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。790Please respect copyright.PENANAl4hnLC5Zz5
790Please respect copyright.PENANAHq0ajEN9Jl790Please respect copyright.PENANAJThbYqN8Mq
790Please respect copyright.PENANAccm0hxengx
(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。790Please respect copyright.PENANAAl0m66Tww0
790Please respect copyright.PENANAhRL9cwScjY
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;790Please respect copyright.PENANAxLOFZGuKep
為方便討論,下文一律稱之為Nanobody。790Please respect copyright.PENANA1eW4cJT7E3
790Please respect copyright.PENANApXuuCNoIMQ
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。790Please respect copyright.PENANA8vkcrpAHjK
790Please respect copyright.PENANA4EnzUFcbnc
790Please respect copyright.PENANAR4Vv3Fdy0C
790Please respect copyright.PENANA10I6URp0Tk
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。790Please respect copyright.PENANAg4amu1i2hf
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。790Please respect copyright.PENANA2sPcEMMWK8
790Please respect copyright.PENANA1lDDC9Bs9D
790Please respect copyright.PENANABBw1P9xeVM
790Please respect copyright.PENANAH6XHJPwuV1
(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。790Please respect copyright.PENANAkqwBlRnOJp
790Please respect copyright.PENANAYX0vgkxejR
790Please respect copyright.PENANAZiWFAevLCV
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。790Please respect copyright.PENANA2nXuaBAF2A
790Please respect copyright.PENANAxzbqvKJYkc
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。790Please respect copyright.PENANAOIhqneyaDc
790Please respect copyright.PENANAOxI6bdwxzX
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。790Please respect copyright.PENANApOg9n4jryG
790Please respect copyright.PENANAAOjkvDz975
790Please respect copyright.PENANAOhSFLrariz
790Please respect copyright.PENANAmrhsZyvr12
(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。790Please respect copyright.PENANApin3O84r2t
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。790Please respect copyright.PENANAO2YTpsrkwW
790Please respect copyright.PENANACMz1BL183U
「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」790Please respect copyright.PENANA7GBcSdYxql
790Please respect copyright.PENANAZJer8kxu1Y
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。790Please respect copyright.PENANA2ZdAfGdgJF
790Please respect copyright.PENANAIJadMETZqk
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。790Please respect copyright.PENANA3ajM9vkVDG
790Please respect copyright.PENANAmvuySNlWyy
這個想法看起上來有點妙想天開,希望到時成功啦吓!790Please respect copyright.PENANA5sPz6HegXz
790Please respect copyright.PENANAutgHfVE1uS
不過要注意的是,Nanobody並不是沒有缺點的。790Please respect copyright.PENANAwhDNHwa8ec
790Please respect copyright.PENANAqDybXoP4nb
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。790Please respect copyright.PENANAxtWznx3PnB
(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)790Please respect copyright.PENANAoK0vTJ5rb9
790Please respect copyright.PENANAk0VcCU4gKP
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。790Please respect copyright.PENANAWmcAEo7KOc
790Please respect copyright.PENANAXtylXYpMLA
上述兩點,解決辦法非常簡單,就是將Fc部份裝配在Nanobody身上。790Please respect copyright.PENANA4RBxBKr8fM
790Please respect copyright.PENANAVVYPvjjsSO
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。790Please respect copyright.PENANA1GNOxVdtxL
790Please respect copyright.PENANAkbg3Ej570z
790Please respect copyright.PENANAS8rP7TV21L
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。790Please respect copyright.PENANAbupppkYo5U
790Please respect copyright.PENANAQEGDBEJVmR
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。790Please respect copyright.PENANArh121iY9oV
790Please respect copyright.PENANAtxM3MCvaCi
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/toc790Please respect copyright.PENANABADg8aRo7e
790Please respect copyright.PENANANDDoSaIFUJ
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。790Please respect copyright.PENANACRgz4knQNE
790Please respect copyright.PENANAUao76LoCZX
Link:790Please respect copyright.PENANAZ3oNWc3IQa
https://www.penana.com/user/27349/%E8%96%AF%E4%BB%94%E8%81%9E%E8%8C%B1%E8%8E%89/portfolio790Please respect copyright.PENANAN1WTc9t4LQ
790Please respect copyright.PENANACiM4aA44Wk
790Please respect copyright.PENANAuejaWKDXAI
有興趣接收科普資訊的話,歡迎follow IG: potatopigtongue。790Please respect copyright.PENANAzbHDU0zQ9w
790Please respect copyright.PENANAiuHfE1XptM
790Please respect copyright.PENANAiuhRaXmSsM
790Please respect copyright.PENANAKLoYlioEEC
790Please respect copyright.PENANAF6ar1VzRVG
Ref1: https://pubmed.ncbi.nlm.nih.gov/8502296/790Please respect copyright.PENANAg8fV9W8iyr
Ref2:https://www.biorxiv.org/content/10.1101/2020.08.09.242867v1.full.pdf