[{"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\/7172\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\u003EGenetically engineered animals offer fresh hope to heart valve patients\u003C\/h2\u003E\u003Cp\u003EEvery year, about 300,000 people worldwide receive a new heart valve. Whenever possible, doctors use valves made of tissue from cows or pigs, because the synthetic alternatives can cause blood clots.\u003C\/p\u003E\u003Cp\u003EBut there is a hitch. Although animal tissue valves can last up to 30 years in people over 60 years old, they can be destroyed in just five years in a younger person, probably because of their more aggressive immune system.\u003C\/p\u003E\u003Cp\u003EEnter the genetically engineered bull.\u003C\/p\u003E\u003Cp\u003EScientists used CRISPR gene editing technology to create two bovine mutations that should lessen people\u2019s immune responses to the animal tissue.\u003C\/p\u003E\u003Cp\u003EThe mutations knock out two sugars which coat the bull\u2019s cells but are not found in humans: \u03b1-Gal and Neu5Gc.\u003C\/p\u003E\u003Cp\u003E\u2018The objective is to have animals that express tissues that are less foreign to the human body,\u2019 said Dr Emanuele Cozzi, coordinator of a project called \u003Ca href=\u0022https:\/\/cordis.europa.eu\/project\/rcn\/110147\/factsheet\/en\u0022 target=\u0022_blank\u0022 rel=\u0022noopener noreferrer\u0022\u003ETRANSLINK\u003C\/a\u003E, which has been trying to improve the long-term success of heart valve replacements.\u0026nbsp;\u003C\/p\u003E\u003Cp\u003EIn theory this means people\u2019s immune systems will be less likely to attack the animal tissue, added Dr Cozzi, who is director of the Transplant Immunology Unit at Padua University Hospital in Italy.\u003C\/p\u003E\u003Cp\u003E\u003Cstrong\u003EClone\u003C\/strong\u003E\u003C\/p\u003E\u003Cp\u003EAs part the project, an Italian company, \u003Ca href=\u0022https:\/\/www.avantea.it\/en\/\u0022 target=\u0022_blank\u0022 rel=\u0022noopener noreferrer\u0022\u003EAvantea\u003C\/a\u003E, created bovine cells with the two mutations and used them to clone a bull with a technique similar to the one that produced \u003Ca href=\u0022https:\/\/dolly.roslin.ed.ac.uk\/facts\/the-life-of-dolly\/index.html\u0022 target=\u0022_blank\u0022 rel=\u0022noopener noreferrer\u0022\u003EDolly the sheep\u003C\/a\u003E.\u003C\/p\u003E\u003Cp\u003E\u2018We are the first to make cattle (with these) mutations,\u2019 said Professor Cesare Galli, co-founder of Avantea.\u003C\/p\u003E\u003Cp\u003E\u2018The cloning step is required \u2026 to make the founder animals. Then they can breed normally,\u2019 said Prof. Galli.\u003C\/p\u003E\u003Cp\u003EAvantea had created the same mutations in pig cells using a technology called Transcription activator-like effector nucleases (TALEN) to edit the DNA, before CRISPR was available.\u003C\/p\u003E\u003Cp\u003E\u2018With CRISPR it is much easier to prepare the reagents that are needed to implement the system,\u2019 said Prof. Galli.\u003C\/p\u003E\u003Cp\u003EThat makes CRISPR cheaper because the reagents can be prepared in-house. However, in theory at least, it is less accurate, he added. \u003Cstrong\u003E\u2018\u003C\/strong\u003EBeing less precise in recognising the sequence to cut, there is the risk of undesired cuts - this is a risk that has yet to be quantified.\u2019\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\u0026#039;The animals we generated could have a potential application for food consumption, at least for people who do not tolerate red meat.\u0026#039;\u003C\/p\u003E\n \u003Cfooter\u003E\n \u003Ccite class=\u0022tw-not-italic tw-font-normal tw-text-sm tw-text-black\u0022\u003EProfessor Cesare Galli, co-founder, Avantea, Italy\u003C\/cite\u003E\n \u003C\/footer\u003E\n\u003C\/blockquote\u003E\n\u003C\/p\u003E\u003Cp\u003E\u003Cstrong\u003EQuality of life\u003C\/strong\u003E\u003C\/p\u003E\u003Cp\u003EAbout 100,000 people a year are given synthetic heart valves because they are too young to receive the animal tissue version.\u003C\/p\u003E\u003Cp\u003EBut these valves can lead to dangerous blood clots forming, so patients have to live on anticoagulants that impose \u2018severe limitations\u2019 on a young person\u2019s life, says\u0026nbsp;Dr Cozzi.\u003C\/p\u003E\u003Cp\u003EPeople have to avoid competitive sports and jobs with a high risk of injury, like construction or some police work.\u003C\/p\u003E\u003Cp\u003E\u2018If an accident occurs while on duty (they) may bleed to death,\u2019 said Dr Cozzi.\u003C\/p\u003E\u003Cp\u003EAlthough preliminary data suggests that people\u2019s immune systems attack valve transplants in response to the animal tissue used, scientists need more solid evidence of this before they can recommend using the genetically engineered animal tissue, says Dr Cozzi.\u003C\/p\u003E\u003Cp\u003EOther factors \u2013 including someone\u2019s blood pressure \u2013 cannot yet be ruled out as affecting the valve\u2019s lifespan, he says.\u0026nbsp;\u003C\/p\u003E\u003Cp\u003ETo understand more, TRANSLINK is carrying out a study of 1,600 cardiac patients \u2013 the largest of its kind \u2013 to compare their immune responses to animal or synthetic valve transplants or other types of surgery. The results are expected next year.\u003C\/p\u003E\u003Cp\u003EIf the study \u2018shows convincingly\u2019 that immunology is behind the premature failure of animal-derived heart valves, it should not be too difficult to find potential investors who could bring the genetically engineered tissue valves to market, says Dr Cozzi.\u003C\/p\u003E\u003Cp\u003E\u2018My hope would be that, based on the data of our study, we may change the outlook of young patients \u2026 (and offer them) a better quality of life.\u2019\u003C\/p\u003E\u003Cp\u003EThe mutations in both pigs and cows may pave the way for people to receive transplants of whole animal organs, Dr Cozzi says.\u003C\/p\u003E\u003Cp\u003E\u003Cstrong\u003ERed meat allergies\u003C\/strong\u003E\u003C\/p\u003E\u003Cp\u003EThe cloned animals may also benefit people allergic to red meat \u2013 a reaction which sometimes develops after they have been bitten by a tick.\u003C\/p\u003E\u003Cp\u003EScientists think the main culprit is the \u03b1-Gal sugar found in all animals other than primates.\u003C\/p\u003E\u003Cp\u003EAnything from a steak to collagen used in cosmetics can trigger a reaction, which can range from a skin rash to anaphylactic shock.\u003C\/p\u003E\u003Cp\u003E\u2018The animals we generated could have a potential application for food consumption, at least for people who do not tolerate red meat,\u2019 said Prof. Galli.\u003C\/p\u003E\u003Cp\u003ESome scientists in the US are also looking at possible links between the Neu5Gc sugar and cancer. The World Health Organization has classified red meat as \u003Ca href=\u0022https:\/\/www.who.int\/features\/qa\/cancer-red-meat\/en\/\u0022 target=\u0022_blank\u0022 rel=\u0022noopener noreferrer\u0022\u003Eprobably carcinogenic to humans\u003C\/a\u003E,\u0026nbsp;although there is limited evidence. \u0026nbsp;\u003C\/p\u003E\u003Cp\u003EMillions of years ago, humans developed a mutation that stopped the production of Neu5Gc and produced a slightly different sugar called Neu5Ac instead. The mutation made people resistant to malaria, and quickly spread across the population.\u003C\/p\u003E\u003Cp\u003EPigs, sheep, cows and most other mammals \u2013 with the exception of deer and some dogs - produce the Gc form which is \u2018highly antigenic\u2019 in humans, says Prof. Galli, meaning it prompts a strong immune response.\u003C\/p\u003E\u003Cp\u003EChicken and fish do not, which is one reason they are considered to be healthier to eat.\u003C\/p\u003E\u003Cp\u003EThe cloned cows could be a useful source of milk for baby food, as it would be closer to human milk because it does not carry the antigen, says Prof. Galli.\u003C\/p\u003E\u003Cp\u003EAvantea also plans to use CRISPR to create horses with the same mutations as the cows and pigs. Horse serum is used to make antidotes to snake bites, but it can trigger adverse reactions in some people. Knocking out \u03b1-Gal and Neu5Gc may prevent that, he says.\u003C\/p\u003E\u003Cp\u003EThe potential for the cloned pigs, cows and horses to improve people\u2019s health is huge. But for the time being, much of it is still theory, the scientists say.\u003C\/p\u003E\u003Cp\u003E\u2018We have the tools now, but there is work to be done to prove whether there is an advantage or not,\u2019 said Prof. Galli.\u003C\/p\u003E\u003Cp\u003E\u003Cem\u003EThe research in this article was funded by the EU. 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