草泥馬除了外貌相當奇特之外,牠們身體的免疫系統亦非常特別,當中獨特之處更被科學家採用來醫治疾病。803Please respect copyright.PENANA0MGTMbiCGB
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(圖1)草泥馬及駱駝科生物的免疫系統,不但只能夠產生人類常見的抗體(Antibody),亦能夠產生一種人類或其他動物無法產生的細小抗體,1993年被首先在駱駝身上發現(Ref1),統稱為Heavy chain-only antibody。803Please respect copyright.PENANAirOOwU6nJL
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而這些Heavy chain-only antibody中,有某一部份的形狀將主宰抗體將會針對的目標,科學界將佢稱之為Single domain antibody,又或者叫VHH,又或者叫Nanobody;803Please respect copyright.PENANAAY4ASNSllL
為方便討論,下文一律稱之為Nanobody。803Please respect copyright.PENANA4PfUYIsaU7
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題外話,鯊魚亦能產生類近的抗體,但對比羊泥馬駱駝等,鯊魚明顯比較難於管理及飼養,所以相關的研究均側重在駱駝科生物。803Please respect copyright.PENANA85GVcb7v2o
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Nanobody出奇地耐熱,有時候更可以抵受高達90度高溫仍能運作,而且大概是體積實在太過細少及擁有與人類頗為相似的區域關係,Nanobody並不會觸發人類的免疫系統。803Please respect copyright.PENANA4cKfonnTPr
同時,最最為有趣的是,它能夠抵禦口水裡的酵素襲擊,大有潛力可以成為口服藥物。803Please respect copyright.PENANAnEGP7IElqC
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(圖2)體積細小的抗體,意味著能夠到達更鬼祟深入的地方,到達人類抗體無法前往的區域。因此,有科學家偷龍轉鳳,借助草泥馬製造Nanobody,加以改良適合人體使用,最終更成為研發在2019年被FDA認司的藥物Caplacizumab。803Please respect copyright.PENANAnSlqepRtGJ
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Caplacizumab由Ablax公司研發,但最終被Sanofi公司在2018年收購。無論如何,這隻藥物能夠醫治一種名為 acquired thrombotic thrombocytopenic purpura(aTTP)的頑疾,病徵為血小板不斷促使血液凝固,導致血液無法輸送各個器官。803Please respect copyright.PENANAM1EgxzasNU
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Caplacizumab因為體積細小的關係,能有效阻隔血小板跟另一蛋白質的互動,因而能夠杜絕血小板無故地凝結血液的發生。803Please respect copyright.PENANAMvlAhHBany
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而在Caplacizumab未研發之前,普遍的處理手法就只有是輸血或用上類固醇,但有好大機會產生長遠副作用,而用上Caplacizumab則能避免不良副作用發生。803Please respect copyright.PENANA1co9fvRlgd
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(圖3)近日,有科學家更嘗試利用Nanobody醫治武肺(Ref2),他們將武肺病毒與人體細胞接觸的位置(S protein)打入駱駝身體裡頭,成功拿取對應338種Nanobody。803Please respect copyright.PENANAgIB1VgTHJn
他們再進行一系列的研究,從338種中找出2種能夠應對各武肺變種病毒的Nanobody(可惜的是,他們並沒有測試現今大流行的D614G變種病毒),證實Nanobody可以阻隔武肺病毒進入細胞。803Please respect copyright.PENANADMYc4yfl3D
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「題外話,如果你並不知道S protein是甚麼東東,可到我所寫的另一篇文章了解一下:https://www.penana.com/story/66244/%E7%A7%91%E6%99%AE%E5%B0%88%E6%AC%84-%E8%96%AF%E4%B8%8D%E6%8F%80%E5%96%AE/issue/9」803Please respect copyright.PENANAvCg8vSKi5h
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他們已成功利用細菌作為載體,找出大量製造這兩款Nanobody的辦法。803Please respect copyright.PENANAAGG83zpCga
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雖然他們暫時還沒有進行動物研究,但基於Nanobody細小及有口服的功能,他們提出將Nanobody以霧化劑的方式推出市場,更不排除可能有口服的功能。803Please respect copyright.PENANAZPI3qoOx27
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這個想法看起上來有點妙想天開,希望到時成功啦吓!803Please respect copyright.PENANAvXZd9Tubmg
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不過要注意的是,Nanobody並不是沒有缺點的。803Please respect copyright.PENANAt1Nit9Yapv
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一、它們的體積非常細小關係,就算將自己以倍數乘三的方式黏在一起,同樣會被迅速腎臟過濾排出體外,滯留在循環系統的時間大概只有兩三小時,無法帶來長久效果。803Please respect copyright.PENANAOzqEfPAmOP
(相比之下,普遍的抗體則可以逗留在循環系統二至三星期有多)803Please respect copyright.PENANASMT2XzZvkC
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二、它們缺乏普遍抗體與免疫細胞相認的部份(簡稱為Fc),亦即是代表它們難以有效召叫免疫細胞前來殺滅病毒,純粹只有計阻止病毒入侵細胞的功能。803Please respect copyright.PENANAGgFBdgwr12
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上述兩點,解決辦法非常簡單,就是將Fc部份裝配在Nanobody身上。803Please respect copyright.PENANAYaBTjHKqZe
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但問題是,將額外配件裝上Nanobody的話,只是有點本末倒置,將Nanobody體積細小的優點破壞。803Please respect copyright.PENANAg9eqnSkV6C
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下一篇的深入淺出,將會進一步對抗體進行講解(譬如文中所說的Fc究竟是甚麼東東),以及講述抗體有機會帶來的副作用等等。803Please respect copyright.PENANAIAY6isR3mN
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如果想我快啲出文的話,請入去Penana網站科普專欄–薯不揀單俾一個like以及Bookmark,這對我非常之重要。803Please respect copyright.PENANAJ1aK3ViKxn
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Link: https://www.penana.com/story/66244/%E7%A7%91%E6%99%AE%E5%B0%88%E6%AC%84-%E8%96%AF%E4%B8%8D%E6%8F%80%E5%96%AE/toc803Please respect copyright.PENANAm3qmyUF6mf
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同時亦可以在Penana網站裡按「買一嚿薯仔」,以課金的方式推動我繼續搜羅資料寫文,多謝。803Please respect copyright.PENANAEMGukicEyl
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Link:803Please respect copyright.PENANAWI4WZ86q0D
https://www.penana.com/user/27349/%E8%96%AF%E4%BB%94%E8%81%9E%E8%8C%B1%E8%8E%89/portfolio803Please respect copyright.PENANAymW4PKKJzQ
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有興趣接收科普資訊的話,歡迎follow IG: potatopigtongue。803Please respect copyright.PENANA5bFhf6m7Yd
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Ref1: https://pubmed.ncbi.nlm.nih.gov/8502296/803Please respect copyright.PENANACUFPAQnbdk
Ref2:https://www.biorxiv.org/content/10.1101/2020.08.09.242867v1.full.pdf