Article
Biochemistry & Molecular Biology
Daqi Yan, Bin Ren, Lang Liu, Fang Yan, Shaofang Li, Guirong Wang, Wenxian Sun, Xueping Zhou, Huanbin Zhou
Summary: The study investigated the activities of three evolved E. coli adenosine deaminase TadA variants in transgenic rice, revealing that TadA8e outperformed TadA8.17 and TadA8.20. The newly generated variant TadA9, with V82S/Q154R mutations, showed broad compatibility and efficient editing in various CRISPR systems. These novel ABEs have great potential in the development of plant base editors and crop molecular breeding.
Article
Veterinary Sciences
Federico Caso, Benjamin Davies
Summary: Genome editing using programmable RNA-dependent Cas endonucleases has significantly improved efficiency and precision in targeted genomic changes, particularly through advancements like base editing. Despite limitations in possible base conversions, recent development in prime editing may offer a solution to expand the range of genome manipulations in laboratory animal research.
LABORATORY ANIMALS
(2022)
Review
Genetics & Heredity
Elena Piotter, Michelle E. McClements, Robert E. MacLaren
Summary: Stargardt macular dystrophy (STGD1) is a common inherited childhood blindness with no current treatments. This study demonstrates the potential of DNA base editing approaches, such as CRISPR-Cas, for targeting pathogenic mutations in ABCA4 gene and provides insights into the genetic landscape of Stargardt.
FRONTIERS IN GENETICS
(2022)
Article
Biochemistry & Molecular Biology
Simon Sretenovic, Desuo Yin, Adam Levav, Jeremy D. Selengut, Stephen M. Mount, Yiping Qi
Summary: This study presents a new plant genome-editing system based on the hybrid iSpyMacCas9 platform, allowing for targeted mutagenesis and base editing at A-rich PAMs. It fills a significant technology gap in the CRISPR-Cas9 system for editing NAAR PAMs in plants, greatly expanding the targeting scope of CRISPR-Cas9. The vector systems are fully compatible with Gateway cloning and existing single-guide RNA expression systems, making it easy for others to adopt.
PLANT COMMUNICATIONS
(2021)
Article
Biochemistry & Molecular Biology
Karen Mention, Kader Cavusoglu-Doran, Anya T. Joynt, Lucia Santos, David Sanz, Alice C. Eastman, Christian Merlo, Elinor Langfelder-Schwind, Martina F. Scallan, Carlos M. Farinha, Garry R. Cutting, Neeraj Sharma, Patrick T. Harrison
Summary: In this study, two gene editing strategies were evaluated for correcting W1282X variant in cystic fibrosis. Adenine Base Editing (ABE) successfully corrected W1282X but caused bystander editing at adjacent adenine. Homology-Independent Targeted Integration (HITI) enabled integration of CFTR superexon in CFTR locus, restoring CFTR function.
HUMAN MOLECULAR GENETICS
(2023)
Article
Biochemistry & Molecular Biology
Xiaorui Huang, Fei Su, Sheng Huang, Fating Mei, Xiaomu Niu, Changle Ma, Hui Zhang, Xiaoguo Zhu, Jian-Kang Zhu, Jinshan Zhang
Summary: Novel alleles of the Waxy gene, including the waxy(abe2) allele, were generated by nucleotide substitutions in the middle region of the Wx protein, leading to improvements in amylose content and cooking quality of rice grains. The waxy(abe2) allele exhibited desirable characteristics without undesirable agronomic traits, providing a promising breeding material for enhancing rice grain quality.
JOURNAL OF INTEGRATIVE PLANT BIOLOGY
(2021)
Article
Biochemical Research Methods
Abdullah, Pujie Wang, Tongren Han, Wei Liu, Wenting Ren, Yuehong Wu, Yi Xiao
Summary: This study reported the development of a highly efficient adenine base editing system for Pseudomonas species, providing molecular tools for understanding and harnessing the potential of this genus. The study also developed a prediction workflow for protein dysfunction, expanding the application of the editing system to non-model Pseudomonas species.
ACS SYNTHETIC BIOLOGY
(2022)
Article
Biology
Ding Zhao, Xun Gao, Jiale Zhou, Jinze Li, Yuqiang Qian, Di Wang, Wenchao Niu, Tao Zhang, Mingyang Hu, Haoyang Xiong, Liangxue Lai, Zhanjun Li
Summary: By engineering domain-inlaid Nme2Cas9 base editors, we have improved the editing efficiency of Nme2ABE8e, allowing for increased on-target DNA editing in mammalian cells and expanded PAM compatibility. These modifications will expand the base editing toolset for efficient gene modification and therapeutic applications.
Review
Biochemistry & Molecular Biology
Hyomin K. Lee, Yeounsun Oh, Juyoung Hong, Seung Hwan Lee, Junho K. Hur
Summary: The CRISPR system is a family of DNA sequences originally discovered in prokaryotes that has been widely used for genome editing. It induces mutations at specific genomic loci by DNA double-strand breaks, activating endogenous DNA repair systems. This system can result in deletions, insertions, and substitutions, and novel methods have been developed to achieve highly efficient and precise genome editing.
Article
Biochemistry & Molecular Biology
Huixian Hou, Mai Horikawa, Yuki Narita, Hirofumi Jono, Yutaka Kakizoe, Yuichiro Izumi, Takashige Kuwabara, Masashi Mukoyama, Hideyuki Saito
Summary: Renal fibrosis, the final manifestation of chronic kidney disease (CKD), can be controlled and prevented by targeting the enzyme SULT1A1 to decrease the accumulation of indoxyl sulfate (IS). In a study with Sult1a1-KO mice, it was found that the exacerbation of inflammation and renal fibrosis in WT mice was significantly suppressed in Sult1a1-KO mice. Expression of CD206(+) was upregulated and β-catenin expression was downregulated in Sult1a1-KO mice. Additionally, the study confirmed the beneficial effect of erythropoietin (EPO) in attenuating renal fibrosis.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Cell Biology
Xingang Yao, Pin Lyu, Kyung Yoo, Manish Kumar Yadav, Ravi Singh, Anthony Atala, Baisong Lu
Summary: A mechanism to actively enrich RNPs into EVs using RNA aptamer and aptamer-binding protein interactions has been described, resulting in efficient genome editing and transient expression. This system allows for multiplex genome editing targeting multiple loci and can deliver RNPs active in vivo. The data demonstrate that this approach could enhance genome editing efficiency and safety.
JOURNAL OF EXTRACELLULAR VESICLES
(2021)
Article
Plant Sciences
Anouchka Guyon-Debast, Alessandro Alboresi, Zoe Terret, Florence Charlot, Floriane Berthier, Pol Vendrell-Mir, Josep M. Casacuberta, Florian Veillet, Tomas Morosinotto, Jean-Luc Gallois, Fabien Nogue
Summary: CRISPR-Cas9 base editors can achieve efficient and precise single-base mutations in Physcomitrium patens, facilitating gene functional analysis and enabling the production of randomly mutagenized variants of a specific gene through multiple sgRNA base editing. The development of a co-editing selection system further enhances the efficiency of site-specific base editing in P. patens.
Article
Genetics & Heredity
Pin Lyu, Zuyan Lu, Sung-Ik Cho, Manish Yadav, Kyung Whan Yoo, Anthony Atala, Jin-Soo Kim, Baisong Lu
Summary: This study developed a delivery method to reduce RNA off-target activities of ABEs using electroporation or lentiviral capsids. These methods enabled efficient guided base editing with stable detectable RNA off-target activities. This approach makes ABE closer to possible therapeutic applications.
Article
Agriculture, Dairy & Animal Science
Yezi Kong, Chenxu Zhao, Panpan Tan, Siqi Liu, Yan Huang, Fangyuan Zeng, Pingjun Ma, Yazhou Guo, Baoyu Zhao, Jianguo Wang
Summary: During the perinatal period, dairy cows experience negative energy balance, leading to lipid mobilization and accumulation of NEFAs in the liver. FGF21 treatment can reduce TG content in the liver by 50%. This study found that FGF21 regulates lipid metabolism in bovine liver cells through the AMPK signaling pathway, affecting lipid formation, oxidation, and transport. The findings suggest that FGF21 has potential value in alleviating metabolic diseases in dairy cows.
Article
Agriculture, Dairy & Animal Science
Jiying Liu, Ruilong Song, Shengyan Su, Nannan Qi, Qifa Li, Zhuang Xie, Shali Yu
Summary: Betaine can improve fat distribution and mitochondrial function in goose liver, with a certain repairing effect in a high-glucose culture medium, reducing fatty liver damage.
Article
Cell & Tissue Engineering
Killian Hurley, Jun Ding, Carlos Villacorta-Martin, Michael J. Herriges, Anjali Jacob, Marall Vedaie, Konstantinos D. Alysandratos, Yuliang L. Sun, Chieh Lin, Rhiannon B. Werder, Jessie Huang, Andrew A. Wilson, Aditya Mithal, Gustavo Mostoslavsky, Irene Oglesby, Ignacio S. Caballero, Susan H. Guttentag, Farida Ahangari, Naftali Kaminski, Alejo Rodriguez-Fraticelli, Fernando Camargo, Ziv Bar-Joseph, Darrell N. Kotton
Article
Immunology
Jason P. Lynch, Rhiannon B. Werder, Bodie F. Curren, Md. Al Amin Sikder, Ashik Ullah, Ismail Sebina, Ridwan B. Rashid, Vivian Zhang, John W. Upham, Geoff R. Hill, Raymond J. Steptoe, Simon Phipps
MUCOSAL IMMUNOLOGY
(2020)
Article
Microbiology
Zhixuan Loh, Jennifer Simpson, Ashik Ullah, Vivian Zhang, Wan J. Gan, Jason P. Lynch, Rhiannon B. Werder, Al Amin Sikder, Katie Lane, Choon Boon Sim, Enzo Porrello, Stuart B. Mazzone, Peter D. Sly, Raymond J. Steptoe, Kirsten M. Spann, Maria B. Sukkar, John W. Upham, Simon Phipps
Article
Cell & Tissue Engineering
Jessie Huang, Adam J. Hume, Kristine M. Abo, Rhiannon B. Werder, Carlos Villacorta-Martin, Konstantinos-Dionysios Alysandratos, Mary Lou Beermann, Chantelle Simone-Roach, Jonathan Lindstrom-Vautrin, Judith Olejnik, Ellen L. Suder, Esther Bullitt, Anne Hinds, Arjun Sharma, Markus Bosmann, Ruobing Wang, Finn Hawkins, Eric J. Burks, Mohsan Saeed, Andrew A. Wilson, Elke Muhlberger, Darrell N. Kotton
Article
Biochemistry & Molecular Biology
Ryan M. Hekman, Adam J. Hume, Raghuveera Kumar Goel, Kristine M. Abo, Jessie Huang, Benjamin C. Blum, Rhiannon Bree Werder, Ellen L. Suder, Indranil Paul, Sadhna Phanse, Ahmed Youssef, Konstantinos D. Alysandratos, Dzmitry Padhorny, Sandeep Ojha, Alexandra Mora-Martin, Dmitry Kretov, Peter E. A. Ash, Mamta Verma, Jian Zhao, J. J. Patten, Carlos Villacorta-Martin, Dante Bolzan, Carlos Perea-Resa, Esther Bullitt, Anne Hinds, Andrew Tilston-Lunel, Xaralabos Varelas, Shaghayegh Farhangmehr, Ulrich Braunschweig, Julian H. Kwan, Mark McComb, Avik Basu, Mohsan Saeed, Valentina Perissi, Eric J. Burks, Matthew D. Layne, John H. Connor, Robert Davey, Ji-Xin Cheng, Benjamin L. Wolozin, Benjamin J. Blencowe, Stefan Wuchty, Shawn M. Lyons, Dima Kozakov, Daniel Cifuentes, Michael Blower, Darrell N. Kotton, Andrew A. Wilson, Elke Muhlberger, Andrew Emili
Correction
Biochemistry & Molecular Biology
Ryan M. Hekman, Adam J. Hume, Raghuveera Kumar Goel, Kristine M. Abo, Jessie Huang, Benjamin C. Blum, Rhiannon B. Werder, Ellen L. Suder, Indranil Paul, Sadhna Phanse, Ahmed Youssef, Konstantinos D. Alysandratos, Dzmitry Padhorny, Sandeep Ojha, Alexandra Mora-Martin, Dmitry Kretov, Peter E. A. Ash, Mamta Verma, Jian Zhao, J. J. Patten, Carlos Villacorta-Martin, Dante Bolzan, Carlos Perea-Resa, Esther Bullitt, Anne Hinds, Andrew Tilston-Lunel, Xaralabos Varelas, Shaghayegh Farhangmehr, Ulrich Braunschweig, Julian H. Kwan, Mark McComb, Avik Basu, Mohsan Saeed, Valentina Perissi, Eric J. Burks, Matthew D. Layne, John H. Connor, Robert Davey, Ji-Xin Cheng, Benjamin L. Wolozin, Benjamin J. Blencowe, Stefan Wuchty, Shawn M. Lyons, Dima Kozakov, Daniel Cifuentes, Michael Blower, Darrell N. Kotton, Andrew A. Wilson, Elke Muhlberger, Andrew Emili
Article
Physiology
Ruobing Wang, Adam J. Hume, Mary Lou Beermann, Chantelle Simone-Roach, Jonathan Lindstrom-Vautrin, Jake Le Suer, Jessie Huang, Judith Olejnik, Carlos Villacorta-Martin, Esther Bullitt, Anne Hinds, Mahboobe Ghaedi, Stuart Rollins, Rhiannon B. Werder, Kristine M. Abo, Andrew A. Wilson, Elke Muhlberger, Darrell N. Kotton, Finn J. Hawkins
Summary: Understanding how SARS-CoV-2 infects the airway epithelium and developing treatment strategies for COVID-19 pneumonia is crucial. iPSC-derived airway cells provide a physiologically relevant in vitro model system to study the pathogenesis of the disease and evaluate the effectiveness of treatments. The study shows that iPSC-airway cells are permissive to SARS-CoV-2 infection and demonstrate robust interferon and inflammatory responses.
AMERICAN JOURNAL OF PHYSIOLOGY-LUNG CELLULAR AND MOLECULAR PHYSIOLOGY
(2022)
Article
Critical Care Medicine
Rhiannon B. Werder, Md Ashik Ullah, Muhammed Mahfuzur Rahman, Jennifer Simpson, Jason P. Lynch, Natasha Collinson, Sonja Rittchen, Ridwan B. Rashid, Md Al Amin Sikder, Herlina Y. Handoko, Bodie F. Curren, Ismail Sebina, Gunter Hartel, Alec Bissell, Sylvia Ngo, Tejasri Yarlagadda, Sumaira Z. Hasnain, Wenying Lu, Sukhwinder S. Sohal, Megan Martin, Simon Bowler, Lucy D. Burr, Laurent O. Martinez, Bernard Robaye, Kirsten Spann, Manuel A. R. Ferreira, Simon Phipps
Summary: The study discovers P2Y(13)-R as a novel regulator of the nuclear alarmins IL-33 and HMGB1, and demonstrates that targeting this GPCR through genetic deletion or treatment with small-molecule antagonists protects against the onset and exacerbations of asthma.
AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE
(2022)
Article
Multidisciplinary Sciences
Maor Sauler, John E. McDonough, Taylor S. Adams, Neeharika Kothapalli, Thomas Barnthaler, Rhiannon B. Werder, Jonas C. Schupp, Jessica Nouws, Matthew J. Robertson, Cristian Coarfa, Tao Yang, Maurizio Chioccioli, Norihito Omote, Carlos Cosme, Sergio Poli, Ehab A. Ayaub, Sarah G. Chu, Klaus H. Jensen, Jose L. Gomez, Clemente J. Britto, Micha Sam B. Raredon, Laura E. Niklason, Andrew A. Wilson, Pascal N. Timshel, Naftali Kaminski, Ivan O. Rosas
Summary: Chronic obstructive pulmonary disease (COPD) is a leading cause of death worldwide, but our understanding of cell-specific mechanisms underlying COPD pathobiology remains incomplete. In this study, the authors used single-cell RNA sequencing to analyze human lung tissue and identified transcriptional changes in alveolar niche cells associated with the disease.
NATURE COMMUNICATIONS
(2022)
Article
Medicine, Research & Experimental
Kristine M. Abo, Julio Sainz de Aja, Jonathan Lindstrom-Vautrin, Konstantinos-Dionysios Alysandratos, Alexsia Richards, Carolina Garcia-de-Alba, Jessie Huang, Olivia T. Hix, Rhiannon B. Werder, Esther Bullitt, Anne Hinds, Isaac Falconer, Carlos Villacorta-Martin, Rudolf Jaenisch, Carla F. Kim, Darrell N. Kotton, Andrew A. Wilson
Summary: Type 2 alveolar epithelial cells (AT2s) play a vital role in the biology of the distal lung. In vitro model systems can help understand the functional characteristics of AT2s in homeostasis and disease. The study found that iAT2s cultured at air-liquid interface (ALI) maintained an AT2 phenotype and upregulated expression of transcripts associated with AT2 maturation. The effects of exposure to inhaled toxicants were also assessed.
Article
Multidisciplinary Sciences
Rhiannon B. Werder, Tao Liu, Kristine M. Abo, Jonathan Lindstrom-Vautrin, Carlos Villacorta-Martin, Jessie Huang, Anne Hinds, Nathan Boyer, Esther Bullitt, Marc Liesa, Edwin K. Silverman, Darrell N. Kotton, Michael H. Cho, Xiaobo Zhou, Andrew A. Wilson
Summary: This study used CRISPR interference to investigate the function of genes associated with COPD in induced pluripotent stem cell-derived type 2 alveolar epithelial cells. The results showed that these genes affect the differentiation, maturation, and proliferation of cells. Detailed characterization of the DSP gene revealed its role in regulating cell-cell junctions, proliferation, mitochondria function, and response to cigarette smoke-induced injury.
Article
Cell Biology
Joseph E. Kaserman, Rhiannon B. Werder, Feiya Wang, Taylor Matte, Michelle I. Higgins, Mark Dodge, Jonathan Lindstrom-Vautrin, Pushpinder Bawa, Anne Hinds, Esther Bullitt, Ignacio S. Caballero, Xu Shi, Robert E. Gerszten, Nicola Brunetti-Pierri, Marc Liesa, Carlos Villacorta-Martin, Anthony N. Hollenberg, Darrell N. Kotton, Andrew A. Wilson
Summary: Individuals homozygous for the Zmutation in alpha-1 antitrypsin deficiency are at increased risk for liver disease. Heterozygous individuals also have a degree of risk. Lack of model systems has limited the study of the impact of a single Z alpha-1 antitrypsin (ZAAT) allele on hepatocyte biology. This study successfully derived syngeneic induced pluripotent stem cells (iPSCs) to investigate the effects of ZAAT heterozygosity in iPSC-hepatocytes (iHeps), finding that MZ heterozygous iHeps exhibit an intermediate disease phenotype and share certain alterations with ZZ iHeps.
Meeting Abstract
Critical Care Medicine
R. Werder, M. H. Cho, A. X. Zhou, D. N. Kotton, A. A. Wilson
AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE
(2021)
Article
Medicine, Research & Experimental
Kim Vanuytsel, Aditya Mithal, Richard M. Giadone, Anthony K. Yeung, Taylor M. Matte, Todd W. Dowrey, Rhiannon B. Werder, Gregory J. Miller, Nancy S. Miller, Christopher D. Andry, George J. Murphy