Cytosine and adenine deaminase base-editors induce broad and nonspecific changes in gene expression and splicing.
Cytosine and adenine deaminase base-editors induce broad and nonspecific changes in gene expression and splicing.
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胞嘧啶和腺嘌呤脱氨酶碱基编辑器诱导基因表达和剪接的广泛和非特异性变化
DOI：
10.1038/s42003-021-02406-5
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发表时间：
2021-07-16
影响因子：
5.9
通讯作者：
Shu W
中科院分区：
文献类型：
--
作者：
Fan J;Ding Y;Ren C;Song Z;Yuan J;Chen Q;Du C;Li C;Wang X;Shu W
Cytosine or adenine base editors (CBEs or ABEs) hold great promise in therapeutic applications because they enable the precise conversion of targeted base changes without generating of double-strand breaks. However, both CBEs and ABEs induce substantial off-target DNA editing, and extensive off-target RNA single nucleotide variations in transfected cells. Therefore, the potential effects of deaminases induced by DNA base editors are of great importance for their clinical applicability. Here, the transcriptome-wide deaminase effects on gene expression and splicing is examined. Differentially expressed genes (DEGs) and differential alternative splicing (DAS) events, induced by base editors, are identified. Both CBEs and ABEs generated thousands of DEGs and hundreds of DAS events. For engineered CBEs or ABEs, base editor-induced variants had little effect on the elimination of DEGs and DAS events. Interestingly, more DEGs and DAS events are observed as a result of over expressions of cytosine and adenine deaminases. This study reveals a previously overlooked aspect of deaminase effects in transcriptome-wide gene expression and splicing, and underscores the need to fully characterize such effects of deaminase enzymes in base editor platforms.
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DOI：
10.1093/bioinformatics/btu638
发表时间：
2015-01-15
期刊：
Bioinformatics (Oxford, England)
影响因子：
--
作者：
Anders S;Pyl PT;Huber W
通讯作者：
Huber W
影响因子：
64.8
作者：
Komor AC;Kim YB;Packer MS;Zuris JA;Liu DR
通讯作者：
Liu DR
影响因子：
11.2
作者：
Monge, Marta;Colas, Eva;Abal, Miguel
通讯作者：
Abal, Miguel
影响因子：
82.9
作者：
Maeder, Morgan L.;Stefanidakis, Michael;Jiang, Haiyan
通讯作者：
Jiang, Haiyan
DOI：
10.1126/science.abb1390
发表时间：
2020-07-31
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Lapinaite A;Knott GJ;Palumbo CM;Lin-Shiao E;Richter MF;Zhao KT;Beal PA;Liu DR;Doudna JA
通讯作者：
Doudna JA