Pigs that are resistant to a deadly viral disease have been created by scientists at Edinburgh’s Roslin Institute.
The gene-edited animals remained healthy when exposed to classical swine fever (CSF), a highly contagious and often fatal disease. The virus was eradicated in the UK in 1966, but there have been several outbreaks since and it continues to pose a major threat to pig farming worldwide.
“Classical swine fever is a devastating disease for livestock and farmers as we saw with the outbreak in the UK, 25 years ago,” said Helen Crooke, mammalian virology deputy leader at the Animal and Plant Health Agency (APHA), where the pig trial was performed. “Hopefully this breakthrough can help bolster the resilience of the livestock sector to the disease.”
Photo: AFP 照片:法新社
CSF, also known as hog cholera or pig plague, causes fever, skin lesions, convulsions, diarrhea — and often death within 15 days.
In the UK, periodic outbreaks since the 1960s have led to the culling of 75,000 pigs. In countries such as China, Russia and Brazil, where the disease is endemic, CSF is controlled through costly and labor-intensive vaccination programs and international trade restrictions.
Christine Tait-Burkard, a group leader at the Roslin Institute, said: “This virus has a severe effect on animal welfare and productivity.”
Photo courtesy of Ministry of Agriculture 照片:農業部提供
The latest study, the first to demonstrate resistance through gene editing, targeted a gene responsible for producing a protein called DNAJC14. This protein had been shown to play a critical role in the replication of pestiviruses (the virus family that includes CSF) once they enter the cell. Previous studies in cells had found that altering just a few letters of the DNA code blocked viral replication.
In the latest study, scientists at the Roslin Institute created a line of pigs with the same precise edits to their DNA. Four of the pigs were then exposed to CSF, along with four control pigs, at APHA’s biosecure facility.
A week after inoculation, the control animals were showing symptoms of the disease and had high levels of the virus in their blood. By contrast, the gene-edited pigs were completely healthy and showed no signs of infection. Several generations of gene-edited pigs were monitored and no adverse effects on health or fertility were observed.
Photo: AFP 照片:法新社
The same gene is involved in the replication of pestiviruses that infect cattle and sheep — less severe diseases, but ones that continue to circulate in the UK — and the team is now investigating whether the same edit confers resistance for these species.
The advance comes as many countries are relaxing rules around gene editing in agriculture, with the UK’s Precision Breeding Act paving the way for gene-edited crops. Countries including the US, Japan and Brazil have already approved gene-edited livestock. Based on previous work at Roslin, Genus, a company based in Basingstoke, has generated pigs that are resistant to a virus that causes porcine reproductive and respiratory syndrome, which have been approved for sale in the US and are expected to go on the market there next year.
Simon Lillico, research scientist at the Roslin Institute and a co-author, said: “In my mind there is a moral imperative that if we can make animals that are disease resistant, then we probably should.”
Emily Clark, of EMBL’s European Bioinformatics Institute, who was not involved in the research, said: “Decades of genomic research have made it possible to pinpoint and precisely edit the genes involved in disease resistance. Research like this is helping to create healthier animals, reduce losses for farmers in areas affected by swine fever, and marks a major step forward in using genomics-enabled innovation to build resilience to disease in livestock populations.”
The findings are published in the journal Trends in Biotechnology.
(The Guardian)
愛丁堡羅斯林研究所的科學家成功利用基因編輯技術,培育出能抵抗一種致命病毒性疾病的豬隻。
這些經過基因編輯的動物在暴露於豬瘟(classical swine dever, CSF)病毒後仍然健康。豬瘟是一種具高度傳染性,且常致命的疾病。在英國,豬瘟病毒已在1966年被撲滅,但此後仍多次爆發,持續對全球養豬業構成重大威脅。
「豬瘟對畜牧業與農民來說是毀滅性的疾病,我們在25年前英國的疫情中就見識過它的影響」,英國動植物健康局(Animal and Plant Health Agency, APHA)哺乳動物病毒學副主管海倫·克魯克表示。該機構負責進行此次豬隻試驗。「希望這項突破能夠強化畜牧業對豬瘟的防禦能力」。
豬瘟,又稱為「豬霍亂」或「豬瘟疫」,會引起發燒、皮膚病變、抽搐、腹瀉等症狀——通常在15天內就會導致死亡。
英國自1960年代以來的幾次疫情,已造成七萬五千頭豬被撲殺。而在中國、俄羅斯與巴西等病毒長期存在的國家,防疫主要依賴成本高昂且勞力密集的疫苗接種計畫及國際貿易限制。
羅斯林研究所研究團隊主持人克莉絲汀·塔特-柏卡德博士指出:「這種病毒對動物福利與生產力的影響極為嚴重」。
這項最新研究是首度透過基因編輯展現抗病性的實例,目標鎖定一個負責產生名為NAJC14蛋白質的基因。先前的研究顯示,該蛋白質在瘟病毒屬(pestivirus,包含豬瘟病毒)進入細胞後的複製過程中扮演關鍵角色。過去的細胞實驗發現,只要改變 DNA序列中的幾個字母,就能阻斷病毒的複製。
在這項研究中,羅斯林研究所的科學家培育出一群豬,在其DNA中做出相同的精確編輯。之後,四頭經基因編輯的豬,以及四頭未經基因編輯的對照組豬隻,同時在英國動植物健康局的高安全實驗設施中接觸豬瘟病毒。
接種後一週,對照組豬隻出現明顯症狀,血液中的病毒量也相當高;相對地,基因編輯豬則完全健康,沒有任何感染跡象。研究人員觀察了多代基因編輯豬,並未發現其健康或生育能力受到不良影響。
該基因同樣也在牛與羊感染的瘟病毒複製過程中扮演了角色——雖然這些疾病較不嚴重,但仍在英國持續流行。研究團隊目前正調查相同的基因編輯是否能讓這些物種擁有抗病能力。
這項進展正值多國逐步放寬農業基因編輯相關法規之際。英國的《精準育種法案》(Precision Breeding Act)已為基因編輯農作物鋪路。美國、日本與巴西等國也已批准基因編輯家畜。根據羅斯林研究所早期的研究成果,位於英國貝辛斯托克的動物遺傳學公司Genus已培育出能抵抗「豬繁殖與呼吸症候群病毒」(PRRSV)的豬,已獲美國批准,預計於明年上市。
羅斯林研究所研究員暨論文共同作者賽門·李利可博士表示:「在我看來,若我們有能力讓動物具備抗病能力,在道德上我們就應該這麼做」。
未參與此研究的歐洲分子生物學實驗室生物資訊研究所(EMBL-EB)艾蜜莉·克拉克博士則指出:「數十年的基因體研究讓我們能夠精確找出並編輯與抗病性相關的基因。這類研究有助於培育更健康的動物、減少豬瘟流行地區的農民損失,是利用基因體創新技術強化家畜抗病能力的重要里程碑」。
該研究成果已發表於《生物科技趨勢》(Trends in Biotechnology)期刊。
(台北時報林俐凱編譯)
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