基因靜默

基因靜默（Gene silencing）又稱基因沈默、基因沈寂，泛指生物細胞藉各種基因表現調控（英語：Regulation of gene expression）機制抑制某一基因表現的現象^[1]^[2]，機制包括DNA甲基化、位置效應（英語：Position effect）、基因組銘印、基因轉應、重複序列誘導點突變^{[註 1]}^[3]、副突變、RNA靜默（英語：RNA silencing）（包括RNA干擾、基因壓制^{[註 2]}與非配對DNA介導的減數分裂沉默^{[註 3]}等^[4]，由miRNA、siRNA、piRNA與rasiRNA等小RNA引導）和mRNA降解等，例如許多mRNA的3'非轉譯區（3'UTR）即可和miRNA結合，以降低mRNA的轉譯達成基因靜默^[5]。

生物研究中，研究人員為研究一個基因的功能，會以RNA干擾或CRISPR等基因敲落技術達成基因靜默，大幅降低目標基因的表現以檢測其影響，進而推得目標基因的功能。相較於基因剔除完全移除目標基因的表現，基因敲落後目標基因表現雖被抑制，但仍保有一定程度的表現量^[6]。

臨床應用

名為 Givosiran 的藥物是針對δ-氨基酮戊酸合酶1（ALAS1，產生血基質的重要酶）的雙鏈siRNA，能特異性地降解 ALAS1 mRNA，產生基因靜默現象，可降低氨基酮戊酸（ALA）與卟膽原的積累，改善急性卟啉症發作症狀^[7]。美國食品藥品監督管理局已於2019年核准為治療急性肝性卟啉症（AHP）的成人用藥^[8]，並認為它是該領域的首創藥物^[9]。

註腳

[註 1]
repeat-induced point mutation
[註 2]
gene quelling^[4]
[註 3]
meiotic silencing by unpaired DNA，MSUD^[4]

參考文獻

[1]
Redberry, Grace. Gene silencing : new research. New York: Nova Science Publishers. 2006. ISBN 9781594548321.
[2]
Gene Silencing. National Center for Biotechnology Information. [11 November 2013]. （原始內容存檔於2017-11-08）.
[3]
Hood ME, Katawczik M, Giraud T. Repeat-induced point mutation and the population structure of transposable elements in Microbotryum violaceum.. Genetics. 2005, 170 (3): 1081–9. PMC 1451165 . PMID 15911572. doi:10.1534/genetics.105.042564.
[4]
Nakayashiki H. RNA silencing in fungi: mechanisms and applications.. FEBS Lett. 2005, 579 (26): 5950–7. PMID 16137680. doi:10.1016/j.febslet.2005.08.016.
[5]
Jing Q, Huang S, Guth S, Zarubin T, Motoyama A, Chen J; et al. Involvement of microRNA in AU-rich element-mediated mRNA instability.. Cell. 2005, 120 (5): 623–34. PMID 15766526. doi:10.1016/j.cell.2004.12.038.
[6]
Hood E. RNAi: What's all the noise about gene silencing?. Environmental Health Perspectives. March 2004, 112 (4): A224–9. PMC 1241909 . PMID 15033605. doi:10.1289/ehp.112-a224.
[7]
Scott LJ. Givosiran: First Approval. Drugs. 2020 Feb;80(3):335-339. doi: 10.1007/s40265-020-01269-0. PMID 32034693.
[8]
FDA approves givosiran for acute hepatic porphyria. U.S. Food and Drug Administration (FDA). [2021-10-21]. （原始內容存檔於2019-11-21）.
[9]
New Drug Therapy Approvals 2019. U.S. Food and Drug Administration. [2021-10-21]. （原始內容存檔於2020-09-16）.

[3] [註 1]
repeat-induced point mutation

[6] [註 2]
gene quelling^[4]

[7] [註 3]
meiotic silencing by unpaired DNA，MSUD^[4]

[redberry-1] [1]
Redberry, Grace. Gene silencing : new research. New York: Nova Science Publishers. 2006. ISBN 9781594548321.

[NCBI-2] [2]
Gene Silencing. National Center for Biotechnology Information. [11 November 2013]. （原始內容存檔於2017-11-08）.

[pmid15911572-4] [3]
Hood ME, Katawczik M, Giraud T. Repeat-induced point mutation and the population structure of transposable elements in Microbotryum violaceum.. Genetics. 2005, 170 (3): 1081–9. PMC 1451165 . PMID 15911572. doi:10.1534/genetics.105.042564.

[pmid16137680-5] [4]
Nakayashiki H. RNA silencing in fungi: mechanisms and applications.. FEBS Lett. 2005, 579 (26): 5950–7. PMID 16137680. doi:10.1016/j.febslet.2005.08.016.

[pmid15766526-8] [5]
Jing Q, Huang S, Guth S, Zarubin T, Motoyama A, Chen J; et al. Involvement of microRNA in AU-rich element-mediated mRNA instability.. Cell. 2005, 120 (5): 623–34. PMID 15766526. doi:10.1016/j.cell.2004.12.038.

[Hood-9] [6]
Hood E. RNAi: What's all the noise about gene silencing?. Environmental Health Perspectives. March 2004, 112 (4): A224–9. PMC 1241909 . PMID 15033605. doi:10.1289/ehp.112-a224.

[10] [7]
Scott LJ. Givosiran: First Approval. Drugs. 2020 Feb;80(3):335-339. doi: 10.1007/s40265-020-01269-0. PMID 32034693.

[11] [8]
FDA approves givosiran for acute hepatic porphyria. U.S. Food and Drug Administration (FDA). [2021-10-21]. （原始內容存檔於2019-11-21）.

[12] [9]
New Drug Therapy Approvals 2019. U.S. Food and Drug Administration. [2021-10-21]. （原始內容存檔於2020-09-16）.

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