Article
Biology
Jian-Ping Zhang, Zhi-Xue Yang, Feng Zhang, Ya-Wen Fu, Xin-Yue Dai, Wei Wen, Beldon Zhang, Hannah Choi, Wanqiu Chen, Meredith Brown, David Baylink, Lei Zhang, Hongyu Qiu, Charles Wang, Tao Cheng, Xiao-Bing Zhang
Summary: Research shows that HDAC inhibitors can increase the efficiency of genome editing, especially when dealing with silent genes. HDR efficiency improvement is more significant at closed loci.
SCIENCE CHINA-LIFE SCIENCES
(2021)
Article
Multidisciplinary Sciences
Zsolt Bodai, Alena L. Bishop, Valentino M. Gantz, Alexis C. Komor
Summary: Programmable double-strand DNA breaks (DSBs) can be harnessed for precision genome editing through manipulation of the homology-directed repair (HDR) pathway. This study introduces a general strategy called the double tap method, which improves HDR-mediated precision editing efficiency by taking advantage of the reproducible nature of indel sequences. The method utilizes multiple gRNAs, including a primary gRNA that targets the wild-type genomic sequence and one or more secondary gRNAs that target the most common indel sequence(s).
NATURE COMMUNICATIONS
(2022)
Review
Biochemistry & Molecular Biology
Ali Saber Sichani, Maryam Ranjbar, Maryam Baneshi, Farid Torabi Zadeh, Jafar Fallahi
Summary: In the field of medicine, the development of precise gene-editing tools, particularly CRISPR/Cas9, has revolutionized the potential for gene therapy in treating genetic diseases. This article discusses the different types of CRISPR/Cas-based gene-editing techniques, their functions, and the ongoing research studies that aim to improve their efficiency and reliability for future gene therapies. The article also compares the capabilities of these platforms and highlights their potential limitations.
MOLECULAR BIOTECHNOLOGY
(2023)
Article
Biotechnology & Applied Microbiology
Jiyeon Kweon, Jung-Ki Yoon, An-Hee Jang, Ha Rim Shin, Ji-Eun See, Gayoung Jang, Jong-Il Kim, Yongsub Kim
Summary: The engineered prime editors leverage various PAM-flexible Cas9 variants to broaden the range of target sites and achieve high editing activity, successfully generating multiple types of mutations in cells. Additionally, they successfully introduce mutations such as BRAF V600E that cannot be induced by conventional prime editors, expanding the applicability of CRISPR-based prime editing technologies in biological research.
Article
Immunology
Huan Qin, Wenliang Zhang, Shiyao Zhang, Yuan Feng, Weihui Xu, Jia Qi, Qian Zhang, Chunxiu Xu, Shanshan Liu, Jia Zhang, Yushuang Lei, Wanqin Liu, Shuyu Feng, Jingjing Wang, Xuefei Fu, Zifen Xu, Ping Li, Kai Yao
Summary: The researchers developed a genome-editing tool called PESpRY, which combines the versatility of prime editors with the unconstrained PAM requirement of the SpRY Cas9 variant. Using this tool, they were able to successfully correct gene mutations in a mouse model of retinitis pigmentosa, leading to substantial restoration of vision.
JOURNAL OF EXPERIMENTAL MEDICINE
(2023)
Article
Biology
Zhiquan Liu, Siyu Chen, Wanhua Xie, Hao Yu, Liangxue Lai, Zhanjun Li
Summary: Researchers have revisited and engineered a compact Cas9 orthologue derived from Neisseria cinerea (NcCas9) for efficient genome editing in mammal cells. NcCas9 can recognize a PAM sequence (N4GYAT) that existing Cas9s cannot, and by optimizing its architecture and spacer length, editing efficacy is improved. NcCas9-derived Base editors can efficiently generate base conversions, and six anti-CRISPR proteins were identified as off-switches for NcCas9. NcCas9 successfully generated efficient editing of mouse embryos by microinjection of NcCas9 mRNA and the corresponding sgRNA.
COMMUNICATIONS BIOLOGY
(2022)
Article
Biotechnology & Applied Microbiology
Hui Kwon Kim, Goosang Yu, Jinman Park, Seonwoo Min, Sungtae Lee, Sungroh Yoon, Hyongbum Henry Kim
Summary: This study identified factors affecting PE2 efficiency through high-throughput evaluation and developed three computational models to predict pegRNA efficiency, which can be applied to edits of various types and positions. Spearman's correlations between 0.47 and 0.81 were found when testing the accuracy of the predictions using independent test data sets.
NATURE BIOTECHNOLOGY
(2021)
Article
Biotechnology & Applied Microbiology
Shengyao Zhi, Yuxi Chen, Guanglan Wu, Jinkun Wen, Jinni Wu, Qianyi Liu, Yang Li, Rui Kang, Sihui Hu, Jiahui Wang, Puping Liang, Junjiu Huang
Summary: Prime editor (PE) is a new genome editing tool that has the potential to correct the majority of known human genetic disease-related mutations. In this study, split-PEs were constructed and delivered using dual adenoassociated viruses (AAVs), successfully mediating gene editing in human cells and adult mouse retina.
Review
Biotechnology & Applied Microbiology
Zhangrao Huang, Gang Liu
Summary: Prime editing is a precise genome manipulation technology that utilizes the CRISPR-Cas9 system's search and replace approach, without the need for exogenous donor DNA and DNA double-strand breaks (DSBs). It offers a wider editing scope compared to base editing. Prime editing has shown promise in breeding and genomic functional studies of animals and plants, disease treatment, and modification of microbial strains, as it has been successfully applied in various plant cells, animal cells, and Escherichia coli. This paper provides a brief overview of the basic strategies of prime editing, summarizes its research progress and prospects in multiple species, and outlines various optimization strategies to improve its efficiency and specificity.
FRONTIERS IN BIOENGINEERING AND BIOTECHNOLOGY
(2023)
Review
Biochemistry & Molecular Biology
Yan Li, Wenjing Li, Jun Li
Summary: CRISPR/Cas9 technology, a revolutionary gene editing tool, has made significant advances in plant science, including recent breakthroughs in precise genome editing and the development of various platforms. These technologies have been successfully applied to plants, providing technical support for plant science and sustainable agricultural development.
JOURNAL OF GENETICS AND GENOMICS
(2021)
Article
Biotechnology & Applied Microbiology
James W. Nelson, Peyton B. Randolph, Simon P. Shen, Kelcee A. Everette, Peter J. Chen, Andrew Anzalone, Meirui An, Gregory A. Newby, Jonathan C. Chen, Alvin Hsu, David R. Liu
Summary: Prime editing technology enhances editing efficiency by optimizing the structure of pegRNAs, preventing degradation of the 3' region from affecting system activity, without increasing the risk of off-target editing.
NATURE BIOTECHNOLOGY
(2022)
Article
Biochemical Research Methods
Jordan L. Doman, Alexander A. Sousa, Peyton B. Randolph, Peter J. Chen, David R. Liu
Summary: Prime editing (PE) is a precise gene editing technology that enables programmable installation of substitutions, insertions, and deletions in cells and animals without requiring double-strand DNA breaks. PE is less dependent on cellular replication and endogenous DNA repair and can minimize undesired outcomes. Advances such as engineered pegRNAs and enhanced PE systems have further improved its efficiency and capabilities. Compared to other procedures for editing human cells, PE offers greater precision, versatility, and can be completed within a relatively short time frame.
Article
Biochemical Research Methods
Lijun Hao, Xiangdong Pu, Jingyuan Song
Summary: Prime editing, a new gene editing technology based on CRISPR/Cas, allows for direct and precise editing of specified DNA sites without double strand breaks and donor DNA, offering a wider range of editing types and potential editing capabilities compared to traditional CRISPR/Cas9 and base editing. Successfully developed in mammalian cells and applied in plants, prime editing has the advantage of direct DNA editing without causing double strand breaks, providing a new approach for genetic improvement in plants.
Review
Plant Sciences
Rajesh Yarra, Lingaraj Sahoo
Summary: Base editing is a promising genome editing tool for generating single-nucleotide changes in the rice genome, which is essential for developing new rice varieties with desirable agronomic traits to sustain global food security. Base editing technology utilizes adenosine or cytidine base editors for precise editing at the target region, making it an efficient and reliable tool for rice crop improvement. This review discusses different adenine and cytosine base editors developed for precise genome editing of rice, addressing the current progress, advances, limitations, and future perspectives of base editing technology for rice crop improvement.
PLANT CELL REPORTS
(2021)
Article
Biochemistry & Molecular Biology
Yuan Zhuang, Jiangle Liu, Hao Wu, Qingguo Zhu, Yongchang Yan, Haowei Meng, Peng R. Chen, Chengqi Yi
Summary: The HOPE method utilizes paired pegRNAs encoding the same edits to achieve high editing efficiency in human embryonic kidney and colorectal carcinoma cells, showing improved product purity compared to the original PE3 system. This enhanced tool has the potential to broaden both fundamental research and therapeutic applications of prime editing.
NATURE CHEMICAL BIOLOGY
(2022)
Article
Chemistry, Multidisciplinary
Yinping Guo, Xin Mao, Liang Xiong, Anjie Xia, Jing You, Guifeng Lin, Chengyong Wu, Luyi Huang, Yiwei Wang, Shengyong Yang
Summary: SET domain bifurcated protein 1 (SETDB1) is a histone lysine methyltransferase that is overexpressed in many cancers. By identifying a hit compound (Cpd1), the researchers discovered the potent and selective small molecule SETDB1-TTD inhibitor (R,R)-59, which showed high affinity and competitive inhibition properties, making it a valuable tool compound for exploring the biological functions of SETDB1-TTD.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2021)
Article
Chemistry, Medicinal
Yun Zhang, Anjie Xia, Shiyu Zhang, Guifeng Lin, Jingming Liu, Pei Chen, Bo Mu, Yan Jiao, Wenwen Xu, Mingxin Chen, Linli Li
Summary: A new class of CLK1 inhibitors, with compound 9e being the most potent, was discovered in this study. Compound 9e efficiently induces autophagy, decreases phosphorylation levels of CLK1 downstream substrates, and affects their subcellular redistribution, showing promise as a lead compound for drug discovery targeting CLK1 kinase.
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2021)
Article
Multidisciplinary Sciences
Jingxin Qiao, Yue-Shan Li, Rui Zeng, Feng-Liang Liu, Rong-Hua Luo, Chong Huang, Yi-Fei Wang, Jie Zhang, Baoxue Quan, Chenjian Shen, Xin Mao, Xinlei Liu, Weining Sun, Wei Yang, Xincheng Ni, Kai Wang, Ling Xu, Zi-Lei Duan, Qing-Cui Zou, Hai-Lin Zhang, Wang Qu, Yang-Hao-Peng Long, Ming-Hua Li, Rui-Cheng Yang, Xiaolong Liu, Jing You, Yangli Zhou, Rui Yao, Wen-Pei Li, Jing-Ming Liu, Pei Chen, Yang Liu, Gui-Feng Lin, Xin Yang, Jun Zou, Linli Li, Yiguo Hu, Guang-Wen Lu, Wei-Min Li, Yu-Quan Wei, Yong-Tang Zheng, Jian Lei, Shengyong Yang
Summary: The study designed and synthesized 32 new M-pro inhibitors containing bicycloproline, which showed inhibitory effects on SARS-CoV-2. Compounds MI-09 and MI-30 exhibited excellent antiviral activity in cell-based assays and significantly reduced lung viral loads and lung lesions in a transgenic mouse model of SARS-CoV-2 infection. Both also displayed good pharmacokinetic properties and safety in rats.
Article
Chemistry, Medicinal
Pei Chen, Huachao Bin, Yan Jiao, Guifeng Lin, Yun Zhang, Anjie Xia, Zhilin Pan, Jingxin Qiao, Yinping Guo, Jingming Liu, Yangli Zhou, Linli Li
Summary: A series of 6,7-dihydro-5H-pyrrolo[3,4-d]-pyrimidine derivatives have been discovered as a new class of ATR inhibitors, with compound 5g exhibiting strong inhibition against ATR kinase and displaying good anti-tumor activity.
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
(2022)
Article
Chemistry, Medicinal
Yan Jiao, Jinshan Nan, Bo Mu, Yun Zhang, Nenghua Zhou, Shunhua Yang, Shanshan Zhang, Wanting Lin, Falu Wang, Anjie Xia, Zhixing Cao, Pei Chen, Zhiling Pan, Guifeng Lin, Shulei Pan, Huachao Bin, Linli Li, Shengyong Yang
Summary: By screening against NLRP3-dependent pyroptosis, a novel compound J114 was discovered, which displayed significant inhibitory activity against human cell pyroptosis and showed distinct differences from existing pyroptosis inhibitors. Further studies revealed that J114 inhibited inflammasome activation by disrupting the interaction between NLRP3 or AIM2 and the adaptor protein ASC.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Article
Chemistry, Medicinal
Huachao Bin, Pei Chen, Ming Wu, Falu Wang, Guifeng Lin, Shulei Pan, Jingming Liu, Bo Mu, Jinshan Nan, Qiao Huang, Linli Li, Shengyong Yang
Summary: This study reports the discovery of a potent and highly selective ATR inhibitor, SKLB-197, which demonstrated strong activity against ATR and weak or no activity against other protein kinases. SKLB-197 showed significant antitumor activity against ATM-deficient tumors both in vitro and in vivo, and it exhibited favorable pharmacokinetic properties. These findings suggest that SKLB-197 could be a promising lead compound for drug discovery targeting ATR.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Article
Biochemistry & Molecular Biology
Xin Yang, Xuehui Wang, Zheng Xu, Chao Wu, Yangli Zhou, Yifei Wang, Guifeng Lin, Kan Li, Ming Wu, Anjie Xia, Jingming Liu, Lin Cheng, Jun Zou, Wei Yan, Zhenhua Shao, Shengyong Yang
Summary: This study presents the crystallographic and cryo-electron microscopy structures of CB1 receptor bound to the allosteric modulator ZCZ011. The results show that ZCZ011 induces rearrangement of TM2, promoting receptor activation and increasing the population of active receptors. In contrast, the negative allosteric modulator ORG27569 inhibits TM2 rearrangement. These findings provide insights into CB1 allosteric regulation and have implications for the rational design of allosteric modulators.
NATURE CHEMICAL BIOLOGY
(2022)
Article
Microbiology
Bao-Xue Quan, Huiping Shuai, An-Jie Xia, Yuxin Hou, Rui Zeng, Xin-Lei Liu, Gui-Feng Lin, Jing-Xin Qiao, Wen-Pei Li, Fa-Lu Wang, Kai Wang, Ren-Jie Zhou, Terrence Tsz-Tai Yuen, Ming-Xin Chen, Chaemin Yoon, Ming Wu, Shi-Yu Zhang, Chong Huang, Yi-Fei Wang, Wei Yang, Chenyu Tian, Wei-Min Li, Yu-Quan Wei, Kwok-Yung Yuen, Jasper Fuk-Woo Chan, Jian Lei, Hin Chu, Shengyong Yang
Summary: This study reports a promising lead compound, Y180, for oral drug development against SARS-CoV-2. Y180, an inhibitor of the main protease (Mpro), demonstrated therapeutic efficacy against wild-type SARS-CoV-2 and its variants, including the Omicron variant, after oral administration. It improved survival in a humanized mouse model.
NATURE MICROBIOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Rui Tao, Yanhong Wang, Yaoge Jiao, Yun Hu, Li Li, Lurong Jiang, Lifang Zhou, Junyan Qu, Qiang Chen, Shaohua Yao
Summary: Prime editors with Cas9-nickase and reverse transcriptase enable targeted precise editing of small DNA pieces, expanding the editing scope and improving efficiency and accuracy.
NUCLEIC ACIDS RESEARCH
(2022)
Article
Chemistry, Medicinal
Xin Yang, Guifeng Lin, Anjie Xia, Jingming Liu, Shiyu Zhang, Pei Zhou, Yiwei Wang, Jiahao Zhang, Yangli Zhou, Pei Chen, Yifei Wang, Tao Zheng, Linli Li, Shengyong Yang
Summary: GnRH is a central regulator of the human reproductive system and binds to GnRH1R to exert its effects. The development of GnRH1R agonists has potential therapeutic applications. This study successfully identified CD304 as a hit compound and optimized its structure to obtain compound 6d, which showed activation activity of GnRH1R.
JOURNAL OF CHEMICAL INFORMATION AND MODELING
(2022)
Correction
Medicine, Research & Experimental
Nan Liu, Lifang Zhou, Guifeng Lin, Yun Hu, Yaoge Jiao, Yanhong Wang, Jingming Liu, Shengyong Yang, Shaohua Yao
MOLECULAR THERAPY-NUCLEIC ACIDS
(2022)
Article
Chemistry, Medicinal
Jinshan Nan, Jingming Liu, Guifeng Lin, Shanshan Zhang, Anjie Xia, Pei Zhou, Yangli Zhou, Jiahao Zhang, Jinlong Zhao, Shiyu Zhang, Chong Huang, Yifei Wang, Qian Hu, Junxian Chen, Mingli Xiang, Xin Yang, Shengyong Yang
Summary: A new class of CB2 agonists, 4-(1,2,4-oxadiazol-5-yl)azepan-2-one derivatives, has been discovered. Compound 25r showed high selectivity for CB2 receptor and exhibited significant efficacy in relieving rodent inflammatory pain, suggesting its potential as a lead compound for treating inflammatory pain.
JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Article
Ophthalmology
Yun Zhang, Nenghua Zhou, Yan Jiao, Guifeng Lin, Xun Li, Sheng Gao, Pei Zhou, Jingming Liu, Jinshan Nan, Meixia Zhang, Shengyong Yang
Summary: In this study, we discovered that J114 efficiently inhibits LPS-induced noncanonical pyroptosis and revealed the underlying mechanism. This compound exhibited significant anti-inflammatory activity in the LPS-induced keratitis mouse model. These findings suggest that J114 could be a potential lead compound for drug development against inflammatory ocular surface diseases.
INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE
(2023)
