Article
Biotechnology & Applied Microbiology
Francisco J. Sanchez-Rivera, Bianca J. Diaz, Edward R. Kastenhuber, Henri Schmidt, Alyna Katti, Margaret Kennedy, Vincent Tem, Yu-Jui Ho, Josef Leibold, Stella Paffenholz, Francisco M. Barriga, Kevan Chu, Sukanya Goswami, Alexandra N. Wuest, Janelle M. Simon, Kaloyan M. Tsanov, Debyani Chakravarty, Hongxin Zhang, Christina S. Leslie, Scott W. Lowe, Lukas E. Dow
Summary: Improved base editing libraries enable high-throughput functional analysis of single-nucleotide variants in cancer. A modular base-editing-activity sensor was developed to measure the editing efficiency and precision of thousands of sgRNAs paired with functionally distinct base editors. This comprehensive resource of sgRNAs can be used to study cancer-associated single nucleotide variants in cell and animal models.
NATURE BIOTECHNOLOGY
(2022)
Article
Oncology
Sho Mizuno, Masachika Ikegami, Takafumi Koyama, Kuniko Sunami, Dai Ogata, Hidenori Kage, Mitsuru Yanagaki, Hiroshi Ikeuchi, Toshihide Ueno, Michihiro Tanikawa, Katsutoshi Oda, Yutaka Osuga, Hiroyuki Mano, Shinji Kohsaka
Summary: This study evaluated the transforming potential and drug sensitivity of 100 different MAP2K1 variants, finding 16 of them to be oncogenic. The sensitivity to BRAF inhibitors was associated with the RAF dependency of the MAP2K1 variants, while the synergistic effect of BRAF and MEK inhibitors was observed in RAF-regulated and RAF-dependent variants. Individual functional analysis is important for selecting optimal treatments for patients with MAP2K1 variants.
MOLECULAR CANCER THERAPEUTICS
(2023)
Article
Medicine, Research & Experimental
Carlos G. Vanoye, Reshma R. Desai, Zhigang Ji, Sneha Adusumilli, Nirvani Jairam, Nora Ghabra, Nishtha Joshi, Eryn Fitch, Katherine L. Helbig, Dianalee McKnight, Amanda S. Lindy, Fanggeng Zou, Ingo Helbig, Edward C. Cooper, Alfred L. George
Summary: This study investigated the functional and pharmacological properties of numerous KCNQ2 gene variants using automated patch clamp recordings. The results showed that most disease-associated KCNQ2 variants exhibited prominent loss-of-function with dominant-negative effects, providing strong evidence for their pathogenicity. Additionally, the response of KCNQ2 variants to retigabine, a proposed precision therapy, varied depending on the genotype.
Article
Chemistry, Multidisciplinary
Jianan Li, Jianxiang Lin, Shisheng Huang, Min Li, Wenxia Yu, Yuting Zhao, Junfan Guo, Pumin Zhang, Xingxu Huang, Yunbo Qiao
Summary: Selective inhibition of protein kinases is a promising therapeutic approach for cancer treatment, but it often leads to drug resistance. This study utilized CRISPR-based base editors to identify functional phosphorylation sites associated with 5-fluorouracil (5-FU) resistance in colorectal cancer cells. The results revealed downstream substrates of RSK2 and PAK4 kinases that play a crucial role in response to 5-FU chemotherapy, suggesting that targeting these kinases in combination with 5-FU could effectively inhibit cell growth and induce apoptosis.
Article
Biotechnology & Applied Microbiology
Cristina Vieitez, Bede P. Busby, David Ochoa, Andre Mateus, Danish Memon, Marco Galardini, Umut Yildiz, Matteo Trovato, Areeb Jawed, Alexander G. Geiger, Michaela Oborska-Oplova, Clement M. Potel, Sibylle C. Vonesch, Chelsea Szu Tu, Mohammed Shahraz, Frank Stein, Lars M. Steinmetz, Vikram G. Panse, Kyung-Min Noh, Mikhail M. Savitski, Athanasios Typas, Pedro Beltrao
Summary: Phosphorylation plays a critical role in regulating various cellular processes, but functional annotations for the majority of discovered phosphosites are lacking. A chemical genetic approach was used to study the functional relevance of phosphosites in yeast, revealing potential functional significance for 42% of the sites. This high-throughput method allows for the functional characterization of individual phosphosites at scale.
NATURE BIOTECHNOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Sateesh Krishnamurthy, Soumba Traore, Ashley L. Cooney, Christian M. Brommel, Katarina Kulhankova, Patrick L. Sinn, Gregory A. Newby, David R. Liu, Paul B. McCray
Summary: The study found that using adenine base editor RNPs can successfully correct certain gene mutations causing CF, with repair efficiencies reaching 38-82%, achieving functional correction of CFTR-dependent channel activity.
NUCLEIC ACIDS RESEARCH
(2021)
Article
Multidisciplinary Sciences
Benjamin Neveu, Chantal Richer, Pauline Cassart, Maxime Caron, Camille Jimenez-Cortes, Pascal St-Onge, Claire Fuchs, Nicolas Garnier, Stephane Gobeil, Daniel Sinnett
Summary: ETV6 transcriptional activity is crucial for blood cell development, but its regulatory network is still unknown. We identified genes that modulate ETV6 repressive transcriptional activity and revealed their role in cellular transformation.
Article
Multidisciplinary Sciences
Siwei Li, Jingjing An, Yaqiu Li, Xiagu Zhu, Dongdong Zhao, Lixian Wang, Yonghui Sun, Yuanzhao Yang, Changhao Bi, Xueli Zhang, Meng Wang
Summary: This study developed an automated high-throughput platform for efficient generation of cell disease models with pathogenic SNVs. A learning model was also developed to predict the performance of gene editing based on chromatin accessibility and context-sequence information. This work is expected to accelerate the development of gene therapies.
NATURE COMMUNICATIONS
(2022)
Article
Biotechnology & Applied Microbiology
Qiurong Ren, Simon Sretenovic, Guanqing Liu, Zhaohui Zhong, Jiaheng Wang, Lan Huang, Xu Tang, Yachong Guo, Li Liu, Yuechao Wu, Jie Zhou, Yuxin Zhao, Han Yang, Yao He, Shishi Liu, Desuo Yin, Rocio Mayorga, Xuelian Zheng, Tao Zhang, Yiping Qi, Yong Zhang
Summary: In this study, the A3A/Y130F-CBE_V01 was identified as the most efficient C-to-T base editor in plants, showing applications in generating microRNA-resistant mRNA transcripts and herbicide-resistant allele evolution in rice. Additionally, the development and testing of multiple CBE_V02, CBE_V03, and CBE_V04 systems in rice protoplasts demonstrated improved editing activity and purity, with the CBE_V04 systems showing enhanced editing efficiency through focal recruitment of uracil DNA glycosylase inhibitors by engineered sgRNA scaffolds. Whole-genome sequencing revealed varying levels of off-target effects among different CBE systems, with PmCDA1-CBE_V04 and A3A/Y130F-CBE_V04 identified as high-efficiency, high-purity, and highly specific next-generation plant CBEs.
PLANT BIOTECHNOLOGY JOURNAL
(2021)
Article
Cell Biology
Hellen Weinschutz Mendes, Uma Neelakantan, Yunqing Liu, Sarah E. Fitzpatrick, Tianying Chen, Weimiao Wu, April Pruitt, David S. Jin, Priyanka Jamadagni, Marina Carlson, Cheryl M. Lacadie, Kristen D. Enriquez, Ningshan Li, Dejian Zhao, Sundas Ijaz, Catalina Sakai, Christina Szi, Brendan Rooney, Marcus Ghosh, Ijeoma Nwabudike, Andrea Gorodezky, Sumedha Chowdhury, Meeraal Zaheer, Sarah McLaughlin, Joseph M. Fernandez, Jia Wu, Jeffrey A. Eilbott, Brent Vander Wyk, Jason Rihel, Xenophon Papademetris, Zuoheng Wang, Ellen J. Hoffman
Summary: This study performs parallel in vivo functional analysis of 10 ASD genes at the behavioral, structural, and circuit levels in zebrafish mutants, revealing both unique and overlapping effects of gene loss of function. Whole-brain mapping identifies the forebrain and cerebellum as the most significant contributors to brain size differences, while regions involved in sensory-motor control, particularly dopaminergic regions, are associated with altered baseline brain activity. Finally, a global increase in microglia resulting from ASD gene loss of function in select mutants implicates neuroimmune dysfunction as a key pathway relevant to ASD biology.
Article
Biochemistry & Molecular Biology
Irene Beusch, Beiduo Rao, Michael K. Studer, Tetiana Luhovska, Viktorija Sukyte, Susan Lei, Juan Oses-Prieto, Em SeGraves, Alma Burlingame, Stefanie Jonas, Hiten D. Madhani
Summary: The spliceosome is a complex machine with 5 snRNAs and >150 proteins. Haploid CRISPR-Cas9 base editing was used to target the human spliceosome, and mutants were investigated using the U2 snRNP/SF3b inhibitor, pladienolide B. The study identified functional sites and resistance substitutions in the spliceosome, and discovered DHX15/hPrp43 as the ATPase ligand for SUGP1.
Review
Medicine, Research & Experimental
Kamran Hosseini, Maryam Ranjbar, Abbas Pirpour Tazehkand, Parina Asgharian, Soheila Montazersaheb, Vahideh Tarhriz, Tohid Ghasemnejad
Summary: Clinical oncologists require reliable and non-invasive biomarkers to monitor cancer patients. Extracellular vesicles, particularly exosomes, have emerged as valuable sources of tumor markers, offering stable molecular and genetic contents that can be detected in various body fluids.
JOURNAL OF TRANSLATIONAL MEDICINE
(2022)
Article
Multidisciplinary Sciences
Gou Takahashi, Daiki Kondo, Minato Maeda, Yuji Morishita, Yuichiro Miyaoka
Summary: This study utilized the Single Particle isolation System to analyze genome editing outcomes in individual human cultured cells, revealing a binary nature of genome editing induction and providing a new strategy for analyzing genome editing outcomes in single cells.
Article
Cell Biology
Fang Cao, Yunpeng Jiang, Lin Chang, Hongzhen Du, De Chang, Chunxiao Pan, Xiaozheng Huang, Donglin Yu, Mi Zhang, Yongna Fan, Xiaocui Bian, Kailong Li
Summary: Pancreatic cancer is characterized by early metastasis and limited response to current therapies. Through a genetic screening platform, YWHAZ has been identified as a key regulator of pancreatic cancer metastasis. Overexpression of YWHAZ promotes cell migration and invasion, and is associated with poor prognosis in pancreatic cancer patients.
CELL DEATH & DISEASE
(2023)
Article
Computer Science, Information Systems
Yuyi Sun, Jiming Chen, Shibo He, Zhiguo Shi
Summary: The study proposes a heterogeneous redundant coverage solution to meet the requirements of different end devices in a hybrid LoRa network, while considering the impact of spreading factors on system performance. By establishing system performance models and analyzing system throughput and energy efficiency, simulation results show that this solution gains more system throughput and energy efficiency compared to a single-coverage solution.
IEEE INTERNET OF THINGS JOURNAL
(2021)
Article
Engineering, Biomedical
Hyewon Jang, Dong Hyun Jo, Chang Sik Cho, Jeong Hong Shin, Jung Hwa Seo, Goosang Yu, Ramu Gopalappa, Daesik Kim, Sung-Rae Cho, Jeong Hun Kim, Hyongbum Henry Kim
Summary: Prime editing has shown the potential to precisely correct disease-causing mutations and ameliorate disease phenotypes in mouse models of genetic diseases. By identifying optimal guide RNAs, it can precisely target genes without detectable off-target edits. However, further validation in more animal models is necessary.
NATURE BIOMEDICAL ENGINEERING
(2022)
Review
Medicine, General & Internal
Jung Min Lim, Hyongbum Henry Kim
Summary: This review explores the advances and applications of CRISPR-based genome editing, explaining the basic principles and mechanisms of CRISPR-based genome editing along with recent clinical trials and animal studies. Despite some concerns over efficacy and safety, CRISPR-based genome editing holds great potential in clinical practice.
YONSEI MEDICAL JOURNAL
(2022)
Article
Pharmacology & Pharmacy
Kyemyung Park, Yukyung Kim, Mijeong Son, Dongwoo Chae, Kyungsoo Park
Summary: A model was developed to describe the temporal changes of absolute neutrophil count in non-small cell lung cancer patients receiving chemotherapy and G-CSF treatment. The model showed reasonable goodness of fit and parameter estimates, which can help identify risk and suggest dose reduction.
Article
Medicine, Research & Experimental
Dongwoo Chae, Na Young Kim, Hyun Joo Kim, Tae Lim Kim, Su Jeong Kang, So Yeon Kim
Summary: This study aimed to develop a risk scoring system for predicting 1-week and 1-month mortality after major non-cardiac surgery, and investigate the impact of postoperative factors on mortality. The results showed that incorporating postoperative information significantly improved the predictive performance for 1-month mortality, while the effect on predicting 1-week mortality was minimal.
CTS-CLINICAL AND TRANSLATIONAL SCIENCE
(2022)
Article
Health Care Sciences & Services
Sujung Park, Kyemyung Park, Jae Geun Lee, Tae Yang Choi, Sungtaik Heo, Bon-Nyeo Koo, Dongwoo Chae
Summary: This study developed machine learning models and a scoring system to predict massive hemorrhage in liver transplantation. Factors such as disease etiology, aPTT, and operation duration were found to be important predictors.
JOURNAL OF PERSONALIZED MEDICINE
(2022)
Review
Ophthalmology
Dong Hyun Jo, Sangsu Bae, Hyongbum Henry Kim, Jin-Soo Kim, Jeong Hun Kim
Summary: Inherited retinal diseases (IRDs) are vision-threatening retinal disorders caused by gene variants related to vision. Current treatment options are limited, but genome editing using CRISPR-Cas9 technologies shows promise for correcting pathogenic variants and providing new treatment opportunities.
PROGRESS IN RETINAL AND EYE RESEARCH
(2023)
Article
Multidisciplinary Sciences
Seungho Jung, Kyemyung Park, Kyong Ihn, Seon Ju Kim, Myoung Soo Kim, Dongwoo Chae, Bon-Nyeo Koo
Summary: This study aimed to develop an individualized predictive model for 90-day graft failure in pediatric liver transplantation using machine learning methods. The model showed superior discrimination power and provided valuable information for clinicians in postoperative management.
SCIENTIFIC REPORTS
(2022)
Article
Biochemistry & Molecular Biology
Goosang Yu, Hui Kwon Kim, Jinman Park, Hyunjong Kwak, Yumin Cheong, Dongyoung Kim, Jiyun Kim, Jisung Kim, Hyongbum Henry Kim
Summary: In this study, the efficiency of prime editing was evaluated for a large number of pegRNAs. Computational models, DeepPrime and DeepPrime-FT, were developed to predict editing efficiencies for different prime editing systems and cell types. The study also included profiling of editing efficiencies at mismatched targets and the development of a computational model for predicting editing efficiencies at such targets. These findings and models will greatly enhance the applications of prime editing.
Article
Biotechnology & Applied Microbiology
Nahye Kim, Sungchul Choi, Sungjae Kim, Myungjae Song, Jung Hwa Seo, Seonwoo Min, Jinman Park, Sung-Rae Cho, Hyongbum Henry Kim
Summary: A deep learning model is used to predict the best base editor for specific applications. Seven base editors and nine Cas9 variants were systematically compared to determine their editing windows, outcomes, and preferred motifs. Two computational models, DeepCas9variants and DeepBE, were developed to predict the efficiency and outcomes of base editors, resulting in significantly higher efficiency for DeepBE-designed editors compared to rational design.
NATURE BIOTECHNOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Young-hoon Kim, Nahye Kim, Ikenna Okafor, Sungchul Choi, Seonwoo Min, Joonsun Lee, Seung-Min Bae, Keunwoo Choi, Janice Choi, Vinayak Harihar, Youngho Kim, Jin-Soo Kim, Benjamin P. Kleinstiver, Jungjoon K. Lee, Taekjip Ha, Hyongbum Henry Kim
Summary: Researchers have developed an improved version of Sniper-Cas9, called Sniper2L, which combines high specificity with retained high activity for efficient and specific genome editing at a large number of target sequences.
NATURE CHEMICAL BIOLOGY
(2023)
Article
Biochemical Research Methods
Sang-Yeon Seo, Seonwoo Min, Sungtae Lee, Jung Hwa Seo, Jinman Park, Hui Kwon Kim, Myungjae Song, Dawoon Baek, Sung-Rae Cho, Hyongbum Henry Kim
Summary: This study compares the effectiveness of 17 small Cas9s and provides guidance for researchers to select the most suitable small Cas9 for specific target sequences.
Article
Biology
Jung Hwa Seo, Jeong Hong Shin, Junwon Lee, Daesik Kim, Hye-Yeon Hwang, Bae-Geun Nam, Jinu Lee, Hyongbum Henry Kim, Sung-Rae Cho
Summary: The use of CRISPR interference (CRISPRi) can repress the expression of mutant huntingtin while preserving wild-type huntingtin, potentially delaying disease progression in Huntington's disease, which is caused by a CAG repeat expansion in the huntingtin gene.
COMMUNICATIONS BIOLOGY
(2023)
Article
Medicine, Research & Experimental
Byunghwa Noh, John Hoon Rim, Ramu Gopalappa, Haiyue Lin, Kyu Min Kim, Min Jin Kang, Heon Yung Gee, Jae Young Choi, Hyongbum Henry Kim, Jinsei Jung
Summary: In vivo gene editing targeting outer hair cells using a dual adeno-associated virus package significantly improved auditory thresholds and a new live-cell imaging technique demonstrated the enhanced activity of KCNQ4 channels after disruption of mutant allele. These findings support the development of targeted therapies for DFNA2 and the potential use of CRISPR-based gene therapy to rectify defects in outer hair cells.