[{"command":"settings","settings":{"ajaxPageState":{"theme":"hm_theme","theme_token":"eX9nSXiMTqLUVhY5hjn1iuzezTJkoWeks3sMAb8hMuc","libraries":"eJwDAAAAAAE"},"ajaxTrustedUrl":{"form_action_p_pvdeGsVG5zNF_XLGPTvYSKCf43t8qZYSwcfZl2uzM":true},"pluralDelimiter":"\u0003","user":{"uid":0,"permissionsHash":"2af85631393b514cbde3779a1f71d92618d53b94b54ea1960d28b2e2d121ff12"}},"merge":true},{"command":"openDialog","selector":"#drupal-modal","settings":null,"data":"\u003Cdiv id=\u0022republish_modal_form\u0022\u003E\u003Cform class=\u0022modal-form-example-modal-form ecl-form\u0022 data-drupal-selector=\u0022modal-form-example-modal-form\u0022 action=\u0022\/en\/article\/modal\/7174\u0022 method=\u0022post\u0022 id=\u0022modal-form-example-modal-form\u0022 accept-charset=\u0022UTF-8\u0022\u003E\u003Cp\u003EHorizon articles can be republished for free under the Creative Commons Attribution 4.0 International (CC BY 4.0) licence.\u003C\/p\u003E\n \u003Cp\u003EYou must give appropriate credit. We ask you to do this by:\u003Cbr \/\u003E\n 1) Using the original journalist\u0027s byline\u003Cbr \/\u003E\n 2) Linking back to our original story\u003Cbr \/\u003E\n 3) Using the following text in the footer: This article was originally published in \u003Ca href=\u0027#\u0027\u003EHorizon, the EU Research and Innovation magazine\u003C\/a\u003E\u003C\/p\u003E\n \u003Cp\u003ESee our full republication guidelines \u003Ca href=\u0027\/horizon-magazine\/republish-our-stories\u0027\u003Ehere\u003C\/a\u003E\u003C\/p\u003E\n \u003Cp\u003EHTML for this article, including the attribution and page view counter, is below:\u003C\/p\u003E\u003Cdiv class=\u0022js-form-item form-item js-form-type-textarea form-item-body-content js-form-item-body-content ecl-form-group ecl-form-group--text-area form-no-label ecl-u-mv-m\u0022\u003E\n \n\u003Cdiv\u003E\n \u003Ctextarea data-drupal-selector=\u0022edit-body-content\u0022 aria-describedby=\u0022edit-body-content--description\u0022 id=\u0022edit-body-content\u0022 name=\u0022body_content\u0022 rows=\u00225\u0022 cols=\u002260\u0022 class=\u0022form-textarea ecl-text-area\u0022\u003E\u003Ch2\u003ECRISPR provides hope of sickle cell cure\u003C\/h2\u003E\u003Cp\u003EEarlier this decade, geneticists found that they could easily reprogramme bacterial immune machinery to create a gene editing tool that is able to search for genes in plant and animal cells. They could also manipulate the enzyme called Cas9 used in bacteria in order to insert new DNA into genes.\u003C\/p\u003E\u003Cp\u003EThe CRISPR-Cas9 gene editing technique was born and what was months of lab work to edit genes turned to days, if not hours.\u003C\/p\u003E\u003Cp\u003E\u2018Essentially, the potential of gene editing was already there. Of course, it was much more challenging,\u2019 said Professor Luigi Naldini of the San Raffaele Telethon Institute for Gene Therapy in Milan, Italy.\u003C\/p\u003E\u003Cp\u003E\u2018People call it the \u2018BC\u2019 era \u2013 Before CRISPR.\u2019\u003C\/p\u003E\u003Cp\u003ESince then, speculation has been rife about the potential applications of quick and easy gene editing. Apart from promises of sterile mosquitos and disease-resistant bananas, there were claims that CRISPR could delete disease-causing genes, or add in \u2018healthier\u2019 versions.\u003C\/p\u003E\u003Cp\u003E\u003Cstrong\u003ESickle cell\u003C\/strong\u003E\u003C\/p\u003E\u003Cp\u003EAt the Institut Imagine in Paris, France, scientists are using CRISPR to see if they can cure a genetic disorder known as sickle cell disease.\u003C\/p\u003E\u003Cp\u003EIn sickle cell disease, stem cells in the bone marrow can suffer a mutation in the gene responsible for haemoglobin, the protein in blood that carries oxygen. The result is withered, hardened red blood cells that carry oxygen poorly.\u003C\/p\u003E\u003Cp\u003E\u2018In our project, we\u2019re using CRISPR-Cas9 technology to produce deletions in the patient\u0027s genome,\u2019 explained Dr Tristan Felix, whose laboratory is part of the \u003Ca href=\u0022https:\/\/cordis.europa.eu\/project\/rcn\/207274\/en\u0022 target=\u0022_blank\u0022 rel=\u0022noopener noreferrer\u0022\u003EGENE FOR CURE\u003C\/a\u003E project, led by Professor Marina Cavazzana, based at the institute.\u003C\/p\u003E\u003Cp\u003EThe process involves taking stem cells from a patient\u2019s own body, treating the faulty genes with CRISPR-Cas9, and then reinserting the altered stem cells into the body to alleviate the symptoms of a genetic disease.\u0026nbsp;\u003C\/p\u003E\u003Cp\u003EDr Felix\u2019s research uses CRISPR-treated stem cells to restart making foetal haemoglobin, the oxygen-carrying protein in red blood cells. While it\u2019s usually made when a child is in the womb, it offers a good substitute for adult haemoglobin.\u003C\/p\u003E\u003Cp\u003ETheir treatment involves CRISPR entering the cell to mimic a rare deletion in the genome that blocks the genetic \u2018off switch\u2019 for foetal haemoglobin, allowing it to be produced again. After being returned to the bone marrow, these stem cells begin to make normal red blood cells, now with foetal haemoglobin.\u003C\/p\u003E\u003Cp\u003EThe treatment is currently in animal trials and Dr Felix believes it could work well in parallel with other sickle cell medicines. \u2018These two weapons could really allow patients to not have a sickle disease anymore and lead a normal life.\u2019\u003C\/p\u003E\u003Cp\u003EReturning the stem cells to the bone marrow into patients still has surgical risks, and requires long post-surgery stays in hospital with no guarantee as yet of long-term success.\u003C\/p\u003E\u003Cp\u003EHowever, using CRISPR on a patient\u2019s own stem cells means it avoids running into problems with their immune system. \u2018Since we are grafting in the cells of the patient, the risk is very low,\u2019 said Dr Felix.\u003C\/p\u003E\u003Cp\u003EImmune response is one of the major barriers for scientists who want to deliver CRISPR-based treatments into patients\u2019 cells. These \u2018gene therapies\u2019 can be used to treat cells in a lab, or directly in the patient\u2019s body.\u003C\/p\u003E\u003Cp\u003E\u2018We have to work out the biological and immune barriers,\u2019 said Prof. Naldini, who is working to improve the safety and precision of future CRISPR-based medicine as part of a transatlantic project called \u003Ca href=\u0022https:\/\/cordis.europa.eu\/project\/rcn\/219838\/en\u0022 target=\u0022_blank\u0022 rel=\u0022noopener noreferrer\u0022\u003EUPGRADE\u003C\/a\u003E. \u2018I would consider immunology to be the main barrier overall.\u2019\u003C\/p\u003E\u003Cp\u003E\u003Cstrong\u003EVirus\u003C\/strong\u003E\u003C\/p\u003E\u003Cp\u003EThe most common way to deliver CRISPR is to stuff it into a non-harmful virus, which then makes its way to the desired cells.\u003C\/p\u003E\u003Cp\u003EHowever, the body\u2019s immune reaction to viruses means CRISPR may never get to the intended site.\u003C\/p\u003E\u003Cp\u003EChanging the virus\u2019s characteristics can solve the problem, says Prof. Naldini. Another way is to find an alternative chemical chauffeur. \u2018We are essentially looking at that - using nano particles made by different combinations of polymers, lipids and sugars.\u2019\u003C\/p\u003E\u003Cp\u003EThe project is tackling the doubts that some scientists have about CRISPR\u2019s machinery. One worry is that poor CRISPR accuracy could affect \u2018off-target\u2019 parts of the genome. Another is that inserting one new gene could disrupt another already in the genome.\u003C\/p\u003E\u003Cp\u003EProf. Naldini wants to perfect the CRISPR tool by improving its cutting\/inserting accuracy.\u003C\/p\u003E\u003Cp\u003E\u003Cblockquote class=\u0022tw-text-center tw-text-blue tw-font-bold tw-text-2xl lg:tw-w-1\/2 tw-border-2 tw-border-blue tw-p-12 tw-my-8 lg:tw-m-12 lg:tw--ml-16 tw-float-left\u0022\u003E\n \u003Cspan class=\u0022tw-text-5xl tw-rotate-180\u0022\u003E\u201c\u003C\/span\u003E\n \u003Cp class=\u0022tw-font-serif tw-italic\u0022\u003E\u2018I would consider immunology to be the main barrier overall.\u2019\u003C\/p\u003E\n \u003Cfooter\u003E\n \u003Ccite class=\u0022tw-not-italic tw-font-normal tw-text-sm tw-text-black\u0022\u003EProf. Luigi Naldini, San Raffaele Telethon Institute for Gene Therapy, Italy\u003C\/cite\u003E\n \u003C\/footer\u003E\n\u003C\/blockquote\u003E\n\u003C\/p\u003E\u003Cp\u003EThe most common cutting enzyme in CRISPR is called Cas9, originally found in a type of bacteria. By gently directing that bacteria\u2019s evolution in the lab, his team hope to create a version of Cas9 that is more suited to work on human DNA.\u003C\/p\u003E\u003Cp\u003EResearchers could also switch out Cas9 for a molecule called recombinase, which adds genetic sequences instead of cutting them out. They too will be evolved to match the desired genetic code.\u0026nbsp;\u003C\/p\u003E\u003Cp\u003EOther methods Prof. Naldini\u2019s team are researching include seeing how CRISPR can \u2018switch\u2019 genes on and off and insert new genes more efficiently.\u003C\/p\u003E\u003Cp\u003E\u0027We would hopefully test some of these at the end of the project and be ready to start trials,\u0027 said Prof. Naldini.\u003C\/p\u003E\u003Cp\u003E\u003Cstrong\u003EConvenience\u003C\/strong\u003E\u003C\/p\u003E\u003Cp\u003EOverall, Prof. Naldini sees CRISPR as a convenience, but not a panacea. \u2018It\u2019s not a big difference from what we had before,\u2019 he said. \u2018All the biological barriers and immunological barriers (for gene therapy) are still there.\u2019\u003C\/p\u003E\u003Cp\u003ENonetheless the potential for CRISPR to work alongside existing gene therapies gives Dr Felix hope. He expects a cure for sickle cell diseases to be found within the next ten years.\u0026nbsp;\u003C\/p\u003E\u003Cp\u003E\u2018I\u2019m still quite optimistic, but the bottleneck will be for safety,\u2019 he said. \u2018Most of our time and money will be spent making sure that these treatments are safe and efficient.\u2019\u003C\/p\u003E\u003Cp\u003E\u003Cem\u003EThe research in this article was funded by the EU. 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