margin:0cm 0cm 8pt"><img class="wp-image-112903 aligncenter" src="/wp-content/uploads/oct2018__p.knowlesi.jpg" alt="" width="677" height="187" data-credit="" /></p>
                            [post_title] => PlasmoGEM - TOOLS
                            [post_excerpt] => Plasmo <em>GEM</em> is a non-profit, open-access malaria research resource, providing tools for the manipulation of <em>Plasmodium</em> genomes, and using them <span title="... to carry out large-scale research projects.">...</span>
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                            [post_content] => 
                            [post_title] => HipSci
                            [post_excerpt] => Hundreds of induced pluripotent stem cell lines for cellular genetic analysis
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    [research_introduction] => 
    [secondary_title] => Cellular Operations
    [slideshow] => 
    [title] => Gene Editing
    [twitter] => @sangerinstitute
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                                    [post_date] => 2017-02-21 05:30:01
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                                    [post_content] => 
                                    [post_title] => Thomas, Mark
                                    [post_excerpt] => Involved in the annotation of the human and mouse genomes, I have a particular interest in noncoding transcription. With expertise <span title="... in genome interpretation, I currently support gene editing activities at the Wellcome Sanger Institute.">...</span>
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                                    [post_content] => 
                                    [post_title] => Skelton, Jason
                                    [post_excerpt] => 
                                    [post_status] => publish
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                                    [post_date] => 2019-06-04 07:00:01
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                                    [post_content] => 
                                    [post_title] => Bruntraeger, Michaela
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                                    [post_content] => 
                                    [post_title] => Byrne, Meg
                                    [post_excerpt] => I am using CRISPR-Cas technologies to modify targeted loci in iPS cells for use in studying disease.
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                                    [post_date] => 2019-05-29 13:28:28
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                                    [post_content] => 
                                    [post_title] => Newman, Ben
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                    [content] => <ul>
<li>Through the adoption and implementation of modern genome editing techniques, we tailor our technical experience to help answer biological questions.</li>
<li>We optimise, develop and democratise the delivery of genome editing tools and platforms for the Institute’s research programmes.</li>
<li>For our collaborating partners we provide an agile, project focused, cost effective and efficient service as well as develop and provide biological resources, technical support and training for research groups and their staff.</li>
</ul>
<p><strong>Background         </strong></p>
<p><img loading="lazy" class="wp-image-114072 alignright" src="/wp-content/uploads/nov2019__extrenal_webpageasset_5.png" alt="" width="395" height="109" data-credit="" />Gene editing (or genetic engineering) is a group of technologies that provide the ability to insert, delete, modify or replace the DNA in a living organism. In research, site specific gene modification is an established method to interrogate the function of genes (or gene products) in cells and organisms in both health and disease.</p>
<p>Revolutionary developments in genome editing techniques and methodologies have vastly improved the ability of researchers to perform site specific genetic engineering. In particular, the use of DNA nucleases such as ZINC fingers (ZFNs), transcription activator-like effectors (TALENs), and more recently the bipartite CRISPR-Cas system, have been key proponents to advancements in the field. These engineered nucleases, often referred to as ‘molecular scissors’, combine site specific genomic recognition with their ability to ‘cut’ DNA. Once DNA is cleaved the natural repair pathways of a cell attempt to repair the damaged DNA sequence. Repair via non-homologous end joining (NHEJ) can result in unsolicited insertions or deletions of nucleotides at the site of DNA cleavage and may cause disruption of normal gene function (i.e. loss of function). When paired with a repair or donor template (a fragment of DNA with known, predetermined sequence) precise insertion of DNA, via homology directed repair (HDR) can be achieved, such as the introduction of a specific mutation.</p>
<p><strong>Resources</strong></p>
<p>The ever expanding gene editing ‘tool-box’ enables researchers to permanently edit genes as well as perturb or tweak gene expression through the use of dCas9-fusion proteins.</p>
<p>The Gene Editing team routinely acquires, develops and tests novel CRIPSR-Cas and other gene editing reagents, resources which contribute to the Institute’s wider research goals.</p>
<p><strong><strong>Gene Editing Platforms</strong></strong></p>
<p>Building on the work of previous Sanger alumnus, Prof. Bill Skarnes and in concert with the Cellular Operations Research and Development team, lead by Andrew Bassett (<a href="https://www.sanger.ac.uk/group/gene-editing-and-cellular-research-and-development/">https://www.sanger.ac.uk/group/gene-editing-and-cellular-research-and-development</a>), we have developed a number of pipelines that establish loss of function (gene ablation) or precise genetic mutant cell lines.</p>
<p>These are used to model the effects of normal gene disruption in health and disease, such as those observed in developmental disorders (<a href="https://www.sanger.ac.uk/collaboration/deciphering-developmental-disorders-ddd/">https://www.sanger.ac.uk/collaboration/deciphering-developmental-disorders-ddd</a>). These work-flows have been optimised in the generation of some 1,400 mutant induced pluripotent stem cells (iPSCs). More recently, work has begun on expanding the use of these platforms to edit the genomes of primary human cell types, including cells of the haematopoietic system.</p>
<p>Allied to our efforts using CRISPR-Cas we also use well developed platforms to generate large numbers of traditional gene targeting vectors for organisms not amenable to gene targeting using CRISPR or TALENS, such as the malaria parasite P. berghei.</p>
<p><img loading="lazy" class="wp-image-113842 aligncenter" src="/wp-content/uploads/sep2019__asset_2_0.png" alt="" width="2271" height="892" data-credit="" srcset="https://www.sanger.ac.uk/wp-content/uploads/sep2019__asset_2_0.png 2271w, https://www.sanger.ac.uk/wp-content/uploads/sep2019__asset_2_0-1920x754.png 1920w, https://www.sanger.ac.uk/wp-content/uploads/sep2019__asset_2_0-800x314.png 800w" sizes="(max-width: 2271px) 100vw, 2271px" /></p>
<p><strong>Large Scale Genetic Screening</strong></p>
<p>CRISPR/Cas genome editing tools are extremely amenable to multiplexing and as such are the ‘go to’ tool for performing genome wide genetic perturbation screens. Via pooled or arrayed screening research teams are identifying candidate genes or genetic interactions responsible for a particular phenotype or disease susceptibility. This ability to inform genotype – phenotype interactions in a high throughput manner is empowering the large scale identification of biological networks and the next level of drug discovery. These are also powerful tools to examine the direct effects of a gene, gene variant or gene perturbation on a biological outcome and when combined with single cell –omics, a genotype – phenotype relationship can be determined at the level of a single cell.</p>
<p>The Gene Editing team has developed platforms for generating both arrayed and pooled libraries. In close collaboration with the Cellular Operations Research and Development team, the wider Institute Faculty and external collaborators we are involved in the evolution of these technologies and aim to further develop their design, generation and delivery.</p>
<p>We also have expertise in the use of transposons, genetic elements which can be mobilised in a cell or organism by enzymes known as transposases. Once mobilised, these elements insert randomly into an organisms genome and can activate or disrupt transcription of neighbouring genes (i.e. random insertional mutagenesis).</p>
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    [created_at] => 2019-09-11 15:29:44
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                            [post_title] => Stem Cell Informatics
                            [post_excerpt] => Stem Cell Informatics (SCI) develops custom laboratory information systems (LIMS) and computational research tools (WGE) for high-throughput laboratory analysis of human&nbsp;<span title="... stem cells.">...</span>
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                            [post_title] => Vassiliou Group
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                            [post_title] => Bayraktar Group
                            [post_excerpt] => We seek to explore the vast cellular diversity in the human brain using large-scale spatial transcriptomics, imaging and functional screens.
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                            [post_title] => Hurles Group
                            [post_excerpt] => The Hurles group studies the genetic causes and mechanisms of rare genetic disorders and how DNA mutates as it is pass&nbsp;<span title="... on from one generation to the next.">...</span>
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                            [post_title] => Garnett Group
                            [post_excerpt] => The Translational Cancer Genomics team investigate how genetic alterations in cancer contribute to disease and impact on response to therapy.
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                            [post_title] => Thomson Group
                            [post_excerpt] => The bacterial genomics and evolution team focuses primarily on using whole-genome sequencing approaches to study the patterns and drivers for historical&nbsp;<span title="... and ongoing pathogen genome evolution. This is then combined with screens in whole cells or model organisms to understand the phenotypic consequences of those changes.">...</span>
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                            [post_title] => Gene Editing and Cellular Research and Development
                            [post_excerpt] => We develop novel genome editing techniques, cellular differentiation and cellular phenotyping systems, especially with respect to high-throughput investigation of gene and&nbsp;<span title="... non-coding regulatory element function.">...</span>
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                            [post_title] => Adams Group
                            [post_excerpt] => We are a team of cancer biologists, geneticists and computational biologists interested in understanding how cancers develop and the ways of&nbsp;<span title="... controlling their growth. We work on a range of malignancies but are particularly interested in melanoma and other skin cancers.">...</span>
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                            [post_title] => Soranzo Group
                            [post_excerpt] => Our research focuses on the application of large-scale genomic analysis to unravel the spectrum of human genetic variation associated with <span title="... cardiometabolic diseases, and its interaction with non-genetic and environmental cues.">...</span>
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                            [post_title] => Cellular Generation and Phenotyping
                            [post_excerpt] => The Cellular Generation and Phenotyping (CGaP) core facility provides central cell biology support to the Sanger Institute, functioning as a contract&nbsp;<span title="... research group in partnership with faculty groups to carry out multiple, distinct and often large-scale cell biology projects. Some examples of our work include finding the genes essential to cancer cell survival, and the causes of rare developmental disorders. We also contribute to the COVID-19 Genomics UK consortium.">...</span>
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                            [post_title] => Vidal-Puig Group
                            [post_excerpt] => We aim to learn why being obese causes metabolic and cardiovascular problems and to provide the rational for mechanistically driven therapeutic&nbsp;<span title="... approaches to prevent these complications which are the meain cause of morbidity among obese patients.">...</span>
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                            [post_title] => Anderson Group
                            [post_excerpt] => The goal of our research is to use high-throughput screens to gain causal insights into the biological basis of human disease,&nbsp;<span title="... identify new drug targets and determine the patients who will benefit most from these drugs. We focus on immune-mediated disease, and inflammatory bowel disease in particular, due to the significant burden of disease and the accessibility of disease relevant tissue.">...</span>
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                            [post_title] => Parts Group
                            [post_excerpt] => Our goal is to understand how genetic background influences outcome of mutations. To do so, we measure, model, and modulate cell&nbsp;<span title="... state across healthy and disease-relevant human genetic diversity. In the lab, we develop tools for genetic perturbations, and use genome engineering and synthetic biology to create cell lines for screening cellular traits. In the office, we develop probabilistic models as well as software tools to accurately and efficiently analyse the readouts.">...</span>
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Core team

Photo of Tabea Nimz

Tabea Nimz

Advanced Research Assistant

Photo of Dr Sophie Leacock

Dr Sophie Leacock

Advanced Research Assistant

Photo of Ben Newman

Ben Newman

Advanced Research Assistant

Photo of Michaela Bruntraeger

Michaela Bruntraeger

Advanced Research Assistant

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Dr Meg Byrne, EngD

Senior Research Assistant

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Dr Mark Thomas

Senior Computer Biologist

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