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<span>What are genome editing and CRISPR-Cas9?</span>
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<h1>What are genome editing and CRISPR-Cas9?</h1>
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<section><div class="mp-content"><p>Genome editing (also called gene editing) is a group of technologies that give scientists the ability to change an organism's DNA. These technologies allow genetic material to be added, removed, or altered at particular locations in the genome. Several approaches to genome editing have been developed. A well-known one is called CRISPR-Cas9, which is short for clustered regularly interspaced short palindromic repeats and CRISPR-associated protein 9. The CRISPR-Cas9 system has generated a lot of excitement in the scientific community because it is faster, cheaper, more accurate, and more efficient than other genome editing methods.</p>
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<p>CRISPR-Cas9 was adapted from a naturally occurring genome editing system that bacteria use as an immune defense. When infected with viruses, bacteria capture small pieces of the viruses' DNA and insert them into their own DNA in a particular pattern to create segments known as CRISPR arrays. The CRISPR arrays allow the bacteria to "remember" the viruses (or closely related ones). If the viruses attack again, the bacteria produce RNA segments from the CRISPR arrays that recognize and attach to specific regions of the viruses' DNA. The bacteria then use Cas9 or a similar enzyme to cut the DNA apart, which disables the virus.</p>
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<p>Researchers adapted this immune defense system to edit DNA. They create a small piece of RNA with a short "guide" sequence that attaches (binds) to a specific target sequence in a cell's DNA, much like the RNA segments bacteria produce from the CRISPR array. This guide RNA also attaches to the Cas9 enzyme. When introduced into cells, the guide RNA recognizes the intended DNA sequence, and the Cas9 enzyme cuts the DNA at the targeted location, mirroring the process in bacteria. Although Cas9 is the enzyme that is used most often, other enzymes (for example Cpf1) can also be used. Once the DNA is cut, researchers use the cell's own DNA repair machinery to add or delete pieces of genetic material, or to make changes to the DNA by replacing an existing segment with a customized DNA sequence.</p>
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<p>Genome editing is of great interest in the prevention and treatment of human diseases. Currently, genome editing is used in cells and animal models in research labs to understand diseases. Scientists are still working to determine whether this approach is safe and effective for <a data-pid="20283" href="https://medlineplus.gov/genetics/understanding/therapy/genetherapy/">use in people</a>. It is being explored in research and clinical trials for a wide variety of diseases, including single-gene disorders such as <a data-pid="14435" href="https://medlineplus.gov/genetics/condition/cystic-fibrosis/">cystic fibrosis</a>, <a data-pid="14515" href="https://medlineplus.gov/genetics/condition/hemophilia/">hemophilia</a>, and <a data-pid="14439" href="https://medlineplus.gov/genetics/condition/sickle-cell-disease/">sickle cell disease</a>. It also holds promise for the treatment and prevention of more <a data-pid="20135" href="https://medlineplus.gov/genetics/understanding/mutationsanddisorders/complexdisorders/">complex diseases</a>, such as cancer, heart disease, mental illness, and human immunodeficiency virus (HIV) infection.</p>
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<p>Ethical concerns arise when genome editing, using technologies such as CRISPR-Cas9, is used to alter human genomes. Most of the changes introduced with genome editing are limited to somatic cells, which are cells other than egg and sperm cells (germline cells). These changes are isolated to only certain tissues and are not passed from one generation to the next. However, changes made to genes in egg or sperm cells or to the genes of an embryo could be passed to future generations. Germline cell and embryo genome editing bring up a number of ethical challenges, including whether it would be permissible to use this technology to enhance normal human traits (such as height or intelligence). Based on concerns about ethics and safety, germline cell and embryo genome editing are currently illegal in the United States and many other countries.</p>
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<h2>Scientific journal articles for further reading</h2>
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<p>Ormond KE(1), Mortlock DP(2), Scholes DT(3), Bombard Y(4), Brody LC(5), Faucett WA(6), Garrison NA(7), Hercher L(8), Isasi R(9), Middleton A(10), Musunuru K(11), Shriner D(12), Virani A(13), Young CE(3). Human Germline Genome Editing. Am J Hum Genet. 2017 Aug 3;101(2):167-176. PubMed: <a href="https://www.ncbi.nlm.nih.gov/pubmed/28777929" target="_blank">28777929</a>. Free full-text available from PubMed Central: <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5544380/" target="_blank">PMC5544380</a>.</p>
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<p>Gupta RM, Musunuru K. Expanding the genetic editing tool kit: ZFNs, TALENs, and CRISPR-Cas9. J Clin Invest. 2014 Oct;124(10):4154-61. doi: 10.1172/JCI72992. Epub 2014 Oct 1. Review. PubMed: <a href="https://www.ncbi.nlm.nih.gov/pubmed/25271723" target="_blank">25271723</a>. Free full-text available from PubMed Central: <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4191047/" target="_blank">PMC4191047</a>.</p>
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<p>Hsu PD, Lander ES, Zhang F. Development and applications of CRISPR-Cas9 for genome engineering. Cell. 2014 Jun 5;157(6):1262-78. doi:10.1016/j.cell.2014.05.010. Review. PubMed: <a href="https://www.ncbi.nlm.nih.gov/pubmed/24906146" target="_blank">24906146</a>. Free full-text available from PubMed Central: <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4343198/" target="_blank">PMC4343198</a>.</p>
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<p>Komor AC, Badran AH, Liu DR. CRISPR-Based Technologies for the Manipulation of Eukaryotic Genomes. Cell. 2017 Apr 20;169(3):559. doi:10.1016/j.cell.2017.04.005. PubMed: <a href="https://www.ncbi.nlm.nih.gov/pubmed/28431253" target="_blank">28431253</a>.</p></div>
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<h2>For more information about CRISPR-Cas9 and other genome editing technologies:</h2>
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<p>The National Human Genome Research Institute has a series of fact sheets about genome editing:<span class="desc-text"><img alt="From the National Institutes of Health" class="imgdesc" height="16" src="https://medlineplus.gov/images/nih.png" title="From the National Institutes of Health" width="25"/></span></p>
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<a href="https://www.genome.gov/about-genomics/policy-issues/what-is-Genome-Editing" target="_blank">Overview of genome editing</a>
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</p>
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||
</li>
|
||
<li>
|
||
<p>
|
||
<a href="https://www.genome.gov/about-genomics/policy-issues/Genome-Editing/How-genome-editing-works" target="_blank">How does genome editing work?</a>
|
||
</p>
|
||
</li>
|
||
<li>
|
||
<p>
|
||
<a href="https://www.genome.gov/about-genomics/policy-issues/Genome-Editing/How-genome-editing-is-used" target="_blank">How is genome editing used?</a>
|
||
</p>
|
||
</li>
|
||
<li>
|
||
<p>
|
||
<a href="https://www.genome.gov/about-genomics/policy-issues/Genome-Editing/ethical-concerns" target="_blank">What are the ethical concerns about genome editing?</a>
|
||
</p>
|
||
</li>
|
||
<li>
|
||
<p>
|
||
<a href="https://www.genome.gov/about-genomics/policy-issues/Genome-Editing/public-opinion" target="_blank">What do people think about genome editing?</a>
|
||
</p>
|
||
</li>
|
||
<li>
|
||
<p>
|
||
<a href="https://www.genome.gov/about-genomics/policy-issues/Genome-Editing/happening-right-now" target="_blank">What’s happening in genome editing right now?</a>
|
||
</p>
|
||
</li>
|
||
</ul>
|
||
<p>
|
||
<a href="https://www.broadinstitute.org/what-broad/areas-focus/project-spotlight/questions-and-answers-about-crispr" target="_blank">Questions and answers about CRISPR</a> are available from the Broad Institute.</p>
|
||
<p>Personal Genetics Education & Dialogue (PGED) has information on <a href="https://pged.org/genome-editing/" rel="noopener noreferrer" target="_blank">Genome Editing</a>.</p>
|
||
<p>Yourgenome.org (from the Wellcome Genome Campus) provides <a href="https://www.yourgenome.org/theme/what-is-crispr-cas9/" rel="noopener noreferrer" target="_blank">information for the public about CRISPR-Cas9</a>.</p>
|
||
<p>ClinicalTrials.gov has a list of <a href="https://clinicaltrials.gov/ct2/results?cond=&term=CRISPR+OR+genome+editing+OR+gene+editing" target="_blank">human studies using genome editing</a> related to various diseases.<span class="desc-text"><img alt="From the National Institutes of Health" class="imgdesc" height="16" src="https://medlineplus.gov/images/nih.png" title="From the National Institutes of Health" width="25"/></span></p>
|
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</aside>
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<div class="bottom">
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||
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||
<section><div class="mp-exp mp-content"><h2>Topics in the Genomic Research chapter</h2><ul><li><a data-pid="20295" href="https://medlineplus.gov/genetics/understanding/genomicresearch/snp/">What are single nucleotide polymorphisms (SNPs)?</a></li><li><a data-pid="20297" href="https://medlineplus.gov/genetics/understanding/genomicresearch/gwastudies/">What are genome-wide association studies?</a></li><li><a data-pid="20303" href="https://medlineplus.gov/genetics/understanding/genomicresearch/pharmacogenomics/">What is pharmacogenomics?</a></li><li>What are genome editing and CRISPR-Cas9?</li></ul><p><a data-pid="20081" href="https://medlineplus.gov/genetics/understanding/">Other chapters in Help Me Understand Genetics</a></p></div>
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