Highly efficient RNA-guided base editing in mouse embryos

2017 ◽  
Vol 35 (5) ◽  
pp. 435-437 ◽  
Author(s):  
Kyoungmi Kim ◽  
Seuk-Min Ryu ◽  
Sang-Tae Kim ◽  
Gayoung Baek ◽  
Daesik Kim ◽  
...  
Keyword(s):  
Mouse Embryos ◽  
Base Editing ◽  
Highly Efficient

scholarly journals Highly efficient targeted mutagenesis in one-cell mouse embryos mediated by the TALEN and CRISPR/Cas systems

2014 ◽  
Vol 4 (1) ◽  
Author(s):  
Akihiro Yasue ◽  
Silvia Naomi Mitsui ◽  
Takahito Watanabe ◽  
Tetsushi Sakuma ◽  
Seiichi Oyadomari ◽  
...  
Keyword(s):  
Mouse Embryos ◽  
Targeted Mutagenesis ◽  
Highly Efficient

scholarly journals Highly efficient base editing in human tripronuclear zygotes

2017 ◽  
Vol 8 (10) ◽  
pp. 772-775 ◽  
Author(s):  
Changyang Zhou ◽  
Meiling Zhang ◽  
Yu Wei ◽  
Yidi Sun ◽  
Yun Sun ◽  
...  
Keyword(s):  
Base Editing ◽  
Highly Efficient

scholarly journals Cytosine base editor 4 but not adenine base editor generates off-target mutations in mouse embryos

2020 ◽  
Vol 3 (1) ◽  
Author(s):  
Hye Kyung Lee ◽  
Harold E. Smith ◽  
Chengyu Liu ◽  
Michaela Willi ◽  
Lothar Hennighausen
Keyword(s):  
Point Mutations ◽  
Mouse Embryos ◽  
Single Nucleotide Variants ◽  
Single Nucleotide ◽  
Base Editing ◽  
Genome Wide ◽  
Wide Range ◽  
Family Based ◽  
Correct Point ◽  
Adenine Base

AbstractDeaminase base editing has emerged as a tool to install or correct point mutations in the genomes of living cells in a wide range of organisms. However, the genome-wide off-target effects introduced by base editors in the mammalian genome have been examined in only one study. Here, we have investigated the fidelity of cytosine base editor 4 (BE4) and adenine base editors (ABE) in mouse embryos using unbiased whole-genome sequencing of a family-based trio cohort. The same sgRNA was used for BE4 and ABE. We demonstrate that BE4-edited mice carry an excess of single-nucleotide variants and deletions compared to ABE-edited mice and controls. Therefore, an optimization of cytosine base editors is required to improve its fidelity. While the remarkable fidelity of ABE has implications for a wide range of applications, the occurrence of rare aberrant C-to-T conversions at specific target sites needs to be addressed.

scholarly journals 337. CRISPR/Cas9 Mediated Highly Efficient Genome Engineering in Mouse Embryos

2015 ◽  
Vol 23 ◽  
pp. S135
Author(s):  
Khurshida Begum ◽  
Bert W. O'Malley ◽  
Francesco J. DeMayo ◽  
Paul Overbeek
Keyword(s):  
Genome Engineering ◽  
Mouse Embryos ◽  
Highly Efficient

scholarly journals Prime editing primarily induces undesired outcomes in mice

2020 ◽  
Author(s):  
Tomomi Aida ◽  
Jonathan J. Wilde ◽  
Lixin Yang ◽  
Yuanyuan Hou ◽  
Mengqi Li ◽  
...  
Keyword(s):  
Genome Editing ◽  
High Frequency ◽  
Mouse Embryos ◽  
Biomedical Science ◽  
New Approach ◽  
Chemically Modified ◽  
Highly Efficient ◽  
Large Deletions

SummaryGenome editing has transformed biomedical science, but is still unpredictable and often induces undesired outcomes. Prime editing (PE) is a promising new approach due to its proposed flexibility and ability to avoid unwanted indels. Here, we show highly efficient PE-mediated genome editing in mammalian zygotes. Utilizing chemically modified guideRNAs, PE efficiently introduced 10 targeted modifications including substitutions, deletions, and insertions across 6 genes in mouse embryos. However, we unexpectedly observed a high frequency of undesired outcomes such as large deletions and found that these occurred more often than pure intended edits across all of the edits/genes. We show that undesired outcomes result from the double-nicking PE3 strategy, but that omission of the second nick largely ablates PE function. However, sequential double-nicking with PE3b, which is only applicable to a fraction of edits, eliminated undesired outcomes. Overall, our findings demonstrate the promising potential of PE for predictable, flexible, and highly efficient in vivo genome editing, but highlight the need for improved variations of PE before it is ready for widespread use.

scholarly journals Cytosine but not adenine base editor generates mutations in mice

2019 ◽  
Author(s):  
Hye Kyung Lee ◽  
Harold E. Smith ◽  
Chengyu Liu ◽  
Michaela Willi ◽  
Lothar Hennighausen
Keyword(s):  
Point Mutations ◽  
Living Cells ◽  
Mouse Embryos ◽  
Single Nucleotide Variants ◽  
Single Nucleotide ◽  
Base Editing ◽  
Wide Range ◽  
Family Based ◽  
Correct Point ◽  
Adenine Base

ABSTRACTDeaminase base editing has emerged as a tool to install or correct point mutations in the genomes of living cells in a wide range of organisms and its ultimate success therapeutically depends on its accuracy. Here we have investigated the fidelity of cytosine base editor 4 (BE4) and adenine base editor (ABE) in mouse embryos using unbiased whole genome sequencing of a family-based trio cohort. We demonstrate that BE4-edited mice carry an excess of single-nucleotide variants and deletions compared to ABE-edited mice and controls.

scholarly journals Highly efficient single base editing in Aspergillus niger with CRISPR/Cas9 cytidine deaminase fusion

2019 ◽  
Vol 223-225 ◽  
pp. 44-50 ◽  
Author(s):  
Lianggang Huang ◽  
Hongzhi Dong ◽  
Junwei Zheng ◽  
Bin Wang ◽  
Li Pan
Keyword(s):  
Aspergillus Niger ◽  
Cytidine Deaminase ◽  
Single Base ◽  
Base Editing ◽  
Highly Efficient

scholarly journals Highly efficient generation of sheep with a defined FecBB mutation via adenine base editing

2020 ◽  
Vol 52 (1) ◽  
Author(s):  
Shiwei Zhou ◽  
Yige Ding ◽  
Jiao Liu ◽  
Yao Liu ◽  
Xiaoe Zhao ◽  
...  
Keyword(s):  
Base Editing ◽  
Highly Efficient ◽  
Efficient Generation ◽  
Adenine Base
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