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Base editing in pigs for precision breeding

Ruigao SONG, Yu WANG, Yanfang WANG, Jianguo ZHAO

《农业科学与工程前沿(英文)》 2020年 第7卷 第2期   页码 161-170 doi: 10.15302/J-FASE-2019308

摘要:

Pigs are one of the most important domesticated animals and have great value in agriculture and biomedicine. Single nucleotide polymorphisms (SNPs) are a dominant type of genetic variation among individual pigs and contribute to the formation of traits. Precision single base substitution provides a strategy for accurate genetic improvement in pig production with the characterization of functional SNPs and genetic variants in pigs. Base editing has recently been developed as the latest gene-editing tool that can directly make changes in single nucleotides without introducing double-stranded DNA breaks (DSBs), providing a promising solution for precise genetic modification in large animals. This review summarizes gene-editing developments and highlights recent genetic dissection related to SNPs in major economic traits which may have the potential to be modified using SNP-editing applications. In addition, limitations and future directions of base editing in pig breeding are discussed.

关键词: base editing     genetic improvement     pigs     single nucleotide polymorphisms    

Base editing technology

Yidi SUN, Erwei ZUO, Hui YANG

《农业科学与工程前沿(英文)》 2020年 第7卷 第2期   页码 227-228 doi: 10.15302/J-FASE-2020321

Base editors: development and applications in biomedicine

《医学前沿(英文)》 2023年 第17卷 第3期   页码 359-387 doi: 10.1007/s11684-023-1013-y

摘要: Base editor (BE) is a gene-editing tool developed by combining the CRISPR/Cas system with an individual deaminase, enabling precise single-base substitution in DNA or RNA without generating a DNA double-strand break (DSB) or requiring donor DNA templates in living cells. Base editors offer more precise and secure genome-editing effects than other conventional artificial nuclease systems, such as CRISPR/Cas9, as the DSB induced by Cas9 will cause severe damage to the genome. Thus, base editors have important applications in the field of biomedicine, including gene function investigation, directed protein evolution, genetic lineage tracing, disease modeling, and gene therapy. Since the development of the two main base editors, cytosine base editors (CBEs) and adenine base editors (ABEs), scientists have developed more than 100 optimized base editors with improved editing efficiency, precision, specificity, targeting scope, and capacity to be delivered in vivo, greatly enhancing their application potential in biomedicine. Here, we review the recent development of base editors, summarize their applications in the biomedical field, and discuss future perspectives and challenges for therapeutic applications.

关键词: base editing     CBE     ABE     ADAR     DdCBE     disease model     therapeutic application    

用于分枝杆菌碱基编辑的PAM扩展型嗜热链球菌Cas9 C到T和C到G碱基编辑器 Article

张洪源, 张翼飞, 王卫晓, 陈未中, 张侠, 黄行许, 陈伟, 季泉江

《工程(英文)》 2022年 第15卷 第8期   页码 67-77 doi: 10.1016/j.eng.2022.02.013

摘要:

结核分枝杆菌(Mycobacterium tuberculosis, MTB)耐药性是临床治疗面临的重大挑战,迫切需要开发治疗耐药结核病的新型策略,而简单易用的MTB遗传操作方法能够加速这一进程。依赖于规律成簇的间隔短回文重复序列(CRISPR)的碱基编辑器能够快速有效地进行碱基编辑和基因失活,然而,目前还没有开发出可用于MTB的碱基编辑器。通过筛选不同的碱基编辑器,发现广泛使用的酿脓链球菌CRISPR相关蛋白9(SpCas9)或毛螺科菌Cpf1(LbCpf1)胞嘧啶碱基编辑器在分枝杆菌中不具有活性,而嗜热链球菌Cas9(St1Cas9)胞嘧啶碱基编辑器活性较好。虽然使用St1Cas9 胞嘧啶碱基编辑器能够实现C到T的碱基编辑,但是,在碱基编辑过程中却产生了大量的副产物。将尿嘧啶-N-糖基化酶抑制剂或尿嘧啶-N-糖基化酶分别融合到St1Cas9 胞嘧啶碱基编辑器中,得到了两种新的碱基编辑器——CTBE和CGBE,能将C分别转化为T或G。将CTBE和CGBE用于耻垢分枝杆菌的基因编辑时,产物的纯度得到了提高,并且能够进行多位点编辑。此外,由于野生型St1Cas9 在靶向DNA序列时需要识别严格的前间隔序列邻近基序(PAM),因此,通过结构介导的蛋白质工程设计了PAM扩展的St1Cas9,扩大了碱基编辑器的靶向范围。首先在耻垢分枝杆菌中测试了CTBE和CGBE的编辑效率,随后测试了CTBE在MTB中的编辑效率。本文提出的方法显著减少了在MTB中进行精确遗传操作所需要的时间,并将推动分枝杆菌功能基因组学、抗生素-耐药性机制研究和药物-靶点研究的发展。

关键词: CRISPR     Cas9     结核分枝杆菌     基因编辑     碱基编辑    

Genome-edited crops: how to move them from laboratory to market

Kunling CHEN, Caixia GAO

《农业科学与工程前沿(英文)》 2020年 第7卷 第2期   页码 181-187 doi: 10.15302/J-FASE-2020332

摘要:

Recent breakthroughs in CRISPR technology allow specific genome manipulation of almost all crops and have initiated a revolution in precision crop breeding. Rationally-based regulation and widespread public acceptance are needed to propel genome-edited crops from laboratory to market and to translate this innovative technology into agricultural productivity.

关键词: CRISPR/Cas     genome editing     base editing     precision breeding     regulation    

Highlights of special issue “Genome Editing in Agriculture: Technology, Applications and Regulations”

Yaofeng ZHAO, Caixia GAO, Sen WU

《农业科学与工程前沿(英文)》 2020年 第7卷 第2期   页码 121-122 doi: 10.15302/J-FASE-2019317

Search-and-replace editing of genetic information

Yao LIU, Xingxu HUANG, Xiaolong WANG

《农业科学与工程前沿(英文)》 2020年 第7卷 第2期   页码 231-232 doi: 10.15302/J-FASE-2020322

Embryo-mediated genome editing for accelerated genetic improvement of livestock

Zachariah MCLEAN, Björn OBACK, Götz LAIBLE

《农业科学与工程前沿(英文)》 2020年 第7卷 第2期   页码 148-160 doi: 10.15302/J-FASE-2019305

摘要:

Selecting beneficial DNA variants is the main goal of animal breeding. However, this process is inherently inefficient because each animal only carries a fraction of all desirable variants. Genome editing technology with its ability to directly introduce beneficial sequence variants offers new opportunities to modernize animal breeding by overcoming this biological limitation and accelerating genetic gains. To realize rapid genetic gain, precise edits need to be introduced into genomically-selected embryos, which minimizes the genetic lag. However, embryo-mediated precision editing by homology-directed repair (HDR) mechanisms is currently an inefficient process that often produces mosaic embryos and greatly limits the numbers of available edited embryos. This review provides a summary of genome editing in bovine embryos and proposes an embryo-mediated accelerated breeding scheme that overcomes the present efficiency limitations of HDR editing in bovine embryos. It integrates embryo-based genomic selection with precise multi-editing and uses embryonic cloning with elite edited blastomeres or embryonic pluripotent stem cells to resolve mosaicism, enable multiplex editing and multiply rare elite genotypes. Such a breeding strategy would enable a more targeted, accelerated approach for livestock improvement that allows stacking of beneficial variants, even including novel traits from outside the breeding population, in the most recent elite genetic background, essentially within a single generation.

关键词: animal breeding     cattle     cloning     CRISPR/Cas9     cytoplasmic injection     embryo     genome editing     germline chimaeras     HDR     livestock improvement     TALENs    

A brief review of genome editing technology for generating animal models

Haoyi WANG, Sen WU, Mario R. CAPECCHI, Rudolf JAENISCH

《农业科学与工程前沿(英文)》 2020年 第7卷 第2期   页码 123-128 doi: 10.15302/J-FASE-2019309

摘要:

The recent development of genome editing technologies has given researchers unprecedented power to alter DNA sequences at chosen genomic loci, thereby generating various genetically edited animal models. This mini-review briefly summarizes the development of major genome editing tools, focusing on the application of these tools to generate animal models in multiple species.

关键词: animal model     CRISPR     genome editing     TALEN     ZFN    

The development and application of genome editing technology in ruminants: a review

Mengke YUAN, Yuanpeng GAO, Jing HAN, Teng WU, Jingcheng ZHANG, Yongke WEI, Yong ZHANG

《农业科学与工程前沿(英文)》 2020年 第7卷 第2期   页码 171-180 doi: 10.15302/J-FASE-2019302

摘要:

Transgenic ruminants are a valuable resource for both animal breeding and biomedical research. The development of transgenic breeding is proceeding slowly, because it suffers from low efficiency of gene transfer and possible safety problems from uncontrolled random integration. However, new breeding methods combined with genome editing and somatic cell nuclear transfer or microinjection can offer an economic and efficient way to produce gene-edited ruminants, which can serve as bioreactors or have improved disease resistance, animal welfare and product quality. Recent advances in precise genome editing technologies, especially clustered regularly interspaced short palindromic repeat (CRISPR)/Cas9 nucleases, are enabling the systematic development of gene-edited ruminant production. This review covers the development of gene-edited ruminants, the particulars of site-specific engineered nucleases and the state of the art and new insights into practical applications and social acceptance of genome editing technology in ruminants. It is concluded that the production of gene-edited ruminants is feasible and through improvements in genome editing technology it is possible to help feed the world.

关键词: bioreactors     breeding     engineered endonucleases     genome editing     ruminants    

Gene-editing in plants no longer requires tissue culture

Yi ZHANG, Michael PALMGREN

《农业科学与工程前沿(英文)》 2020年 第7卷 第2期   页码 229-230 doi: 10.15302/J-FASE-2020330

GENOME EDITING: A GROUND BREAKING RESEARCH HAS BEEN RANKED TOP 10 ENGINEERING FRONTS FROM 2017 TO 2021

《农业科学与工程前沿(英文)》 2022年 第9卷 第2期   页码 309-311 doi: 10.15302/J-FASE-2022440

Study of base friction simulation tests based on a complicated engineered bridge slope

Liu HE, Guang WU, Hua WANG

《结构与土木工程前沿(英文)》 2012年 第6卷 第4期   页码 393-397 doi: 10.1007/s11709-012-0174-6

摘要: In this paper, a physical base friction test model of a slope is established. The model is based on similarity principles and the geological conditions of a complicated bridge slope during construction, deformation and failure. The behavior of the slope in both its natural state and during excavation loading is qualitatively analyzed through base friction tests. The base friction test results are then subjected to comparison and analysis using finite element numerical simulation. The findings show that the whole engineered slope tends to stabilize in its natural state, whereas instabilities will arise at faulted rock masses located near bridge piers during excavation loading. Therefore, to ensure normal construction operation of bridge works, it is suggested that pre-reinforcement of faulted rock masses be performed.

关键词: base friction test     slope stability evaluation     bridge slope    

Livestock breeding for the 21st century: the promise of the editing revolution

Chris PROUDFOOT, Gus MCFARLANE, Bruce WHITELAW, Simon LILLICO

《农业科学与工程前沿(英文)》 2020年 第7卷 第2期   页码 129-135 doi: 10.15302/J-FASE-2019304

摘要:

In recent years there has been a veritable explosion in the use of genome editors to create site-specific changes, both and , to the genomes of a multitude of species for both basic research and biotechnology. Livestock, which form a vital component of most societies, are no exception. While selective breeding has been hugely successful at enhancing some production traits, the rate of progress is often slow and is limited to variants that exist within the breeding population. Genome editing provides the potential to move traits between breeds, in a single generation, with no impact on existing productivity or to develop phenotypes that tackle intractable issues such as disease. As such, genome editors provide huge potential for ongoing livestock development programs in light of increased demand and disease challenge. This review will highlight some of the more notable agricultural applications of this technology in livestock.

关键词: cattle     pig     sheep     chicken     aquaculture     CRISPR    

Genome editing for the treatment of tumorigenic viral infections and virus-related carcinomas

Lan Yu, Xun Tian, Chun Gao, Ping Wu, Liming Wang, Bei Feng, Xiaomin Li, Hui Wang, Ding Ma, Zheng Hu

《医学前沿(英文)》 2018年 第12卷 第5期   页码 497-508 doi: 10.1007/s11684-017-0572-1

摘要:

Viral infections cause at least 10%–15% of all human carcinomas. Over the last century, the elucidation of viral oncogenic roles in many cancer types has provided fundamental knowledge on carcinogenetic mechanisms and established a basis for the early intervention of virus-related cancers. Meanwhile, rapidly evolving genome-editing techniques targeting viral DNA/RNA have emerged as novel therapeutic strategies for treating virus-related carcinogenesis and have begun showing promising results. This review discusses the recent advances of genome-editing tools for treating tumorigenic viruses and their corresponding cancers, the challenges that must be overcome before clinically applying such genome-editing technologies, and more importantly, the potential solutions to these challenges.

关键词: genome-editing tools     tumorigenic virus     delivery method     off-target effect     virus-related carcinoma    

标题 作者 时间 类型 操作

Base editing in pigs for precision breeding

Ruigao SONG, Yu WANG, Yanfang WANG, Jianguo ZHAO

期刊论文

Base editing technology

Yidi SUN, Erwei ZUO, Hui YANG

期刊论文

Base editors: development and applications in biomedicine

期刊论文

用于分枝杆菌碱基编辑的PAM扩展型嗜热链球菌Cas9 C到T和C到G碱基编辑器

张洪源, 张翼飞, 王卫晓, 陈未中, 张侠, 黄行许, 陈伟, 季泉江

期刊论文

Genome-edited crops: how to move them from laboratory to market

Kunling CHEN, Caixia GAO

期刊论文

Highlights of special issue “Genome Editing in Agriculture: Technology, Applications and Regulations”

Yaofeng ZHAO, Caixia GAO, Sen WU

期刊论文

Search-and-replace editing of genetic information

Yao LIU, Xingxu HUANG, Xiaolong WANG

期刊论文

Embryo-mediated genome editing for accelerated genetic improvement of livestock

Zachariah MCLEAN, Björn OBACK, Götz LAIBLE

期刊论文

A brief review of genome editing technology for generating animal models

Haoyi WANG, Sen WU, Mario R. CAPECCHI, Rudolf JAENISCH

期刊论文

The development and application of genome editing technology in ruminants: a review

Mengke YUAN, Yuanpeng GAO, Jing HAN, Teng WU, Jingcheng ZHANG, Yongke WEI, Yong ZHANG

期刊论文

Gene-editing in plants no longer requires tissue culture

Yi ZHANG, Michael PALMGREN

期刊论文

GENOME EDITING: A GROUND BREAKING RESEARCH HAS BEEN RANKED TOP 10 ENGINEERING FRONTS FROM 2017 TO 2021

期刊论文

Study of base friction simulation tests based on a complicated engineered bridge slope

Liu HE, Guang WU, Hua WANG

期刊论文

Livestock breeding for the 21st century: the promise of the editing revolution

Chris PROUDFOOT, Gus MCFARLANE, Bruce WHITELAW, Simon LILLICO

期刊论文

Genome editing for the treatment of tumorigenic viral infections and virus-related carcinomas

Lan Yu, Xun Tian, Chun Gao, Ping Wu, Liming Wang, Bei Feng, Xiaomin Li, Hui Wang, Ding Ma, Zheng Hu

期刊论文