Avoiding the off-target effects of CRISPR/cas9 system is still a challenging accomplishment for genetic transformation

被引:20
作者
Herai, Roberto H. [1 ,2 ]
机构
[1] Pontificia Univ Catolica Parana PUCPR, Grad Program Hlth Sci, Sch Med, BR-80215901 Curitiba, Parana, Brazil
[2] Inst Lico Kaesemodel, Div Res, Curitiba, Parana, Brazil
关键词
CRISPR/cas9; system; Off-target effects; Genetic transformation; GENOME; SPECIFICITY; CLEAVAGE; DESIGN;
D O I
10.1016/j.gene.2019.03.019
中图分类号
Q3 [遗传学];
学科分类号
071007 ; 090102 ;
摘要
The recent disclosure of a human embryo subjected to a genetic transformation using the CRISPR/cas9 system give rise to several concerns on ethical questions about its uncontrolled use in humans. Although CRISPR/cas9 has demonstrated its efficiency, this system still lacks the capability to avoid the introduction of undesirable mutations through the target genome. In this Letter, we present several undesirable impacts that CRISPR/cas9 system have in the genetic transformation of the human genome. We briefly discuss, using the very recent literature from distinct high impact journals, the main concerns related to CRISPR/cas9 to deal with off-target effects and how the research community has treated it.
引用
收藏
页码:176 / 178
页数:3
相关论文
共 42 条
[21]   No unexpected CRISPR-Cas9 off-target activity revealed by trio sequencing of gene-edited mice [J].
Iyer, Vivek ;
Boroviak, Katharina ;
Thomas, Mark ;
Doe, Brendan ;
Riva, Laura ;
Ryder, Edward ;
Adams, David J. .
PLOS GENETICS, 2018, 14 (07)
[22]   Strategies for controlling CRISPR/Cas9 off-target effects and biological variations in mammalian genome editing experiments [J].
Kimberland, Michelle L. ;
Hou, Wangfang ;
Alfonso-Pecchio, Adolfo ;
Wilson, Stephen ;
Rao, Yanhua ;
Zhang, Shu ;
Lu, Quinn .
JOURNAL OF BIOTECHNOLOGY, 2018, 284 :91-101
[23]   Hybridization Kinetics Explains CRISPR-Cas Off-Targeting Rules [J].
Klein, Misha ;
Eslami-Mossallam, Behrouz ;
Arroyo, Dylan Gonzalez ;
Depken, Martin .
CELL REPORTS, 2018, 22 (06) :1413-1423
[24]   Loss-of-function variants of SETD5 cause intellectual disability and the core phenotype of microdeletion 3p25.3 syndrome [J].
Kuechler, Alma ;
Zink, Alexander M. ;
Wieland, Thomas ;
Luedecke, Hermann-Josef ;
Cremer, Kirsten ;
Salviati, Leonardo ;
Magini, Pamela ;
Najafi, Kimia ;
Zweier, Christiane ;
Czeschik, Johanna Christina ;
Aretz, Stefan ;
Endele, Sabine ;
Tamburrino, Federica ;
Pinato, Claudia ;
Clementi, Maurizio ;
Gundlach, Jasmin ;
Maylahn, Carina ;
Mazzanti, Laura ;
Wohlleber, Eva ;
Schwarzmayr, Thomas ;
Kariminejad, Roxana ;
Schlessinger, Avner ;
Wieczorek, Dagmar ;
Strom, Tim M. ;
Novarino, Gaia ;
Engels, Hartmut .
EUROPEAN JOURNAL OF HUMAN GENETICS, 2015, 23 (06) :753-760
[25]   Off-target predictions in CRISPR-Cas9 gene editing using deep learning [J].
Lin, Jiecong ;
Wong, Ka-Chun .
BIOINFORMATICS, 2018, 34 (17) :656-663
[26]   Prediction of off-target activities for the end-to-end design of CRISPR guide RNAs [J].
Listgarten, Jennifer ;
Weinstein, Michael ;
Kleinstiver, Benjamin P. ;
Sousa, Alexander A. ;
Joung, J. Keith ;
Crawford, Jake ;
Gao, Kevin ;
Hoang, Luong ;
Elibol, Melih ;
Doench, John G. ;
Fusi, Nicolo .
NATURE BIOMEDICAL ENGINEERING, 2018, 2 (01) :38-47
[27]   Multiple homologous genes knockout (KO) by CRISPR/Cas9 system in rabbit [J].
Liu, Huan ;
Sui, Tingting ;
Liu, Di ;
Liu, Tingjun ;
Chen, Mao ;
Deng, Jichao ;
Xu, Yuanyuan ;
Li, Zhanjun .
GENE, 2018, 647 :261-267
[28]   Sequence features associated with the cleavage efficiency of CRISPR/Cas9 system [J].
Liu, Xiaoxi ;
Homma, Ayaka ;
Sayadi, Jamasb ;
Yang, Shu ;
Ohashi, Jun ;
Takumi, Toru .
SCIENTIFIC REPORTS, 2016, 6
[29]   Genome-editing Technologies for Gene and Cell Therapy [J].
Maeder, Morgan L. ;
Gersbach, Charles A. .
MOLECULAR THERAPY, 2016, 24 (03) :430-446
[30]   TALEN and CRISPR/Cas Genome Editing Systems: Tools of Discovery [J].
Nemudryi, A. A. ;
Valetdinova, K. R. ;
Medvedev, S. P. ;
Zakian, S. M. .
ACTA NATURAE, 2014, 6 (03) :19-40