科普專欄–薯不揀單 - 深入淺出–基因編輯技術的最新進展Prime Editing

現今已知接近有7萬幾種的基因變異會引起疾病。406Please respect copyright.ＰＥＮＡＮＡ5U6QHXaT8l
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隨著CRISPR基因編輯技術的興起，將會為根治這些疾病帶來曙光。406Please respect copyright.ＰＥＮＡＮＡnx5cyKidhk
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（圖2）圖中將展示「舊式」的編輯方法HDR（Homology Directed Repair)機制。406Please respect copyright.ＰＥＮＡＮＡdmbtvyo5NX
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sgRNA將會引領Cas9蛋白質抵達不理想的基因突變位置，其後Cas9蛋白質會將基因斬斷成兩截；406Please respect copyright.ＰＥＮＡＮＡZptIDxWM5o
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根據Cas9蛋白質的特性，可修改至只斬一條特定的DNA位置，其後會再提及。406Please respect copyright.ＰＥＮＡＮＡQs7mjIAygD
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（圖3）此時候，如果將盛載想修改的基因排組送到斷成兩截的基因附近，細胞便會加以利用，將原本的紫色區域改成為黃色區域。406Please respect copyright.ＰＥＮＡＮＡiqTapL9zlC
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但這個方法的隨機性非常之高，最終結果有可能會出現基因刪減，又或者是其他基因排組的插入。406Please respect copyright.ＰＥＮＡＮＡJwBrDRgLuj
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套用基因編輯技術於治療病人身上的話，精準度必須要非常之高，此手段明顯並不理想。406Please respect copyright.ＰＥＮＡＮＡqxa2pjHUBx
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（圖4）至於新式編輯方法Prime Editing方面，同樣亦是套用CRISPR技術，但各組件及理念則有所修改。406Please respect copyright.ＰＥＮＡＮＡCRAZNusZiH
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擁有Transcriptase Domain的Cas9變種蛋白質將會被含有預想修改基因排組的pegRNA引領到不理想的基因突變位置，而這一次只會斬斷特定的一條DNA。406Please respect copyright.ＰＥＮＡＮＡHXkNmRHrKp
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（圖5）其後，Cas9變種蛋白質會讀取pegRNA內含的預想修改基因排組，並將一條DNA的基因排組成功修改。406Please respect copyright.ＰＥＮＡＮＡwgQmHbnoEn
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經過一系列難以深入淺出的程序後，最終亦會完成成功修改雙方兩截的DNA。406Please respect copyright.ＰＥＮＡＮＡMDHy7peRsP
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（圖6）紅色區域為不理想的基因修改結果(Ref2)，新式編輯方法PrimeEditing明顯優勝於舊式編輯方法HDR，但仍有一定程度的進步空間。406Please respect copyright.ＰＥＮＡＮＡKw9cDZUNC5
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有朝一日，CRISPR基因編輯技術定必會在治療疾病上得以普及化。406Please respect copyright.ＰＥＮＡＮＡrgWrS6dqNc
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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。406Please respect copyright.ＰＥＮＡＮＡcrWaf5RW7Q
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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/toc406Please respect copyright.ＰＥＮＡＮＡhGzqHMVZv2
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https://www.penana.com/user/27349/%E8%96%AF%E4%BB%94%E8%81%9E%E8%8C%B1%E8%8E%89/portfolio406Please respect copyright.ＰＥＮＡＮＡZSxY4JCKvS
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Ref1:https://www.nature.com/articles/s41586-019-1711-4406Please respect copyright.ＰＥＮＡＮＡ3NPlLVd1pz
Ref2:https://www.nature.com/articles/s41467-020-19136-7