CNN, October 17th 2017
Researchers in Japan may have found a way to produce cheaper drugs that could be used to treat a range of diseases from chicken eggs.
They have successfully genetically modified hens to produce eggs containing large amounts of interferon beta protein, a protein used to treat various illnesses, including multiple sclerosis and cancer.
The protein is very expensive, costing between $300-$1000 for just one microgram, according to pharmaceutical company, Cosmo Bio who co-led the research.
For treating MS, for example, the interferon dosage can start at 30 micrograms and increase from there.
The research was jointly conducted by scientists from the National Institute of Advanced Industrial Science and Technology (AIST), the National Agriculture and Food Research Organization and Cosmo Bio.
According to Mika Kitahara, a spokesperson for Cosmo Bio, this technology will reduce the price of cancer drugs at least by 90% if proven successful in further trials.
The conventional production of interferon needs large aseptic (sterile) facilities, but eggs work as a protein-producing aseptic system, said Kitahara.
Isao Oishi, chief researcher from the cell and molecule mechanism research group at AIST said the research was conducted to test whether the eggs from genetically modified chickens can be used for cheap production of these proteins.
A range of biological systems can be used to try and create drugs, such as bacteria, yeast and some mammalian cells, but “some proteins just don’t suit these systems,” said Professor Helen Sang from the Roslin Institute at the University of Edinburgh in the UK. For those that don’t quite work, “making protein from egg-white is relatively easy,” she told CNN.
“Interferon was discovered as a cell-signaling protein molecule in the body which acts against viruses,” said Dr. Robert Bermel, director of the Mellen Center for Multiple Sclerosis at the Cleveland Clinic Neurological Institute. Later it was used to treat auto-immune diseases — where a person’s immune system attacks their body — like multiple sclerosis, he adds.
Multiple Sclerosis (MS) affects the brain, spinal cord and eyes, resulting in a range of symptoms, such as vision problems, numbness and difficulties walking.
Bermel explained that interferon protein molecule is expensive because manufacturing it is a tedious process requiring strict quality control.
“Interferon for MS can be manufactured from bacteria like insulin or from Chinese hamster ovary cells.” The quantity of interferon produced this way, however, is very little. “(The new research) sounds like a relatively inexpensive way to mass produce it,” he says.
Previously, the Japanese scientists tried to produce the modified protein by inserting the required genes into chicken chromosomes using a virus as a vector, but said this produced an “irregular result.” The new method aims to more accurately and stably produce the protein by knocking in edited genes, using a gene-editing tool called CRISPR. The researchers are currently writing up their findings for academic publication.
More research is needed and the interferon beta protein will need safety clearance through trials before it can be used to treat patients.
However, Sang explained it’s not as simple as modifying these chickens to get endless supplies of the drug at a lower cost.
“You’ll have to show (the drug) is exactly the same as the drugs that have gone through all the clinical trials,” said Sang, whose own team has been working on transgenic chickens for over a decade. As well as simply making the drugs in the eggs, they will also need to be purified and validated through additional research, she said.
If this new source of interferon is shown to be the same, structurally, “then there is a lot of advantage in terms of scale,” said Sang. You can start with a few hens then scale up quickly, she said.
One drug, Kanuma, produced using modified chickens has already been approved by the US Food and Drug Administration to treat Lysosomal Acid Lipase Deficiency, a rare inherited condition where the body does not produce enough of a protein that helps the body break down fatty material.
The immediate hope is for the cancer-battling medicine to result in affordable medical products. The team is looking forward as well, with research underway to produce human antibodies using the same method.
2017.10.17，CNN報導
日本的研究人員可能已經找到了一種生產便宜藥物的方法，那就是從雞蛋中生產可以治療一系列疾病的藥物。他們成功使基因改造的母雞產生含有大量干擾素β蛋白的雞蛋。干擾素β蛋白是一種可以用於治療各種疾病的蛋白質，包括多發性硬化症和癌症。
共同領導這項研究計畫的製藥公司Cosmo Bio表示，這種蛋白質非常昂貴，一微克的價錢就需要300到1000美元。而如果是治療多發性硬化症，干擾素劑量的使用至少需要30微克或是更多。
這項研究是由日本產業技術綜合研究所（AIST），日本農業和食品產業技術研究機構和Cosmo Bio的科學家共同進行。
據Cosmo Bio發言人Mika Kitahara表示，如果這項技術能在進一步試驗中取得成功，該技術可望能大幅降低癌症藥物費用至現在的一成以下。Mika也提到:「干擾素的常規生產需要大的無菌設施，但是蛋可以作為生產蛋白質的天然無菌系統」。
AIST細胞和分子機轉研究小組首席研究員Isao Oishi表示他們正在測試基因改造母雞所產生的雞蛋是否能作為更經濟實惠的方式來生產蛋白質。
英國愛丁堡大學Roslin研究所的Helen Sang教授表示，「為數不少的生物系統都可用於嘗試和製造藥物，如細菌、酵母菌和一些哺乳動物細胞，但有些蛋白質則不適用於這些系統，而那些蛋白質如果從蛋白製造會相對比較容易一些。」
位於克里夫蘭神經病學研究所，研究多發性硬化症的Mellen中心主任Robert Bermel博士說：「干擾素被發現為身體中的細胞信號蛋白分子，用於對抗病毒。」他補充說道:「之後它被用來治療自體免疫疾病，這種疾病是一個人的免疫系統會攻擊自己的身體，像多發性硬化症。」
多發性硬化症（MS）會影響腦、脊髓和眼睛，導致一系列症狀，如視力問題、麻木和步行困難。
干擾素蛋白分子是相當昂貴的，因為製造過程很繁瑣，需要嚴格的品質控制。Bermel表示「干擾素可以像胰島素一樣用細菌或者由倉鼠卵巢細胞製成。然而，以上述方式產生的干擾素量很少。而用雞蛋製造干擾素聽起來像是一種相對便宜的大規模生產方式。」
以前日本科學家試圖通過使用病毒作為載體將需要的基因插入到雞染色體中來產生修飾的蛋白質，但是會產生不穩定的結果。新方法則使用稱為CRISPR的基因編輯工具插入編輯的基因來更準確且穩定的產生蛋白質。研究人員正透過學術期刊來發表出他們的研究成果。
現在，干擾素β蛋白仍需要通過更多安全性的檢查以及研究來確保可以用於治療患者。
然而這項計畫不單單只是透過改造雞隻的基因來獲得無限的便宜藥物來源如此簡單。據已帶領團隊研究基因轉殖雞有十多年的Sang表示「你必須證明這種雞蛋產生的藥物與你之前經過臨床試驗的藥物是完全一樣的。除了製作雞蛋中的藥物外，還需要通過額外的研究進行純化和驗證。如果這種新來源產生的干擾素在結構上是可以保持一致的，那麼在生產規模上就能有很大的優勢。可以從幾隻母雞開始，然後迅速擴大產藥規模。」
美國食品和藥物管理局目前已有核准一種使用基因改造雞生產的藥物Kanuma用於治療伍爾曼氏症。這是一種罕見的遺傳性病症，其特徵為身體不能產生足夠的蛋白質來分解脂肪物質。 除了希望癌症藥物可以成為大家能負擔的藥物，該研究團隊也期待這項方法未來也可以用於人類抗體的生產。
