上集提及自90年代起,科學家便開始著手研究利用mRNA的方式試圖在老鼠身上製造對應的蛋白質。站在免疫細胞的角度來看,外來的mRNA終歸是外來之物,並非身體自然產生形成,故此必須鏟除。711Please respect copyright.PENANAPyNgZBA0gb711Please respect copyright.PENANAM7JlQrjlek
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而在消滅外物的過程中,一系列的免疫反應亦將會啟動。正因如此,若然想將此mRNA技術套用在人類身上的話,科學家必須想辦法使外來的mRNA免受免疫細胞消滅,同時亦需壓抑免疫反應的產生。711Please respect copyright.PENANAUSDO6caFgm
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這樣才能使mRNA能順利進入預想的目的地(身體細胞) ,以及減低對身體細胞不必要的負荷產生。711Please respect copyright.PENANApNNhEAQ2Mm
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(圖2)在科學家尋找辦法其間,他們受到一道非常重要的研究啟發。711Please respect copyright.PENANAEV6wZStehE711Please respect copyright.PENANAQRmdEIQTJ6
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對比哺乳動物的DNA,細菌的DNA在人體裡會產生更強烈的免疫反應。711Please respect copyright.PENANAEsL11NxKOQ
尋尋覓覓,科學家們發現,形成此現象的其中一因由是出於哺乳動物的DNA基因排組中,在C及G密集區域裡頻繁出現名為methylation的改造;711Please respect copyright.PENANAKj5REXwFZX
細菌的DNA並沒有頻繁出現這種改造,因此更容易觸發人體的免疫系統反應。711Please respect copyright.PENANAVK6hWtLCGY
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(圖3)其後,科學家們發現RNA跟DNA一樣,有著不同形形式式的改造,而個別的改造亦有著躲避免疫系統追捕的功能。711Please respect copyright.PENANAEL1znKb8As711Please respect copyright.PENANAfGjvjnxI96
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更甚的是,不同款式病毒的RNA,其改造結構的出現比普通細胞出現得更為頻繁且為獨特,這亦使科學家們更為堅信,改造mRNA的結構將可成為壓抑產生免疫反應的其中一手段。711Please respect copyright.PENANAo9rgGgm1QJ
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(圖4)積累多年來的研究成果,現時武肺輝瑞mRNA疫苗的mRNA正有著名為N1-methylpseudouridine (m1Ψ)的結構改造,這不但能大大減低我們體內對mRNA所產生的免疫系統反應,同時亦有助mRNA在我們細胞內產生武肺S蛋白質,繼而讓免疫系統辨認及製作對應的抗體。711Please respect copyright.PENANAm16FCptTSK
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Ref1:https://pubs.acs.org/doi/10.1021/acscentsci.1c00197711Please respect copyright.PENANAxklyumjJVW
Ref2:https://www.cell.com/immunity/fulltext/S1074-7613(05)00211-6711Please respect copyright.PENANAtqwOXpUxl8
Ref3:https://www.sciencedirect.com/science/article/abs/pii/S0168365915300948?via%3Dihub711Please respect copyright.PENANAZ6cjWzEAnj