Article
Biochemistry & Molecular Biology
Zhongsen Li, Rui Ma, Dan Liu, Mingyue Wang, Ting Zhu, Yanxue Deng
Summary: CRISPR Cas9-mediated genome editing and base editing technologies have shown promising results in plant gene editing, with prime editing demonstrating high efficiency and precision. However, addressing the issue of inconsistent editing efficiencies across different target sites remains a challenge.
Article
Biology
Hanqin Li, Oriol Busquets, Yogendra Verma, Khaja Mohieddin Syed, Nitzan Kutnowski, Gabriella R. Pangilinan, Luke A. Gilbert, Helen S. Bateup, Donald C. Rio, Dirk Hockemeyer, Frank Soldner
Summary: Recent development of prime editing technology has the potential to simplify the generation of human pluripotent stem cell-based disease models. It is more efficient and precise than conventional gene editing methods, particularly in generating disease-associated mutations. By optimizing the delivery modalities, editing efficiency can be further improved.
Article
Biochemistry & Molecular Biology
Pierre-Francois Perroud, Anouchka Guyon-Debast, Florian Veillet, Marie-Paule Kermarrec, Laura Chauvin, Jean-Eric Chauvin, Jean-Luc Gallois, Fabien Nogue
Summary: The introduction of CRISPR-Cas9 technology has revolutionized plant research and precision crop breeding, while the development of Prime Editing technology has opened up new possibilities for precise genome editing in plants. Successful application of Prime Editing in Physcomitrium patens and potato demonstrated its unique advantage in introducing nucleotide substitutions, with high targeting fidelity observed in P. patens.
Article
Biochemistry & Molecular Biology
Sudip Biswas, Aya Bridgeland, Samra Irum, Michael J. Thomson, Endang M. Septiningsih
Summary: Prime editing is a newly developed precise editing technology that can be widely applied to plant genome editing, including different crops. In rice, peanut, chickpea, and cowpea, the use of dual pegRNA vectors can significantly increase the efficiency of Prime editing. These initial results are of great significance for accelerating legume breeding programs to accelerate crop improvement.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Medicine, Research & Experimental
Ding Zhao, Yuqiang Qian, Jinze Li, Zhanjun Li, Liangxue Lai
Summary: This study shows that ABE8.17 systems can efficiently induce base editing in mouse and rabbit embryos, as well as accurately mimic clinical point mutations in rabbits. ABE8.17-NL, created by eliminating the linker, achieved efficient base editing within a narrowed window in human cells.
MOLECULAR THERAPY-NUCLEIC ACIDS
(2022)
Article
Biochemistry & Molecular Biology
Peter J. Chen, Jeffrey A. Hussmann, Jun Yan, Friederike Knipping, Purnima Ravisankar, Pin-Fang Chen, Cidi Chen, James W. Nelson, Gregory A. Newby, Mustafa Sahin, Mark J. Osborn, Jonathan S. Weissman, Britt Adamson, David R. Liu
Summary: The study found that DNA mismatch repair (MMR) hinders prime editing and promotes undesired byproducts, but the efficiency of substitution, small insertion, and small deletion edits can be enhanced by developing PE4 and PE5 prime editing systems. Strategic silent mutations near the intended edit and optimization of prime editor protein also contribute to improved editing outcomes.
Article
Biochemistry & Molecular Biology
Francesco Aulicino, Martin Pelosse, Christine Toelzer, Julien Capin, Erwin Ilegems, Parisa Meysami, Ruth Rollarson, Per-Olof Berggren, Mark Simon Dillingham, Christiane Schaffitzel, Moin A. Saleem, Gavin Welsh, Imre Berger
Summary: This article addresses the challenge of delivering multiple components into living cells for precise gene-editing. The researchers utilize baculovirus, which has a high cargo capacity, to successfully replace multiple exons and restore protein expression in cells derived from patients with nephrotic syndrome. The study also demonstrates the efficient search and replace of DNA without detectable indels.
NUCLEIC ACIDS RESEARCH
(2022)
Article
Biotechnology & Applied Microbiology
Yuan Zong, Yijing Liu, Chenxiao Xue, Boshu Li, Xiangyang Li, Yanpeng Wang, Ji Li, Guanwen Liu, Xingxu Huang, Xiaofeng Cao, Caixia Gao
Summary: In this study, we have improved the editing efficiency of prime editing by engineering the structure of the prime editor and combining it with specific guide RNAs. The optimized prime editor showed significantly increased editing efficiency in plant cells, and when combined with engineered guide RNAs, it resulted in the generation of herbicide-tolerant rice plants.
NATURE BIOTECHNOLOGY
(2022)
Article
Biotechnology & Applied Microbiology
Steven Erwood, Teija M. Bily, Jason Lequyer, Joyce Yan, Nitya Gulati, Reid A. Brewer, Liangchi Zhou, Laurence Pelletier, Evgueni A. Ivakine, Ronald D. Cohn
Summary: This study demonstrates the use of the CRISPR prime editing method for high-throughput variant classification and functional characterization. The results show that the method is efficient and accurate, and can be applied to other genes with appropriate cellular assays.
NATURE BIOTECHNOLOGY
(2022)
Review
Genetics & Heredity
Peter J. Chen, David R. Liu
Summary: In this review, the authors discuss the latest developments in prime editing systems, highlighting improvements in editing efficiency and capabilities, as well as emerging applications in research and preclinical therapeutic studies. Prime editors offer versatility, specificity, and precision in making targeted DNA changes in living cells. The review summarizes prime editing strategies, addresses their limitations, discusses recent developments to overcome these limitations, and explores potential applications and future directions.
NATURE REVIEWS GENETICS
(2023)
Article
Multidisciplinary Sciences
Reto Eggenschwiler, Thomas Gschwendtberger, Christian Felski, Christopher Jahn, Florian Langer, Jared Sterneckert, Andreas Hermann, Jonathan Luehmann, Doris Steinemann, Alexandra Haase, Ulrich Martin, Susanne Petri, Tobias Cantz
Summary: CRISPR prime-editors are novel tools for genome editing, offering a versatile alternative to existing approaches. Proper expression levels and optimized transfection protocols are crucial for editing efficiency. The study demonstrates the effectiveness of piggyBac prime-editing in hiPSCs, showing over 50% editing efficiency and the ability to estimate pegRNA effectiveness quickly. Overall, the study presents a robust prime-editing toolbox for efficient genome editing in various cell lines.
SCIENTIFIC REPORTS
(2021)
Article
Biochemistry & Molecular Biology
Karthikeyan Ponnienselvan, Pengpeng Liu, Thomas Nyalile, Sarah Oikemus, Stacy A. Maitland, Nathan D. Lawson, Jeremy Luban, Scot A. Wolfe
Summary: This study demonstrates that the length of the primer binding site (PBS) and the interaction between the PBS and the spacer sequence affects the efficiency of prime editing using ribonucleoprotein complexes. By reducing the complementarity between the PBS-spacer region, the auto-inhibitory interaction can be destabilized and prime editing efficiency is enhanced. In mammalian cells, a shorter PBS length with a PBS-target strand melting temperature near 37 degrees C is optimal for prime editing.
NUCLEIC ACIDS RESEARCH
(2023)
Article
Biochemistry & Molecular Biology
V. Edwin Hillary, S. Antony Ceasar
Summary: The CRISPR/Cas system has revolutionized genetic research in the life sciences, offering various genome editing tools for engineering diverse organisms. The recently introduced prime editing system allows precise genome editing with fewer off-target effects compared to traditional CRISPR-based systems. This review presents the mechanism and applications of prime editing in plants and mammalian cells, discussing its advantages, limitations, and potential future applications.
Article
Multidisciplinary Sciences
Roman M. Doll, Michael Boutros, Fillip Port
Summary: The researchers developed optimized C-to-T base editing systems for precise alleles generation in Drosophila, and temperature was found to be a crucial parameter for efficiency. They discovered that a variant of APOBEC1 deaminase had reduced activity and considerable dose-dependent toxicity at 18 to 29 degrees Celsius. On the other hand, the temperature-tolerant evoCDA1 domain showed high editing efficiency and better tolerance. Formation of undesired mutations was exceptionally rare in Drosophila compared to other species.
Article
Biotechnology & Applied Microbiology
Jessie R. Davis, Samagya Banskota, Jonathan M. Levy, Gregory A. Newby, Xiao Wang, Andrew V. Anzalone, Andrew T. Nelson, Peter J. Chen, Andrew D. Hennes, Meirui An, Heejin Roh, Peyton B. Randolph, Kiran Musunuru, David R. Liu
Summary: Efficient methods for delivering prime editors (PEs) in vivo are needed to realize the promise of prime editing for the study and treatment of genetic disorders. This study describes the identification of bottlenecks limiting adeno-associated virus (AAV)-mediated prime editing in vivo and the development of AAV-PE vectors with increased efficiency. The optimized PE-AAV systems support high levels of in vivo prime editing and enable therapeutically relevant editing in mouse organs.
NATURE BIOTECHNOLOGY
(2023)
Article
Ophthalmology
Yuhong Chen, Xinyue Zhu, Fuxiang Ye, Hong Wang, Xiaoling Wan, Ting Zhang, Yuwei Wang, Yimin Wang, Xiaohuan Zhao, Xinyue Bai, Yushu Xiao, Xiaodong Sun
Summary: This study established a novel CNV mouse model by subretinally injecting MDA-modified POS, which simulates the AMD pathological process. Results showed that MDA-modified POS induced CNV and RPE atrophy, increased VEGF expression, disrupted RPE cell junctions, and caused autophagy-lysosomal impairment in RPE cells.
TRANSLATIONAL VISION SCIENCE & TECHNOLOGY
(2022)
Article
Medicine, General & Internal
Yifan Zhou, Yanping Hu, Jianfeng Luo, Yinwen Li, Haiyun Liu, Xiaodong Sun, Minwen Zhou
Summary: The study found that hearing loss and dual sensory loss are significantly associated with falls among middle-aged and older Chinese population, while vision loss is not significantly associated. Baseline hearing loss and dual sensory loss are related to the prevalence of falls, and the persistence of sensory loss status is also associated with falls incidence.
FRONTIERS IN MEDICINE
(2022)
Article
Cell Biology
Yafang Wang, Yang Liu, Shu Liu, Xiaomeng Li, Xinxin Liu, Ming Jiao, Yuqin Yang, Xueting Luo, Fenghua Wang, Xiaoling Wan, Xiaodong Sun
Summary: This study generated a new Cyp4v3(-/-) mouse model using CRISPR/Cas9 technology to investigate the pathogenesis of Bietti crystalline dystrophy (BCD). The model effectively exhibited age-related progression that mimicked human ocular phenotypes, and identified abnormal lipid metabolism, inflammation activation and oxidative stress caused by Cyp4v3 defect. The study demonstrated that this model could serve as a useful tool for evaluating the effect of drugs and gene therapy in BCD.
DISEASE MODELS & MECHANISMS
(2022)
Article
Biochemistry & Molecular Biology
Yumeng Zhang, Zhenzhen Zhao, Xiaohuan Zhao, Hai Xie, Chaoyang Zhang, Xiaodong Sun, Jingfa Zhang
Summary: Oxidative stress plays a key role in retinal degenerative diseases, and the exact function of HMGB2 in these diseases is still unknown. This study found that HMGB2 expression increased in the retina after light exposure and was released into the cytoplasm. In cell experiments, HMGB2 inhibited the expression of antioxidant proteins Nrf2 and HO-1 and induced pyroptosis-related signaling pathway. Further experiments showed that silencing HMGB2 increased cell viability and protected photoreceptors in a mouse model.
FREE RADICAL BIOLOGY AND MEDICINE
(2022)
Article
Cell Biology
Shiqi Yang, Tong Li, Huixun Jia, Min Gao, Yiming Li, Xiaoling Wan, Zhen Huang, Min Li, Yuanqi Zhai, Xiaomeng Li, Xiaotong Yang, Tao Wang, Jian Liang, Qing Gu, Xueting Luo, Lei Qian, Shujie Lu, Junjian Liu, Yanping Song, Fenghua Wang, Xiaodong Sun, Dechao Yu
Summary: Antiangiogenesis therapies targeting VEGF have revolutionized the treatment of neovascular ocular diseases. This study reports the preclinical assessment and phase 1 clinical outcomes of a bispecific fusion protein, efdamrofusp alfa, which showed superior efficacy over anti-VEGF monotherapy in a mouse model. These findings suggest that efdamrofusp alfa may be effective for treating neovascular ocular diseases.
SCIENCE TRANSLATIONAL MEDICINE
(2022)
Article
Medicine, General & Internal
Xiaohuan Zhao, Wenjia Liu, Bing Lu, Xinyue Zhu, Minwen Zhou, Xiaodong Sun
Summary: This study analyzed data from the China Health and Retirement Longitudinal Study and found a longitudinal association between visual impairment and depression among adults in China. The more severe the visual impairment, the greater the increase in depression scores over time. Furthermore, the relationship between visual impairment and depression was significant across different age groups.
Review
Immunology
Huimin Zhong, Xiaodong Sun
Summary: Retinal degenerative diseases and central neurodegenerative diseases share the common feature of chronic neuroinflammation. Interleukin-17A (IL-17A) plays a crucial role in human retinal degenerative diseases. This review provides an overview of the role of IL-17A in the pathogenesis of retinal degenerative diseases.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Ophthalmology
Ke Shi, Xinxin Li, Jingfa Zhang, Xiaodong Sun
Summary: This study established and validated a prognostic prediction model for uveal melanoma (UM) based on metabolism-related genes. The model accurately predicted the prognosis of UM patients and facilitated the evaluation of survival probability.
TRANSLATIONAL VISION SCIENCE & TECHNOLOGY
(2022)
Article
Chemistry, Physical
Jiao Wu, Mengqiao Xu, Wanshan Liu, Yida Huang, Ruimin Wang, Wei Chen, Lei Feng, Ning Liu, Xiaodong Sun, Minwen Zhou, Kun Qian
Summary: Using machine learning of tear metabolic fingerprinting, glaucoma can be diagnosed and monitored noninvasively and quickly. A biomarker panel for glaucoma characterization, including screening, subtyping, and early diagnosis, has been constructed.
Article
Biochemistry & Molecular Biology
Xinshuo Jia, Yanan Li, Teng Wang, Lulu Bi, Lijuan Guo, Ziting Chen, Xia Zhang, Shasha Ye, Jia Chen, Bei Yang, Bo Sun
Summary: EXD2 is a newly discovered exonuclease that has limited activity in cleaving double-stranded DNA, but displays both exoribonuclease and exodeoxyribonuclease activities towards RNA-DNA hybrids with a preference for RNA. The cleavage of hybrids by EXD2 proceeds in a discrete stepwise pattern, with a sudden duplex unwinding increment and subsequent dwell constituting a complete hydrolysis cycle.
Article
Biology
Jiangchao Xiang, Jie Su, Qiaoshuai Lan, Wenwen Zhao, Yu Zhou, Youwei Xu, Jun Niu, Shuai Xia, Qilian Qi, Sachdev Sidhu, Lu Lu, Shane Miersch, Bei Yang
Summary: Understanding the antigenic signatures of human coronaviruses is crucial for vaccine development. Researchers have identified antigenic sites in the S proteins of HCoV-229E and HCoV-NL63, which may serve as targets for pan-alpha-HCoVs vaccines. They have also discovered a neutralizing antibody that targets the connector domain, representing the first S2-directed neutralizing antibody against alpha-HCoVs. These findings provide insights into the antigenic landscape of alpha-HCoVs S proteins and the challenges and opportunities in pan-HCoV vaccine design.
COMMUNICATIONS BIOLOGY
(2022)
Article
Multidisciplinary Sciences
Jun Niu, Qi Wang, Wenwen Zhao, Bing Meng, Youwei Xu, Xianfang Zhang, Yi Feng, Qilian Qi, Yanling Hao, Xuan Zhang, Ying Liu, Jiangchao Xiang, Yiming Shao, Bei Yang
Summary: This study explores the unique features of envelope glycoproteins from prevalent HIV-1 subtypes in Asia, CRF01_AE and CRF07_BC, and their association with resistance to certain neutralizing antibodies. The authors also determine the epitope and mechanism of a neutralizing antibody from individuals infected with CRF01_AE. These findings provide valuable insights for the design of an immunofocusing HIV-1 vaccine.
NATURE COMMUNICATIONS
(2023)
Article
Medicine, Research & Experimental
Wenwen Zhao, Jifang Li, Xiao Wang, Wei Xu, Bao-Qing Gao, Jiangchao Xiang, Yaofeng Hou, Wei Liu, Jing Wu, Qilian Qi, Jia Wei, Xiaoyu Yang, Lu Lu, Li Yang, Jia Chen, Bei Yang
Summary: The spike protein of SARS-CoV-2 uses the host ACE2 receptor for entry and is the key target for vaccine development. However, new subvariants BQ.1 and XBB of Omicron have evolved with mutations in their spike proteins, reducing the efficacy of current vaccines. In contrast, targeting the host ACE2 receptor offers an alternative antiviral strategy that is more resistant to viral evolution and can provide broad prevention against related coronaviruses.