Article
Multidisciplinary Sciences
I. F. Schene, I. P. Joore, J. H. L. Baijens, R. Stevelink, G. Kok, S. Shehata, E. F. Ilcken, E. C. M. Nieuwenhuis, D. P. Bolhuis, R. C. M. van Rees, S. A. Spelier, H. P. J. van der Doef, J. M. Beekman, R. H. J. Houwen, E. E. S. Nieuwenhuis, S. A. Fuchs
Summary: This study presents a fluorescent prime editing and enrichment reporter (fluoPEER) system to evaluate the efficiency of pegRNAs and prime editor variants. The results show that stalling cells in the G1/S boundary can increase prime editing efficiency, and plasmid editing enriches for genomic editing. The findings demonstrate that fluoPEER can be used for rapid and efficient correction of patient cells, selection of gene-edited cells, and elucidation of cellular mechanisms needed for successful prime editing.
NATURE COMMUNICATIONS
(2022)
Article
Cell Biology
Md Mahfuz Al Mamun, Ihtisham Bukhari
Summary: The CRISPR/Cas9 system has greatly revolutionized genome-editing technology, but existing methods are often laborious and inefficient. This study presents an efficient, inexpensive, and rapid one-step protocol for CRISPR/Cas9-assisted gene knockout.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2022)
Editorial Material
Cell & Tissue Engineering
Daniel E. Bauer
Summary: In this study, Ferrari et al. identified issues with commonly used AAV donors in gene editing, including weakened hematopoietic repopulation and frequent genomic integrations.
Article
Biochemistry & Molecular Biology
Omer Habib, Gizem Habib, Gue-Ho Hwang, Sangsu Bae
Summary: Prime editing is a precise and versatile genome editing technique that can directly copy desired genetic modifications into target DNA sites. It has great potential for gene function analysis, disease modeling, and correction of pathogenic mutations. In this study, prime editing was successfully tested in human pluripotent stem cells (hPSCs) and compared with base editing. Whole-genome sequencing showed that prime editing does not lead to guide RNA-independent off-target mutations in the genome.
NUCLEIC ACIDS RESEARCH
(2022)
Review
Pharmacology & Pharmacy
Masataka Nishiga, Lei S. Qi, Joseph C. Wu
Summary: Advancements in genome editing technology, particularly the CRISPR/Cas9 system, have revolutionized biomedical research and hold great promise for therapeutic applications in treating diseases, including those in the cardiovascular field. Therapeutic genome editing strategies are already being tested in clinical trials for hematopoietic diseases and show potential for treating a wide range of conditions.
ADVANCED DRUG DELIVERY REVIEWS
(2021)
Review
Cell Biology
Lola Koniali, Carsten W. Lederer, Marina Kleanthous
Summary: Advances in HSC genome editing as a treatment for inherited disorders have shown significant progress, with their versatility and accuracy driving potential therapeutic approaches for diseases. The focus of research is on improving the efficiency of HSC modification, treatment tolerability, and the distribution and affordability of corresponding therapies.
Article
Biochemical Research Methods
Stefan J. Tekel, Nicholas Brookhouser, Kylie Standage-Beier, Xiao Wang, David A. Brafman
Summary: The introduction of transient reporters of editing enrichment (TREE) has enabled highly efficient single-base editing of human cells using a transient episomal fluorescent reporter, allowing for rapid generation of clonal editing efficiencies exceeding 80% in biallelic or multiplexed edited isogenic human pluripotent stem cell lines within approximately 3-4 weeks.
Article
Medicine, Research & Experimental
Aryaman Girish Patwardhan, Sateesh Belemkar
Summary: Alzheimer's disease is a chronic illness with pathological hallmarks of amyloid plaques and neurofibrillary tangles, genetic predisposition, and current treatments being mainly palliative. New therapeutic approaches like stem cell therapy and gene editing are seen as promising directions for the future.
Article
Cell & Tissue Engineering
Kuo-Hsuan Chang, Cheng-Yen Huang, Chih-Hsin Ou-Yang, Chang-Han Ho, Han-Yi Lin, Chia-Lang Hsu, You-Tzung Chen, Yu-Chi Chou, Yi-Jing Chen, Ying Chen, Jia-Li Lin, Ji-Kuan Wang, Pei-Wen Lin, Ying-Ru Lin, Miao-Hsia Lin, Chi-Kang Tseng, Chin-Hsien Lin
Summary: This study compared the mutation correction efficiency and off-target effects between HDR and ABEs in iPSCs carrying the LRRK2 c.G6055A (p.G2019S) mutation. Results showed that ABE had a higher correction rate (24.5%) but no off-target effects, while HDR had a higher deletion rate (57.4%) but no ABE clones. The corrected iPSC-derived dopaminergic neurons exhibited reduced LRRK2 kinase activity, decreased phospho-alpha-synuclein expression, and mitigated neurite shrinkage and apoptosis. Transciptomic and proteomic analysis identified differences in gene expression related to energy metabolism, protein degradation, and peroxisome proliferator-activated receptor pathways between mutant and isogenic control cells.
STEM CELL RESEARCH & THERAPY
(2021)
Review
Biochemistry & Molecular Biology
Zhenwu Zhang, Xinyu Bao, Chao-Po Lin
Summary: The use of programmable nucleases in gene editing has had a significant impact on basic biology and clinical translation. Gene editing in human pluripotent stem cells (PSCs) is relevant to clinical cell therapy and requires cautious examination due to the potential for off-target edits and DNA damage. New gene editing tools, such as base editors and prime editors, offer a way to avoid these consequences. Additionally, advancements in understanding the microbial world have expanded the toolbox for gene editing.
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
Cell & Tissue Engineering
Miodrag Stojkovic, Dongjun Han, Minjin Jeong, Petra Stojkovic, Konstantina M. Stankovic
Summary: The development of human induced pluripotent stem cells (hiPSCs) and genome editing (GE) technologies provide new opportunities to understand the pathogenesis of sensorineural hearing loss (SNHL) in humans and identify new therapeutic approaches. However, important challenges associated with hiPSCs and GE need to be addressed before translating research findings into effective and safe clinical applications.
Review
Biochemistry & Molecular Biology
Behrouz Mollashahi, Hamid Latifi-Navid, Iman Owliaee, Sara Shamdani, Georges Uzan, Saleh Jamehdor, Sina Naserian
Summary: CRISPR is the most widely used genome editing toolkit that allows for the replacement and modification of DNA and RNA nucleotides. It has been used by researchers to investigate the function of stem cell genes and various gene editing techniques such as knock-out, knock-in, gene activation, and inhibition. This review article discusses recent developments and applications of CRISPR in stem cell research and clinical purposes, as well as different delivery methods and off-target detecting strategies.
Review
Biochemistry & Molecular Biology
Chenyu Lu, Jingyu Kuang, Tong Shao, Sisi Xie, Ming Li, Lingyun Zhu, Lvyun Zhu
Summary: Prime editing technology has shown attractive potential for versatile genome editing ability, but improvements are needed in terms of editing efficiency, off-target effects, and delivery systems. Recent optimizations have resulted in promising prospects for its application in various fields. This review provides a concise insight into the development, barriers, optimization efforts, and application directions of prime editing, offering clues for future advancements in this emerging field.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Multidisciplinary Sciences
So Hyun Park, Mingming Cao, Yidan Pan, Timothy H. Davis, Lavanya Saxena, Harshavardhan Deshmukh, Yilei Fu, Todd Treangen, Vivien A. Sheehan, Gang Bao
Summary: CRISPR-Cas9 genome editing can induce large gene modifications, such as deletions, insertions, and complex rearrangements. The study found that large deletions occur with high frequencies in hematopoietic stem and progenitor cells, which has important implications for genome editing technologies in treating human diseases.
Article
Surgery
Michael Y. Shino, Qiuheng Zhang, Ning Li, Ariss Derhovanessian, Allison Ramsey, Rajan Saggar, Ian N. Britton, Olawale O. Amubieya, Shahrzad M. Lari, Michelle Hickey, Elaine F. Reed, Paul W. Noble, Barry R. Stripp, Gregory A. Fishbein, Joseph P. Lynch, Abbas Ardehali, David M. Sayah, S. Sam Weigt, John A. Belperio
Summary: This study found that after lung transplantation, the presence of donor-specific HLA antibodies (DSAs) was associated with an increased risk of CLAD development, while non-donor specific anti-HLA antibodies (non-DSAs) generally did not increase CLAD risk but could do so when combined with high BAL CXCL9 levels. The study also highlighted the potential utility of BAL CXCL9 measurement as a biomarker for risk stratifying HLA antibodies in future CLAD management.
AMERICAN JOURNAL OF TRANSPLANTATION
(2022)
Article
Immunology
S. Samuel Weigt, Grace-Hyun J. Kim, Heather D. Jones, Allison L. Ramsey, Olawale Amubieya, Fereidoun Abtin, Lila Pourzand, Jihey Lee, Michael Y. Shino, Ariss DerHovanessian, Barry Stripp, Paul W. Noble, David M. Sayah, Rajan Saggar, Ian Britton, Joseph P. Lynch, John A. Belperio, Jonathan Goldin
Summary: This study demonstrates the potential of using quantitative image analysis (QIA) on chest high-resolution computed tomography (HRCT) to determine radiographic phenotypes in chronic lung allograft dysfunction (CLAD) at onset. The study found that different phenotypes had varying proportions of interstitial disease and air-trapping, which were also associated with survival outcomes.
Article
Respiratory System
Konstantinos Evangelou, Dimitris Veroutis, Koralia Paschalaki, Periklis G. Foukas, Nefeli Lagopati, Marios Dimitriou, Angelos Papaspyropoulos, Bindu Konda, Orsalia Hazapis, Aikaterini Polyzou, Sophia Havaki, Athanassios Kotsinas, Christos Kittas, Athanasios G. Tzioufas, Laurence De Leval, Demetris Vassilakos, Sotirios Tsiodras, Barry R. Stripp, Argyris Papantonis, Giovanni Blandino, Ioannis Karakasiliotis, Peter J. Barnes, Vassilis G. Gorgoulis
Summary: This study found that SARS-CoV-2 infection in severe COVID-19 patients leads to cellular senescence and a proinflammatory phenotype in AT2 cells. In vitro experiments showed that SARS-CoV-2 infection induces cell senescence and inflammation. Infected senescent cells may contribute to SARS-CoV-2 mutagenesis mediated by APOBEC enzymes.
EUROPEAN RESPIRATORY JOURNAL
(2022)
Review
Cell & Tissue Engineering
Ting Xie, Heather Lynn, William C. Parks, Barry Stripp, Peter Chen, Dianhua Jiang, Paul W. Noble
Summary: Recent advances in single-cell RNA sequencing and epithelium lineage labeling have identified multiple abnormal epithelial progenitor populations during lung regeneration after fibrotic injury. These abnormal cells, including basaloid/basal-like cells, ATII transition cells, and persistent epithelial progenitors (PEPs), accumulate in response to both chronic and acute pulmonary injury. Among these progenitors, PEPs express a distinct Krt8(+) phenotype rarely found in intact alveoli. Understanding the characteristics and functions of these abnormal epithelial progenitors and the signaling pathways regulating their phenotype could lead to new therapeutic targets for fibrosing lung diseases.
STEM CELL RESEARCH & THERAPY
(2022)
Article
Immunology
Gantsetseg Tumurkhuu, Duygu Ercan Laguna, Richard E. Moore, Jorge Contreras, Gabriela De Los Santos, Luisa Akaveka, Erica N. Montano, Yizhou Wang, Mariko Ishimori, Swamy Venuturupalli, Lindsy J. Forbess, Barry R. Stripp, Daniel J. Wallace, Caroline A. Jefferies
Summary: Diffuse alveolar hemorrhage (DAH) is a rare but life-threatening complication of systemic lupus erythematosus (SLE). Studies suggest that neutrophils and NETs play a significant role in inducing ER stress response and lung hemorrhage in the Pristane-induced model.
FRONTIERS IN IMMUNOLOGY
(2022)
Review
Oncology
Gianni Carraro, Barry R. Stripp
Summary: This article summarizes recent advances in understanding disease-related changes in the molecular phenotype of human lung epithelium, focusing on emerging concepts of epithelial transitional states that characterize pathological remodeling in chronic lung diseases. Single-cell transcriptomic studies have revealed cellular changes in epithelial cells associated with diseases such as idiopathic pulmonary fibrosis, chronic obstructive pulmonary disease, cystic fibrosis, and asthma. These studies provide new insights and contribute to our understanding of disease mechanisms.
JOURNAL OF PATHOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Bindu Konda, Apoorva Mulay, Changfu Yao, Edo Israely, Stephen Beil, Carissa A. Huynh, Warren G. Tourtellotte, Reinaldo Rampolla, Peter Chen, Gianni Carraro, Barry R. Stripp
Summary: This study describes a method for cryobanking of epithelial cells from mouse or human lung tissue to preserve their phenotypic and functional characteristics. Comparison analysis showed that cryobanked lung tissue cells were comparable to freshly dissociated cells in both phenotype and function. This method is important for creating an easily accessible tissue resource for the research community and downstream analysis of lung cell function and molecular phenotype.
AMERICAN JOURNAL OF RESPIRATORY CELL AND MOLECULAR BIOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Guanling Huang, Jiurong Liang, Kevin Huang, Xue Liu, Forough Taghavifar, Changfu Yao, Tanyalak Parimon, Ningshan Liu, Kristy Dai, Adam Aziz, Yizhou Wang, Richard T. Waldron, Hongmei Mou, Barry Stripp, Paul W. Noble, Dianhua Jiang
Summary: Loss of epithelial integrity, bronchiolarization, and fibroblast activation are key characteristics of idiopathic pulmonary fibrosis (IPF). Basal cells and basal cell-derived WNT7A play important roles in the fibrotic niche, promoting fibrogenesis and inhibiting AEC2 renewal. Targeting WNT7A may provide a novel strategy for IPF treatment.
AMERICAN JOURNAL OF RESPIRATORY CELL AND MOLECULAR BIOLOGY
(2023)
Article
Medicine, Research & Experimental
Konstantinos-Dionysios Alysandratos, Carolina Garcia-de-Alba, Changfu Yao, Patrizia Pessina, Jessie Huang, Carlos Villacorta-Martin, Olivia T. Hix, Kasey Minakin, Claire L. Burgess, Pushpinder Bawa, Aditi Murthy, Bindu Konda, Michael F. Beers, Barry R. Stripp, Carla F. Kim, Darrell N. Kotton
Summary: This study compared the transcriptomes of primary adult human AEC2s, their cultured progeny, and human induced pluripotent stem cell-derived AEC2s, and found that each population has a distinct transcriptomic space, with cultured AEC2s showing similarities and differences from freshly purified cells. The study also discovered an inverse relationship between proliferative and maturation states across each cell type. Additionally, it was found that cultures of both types of human AEC2s did not generate alveolar type 1 cells, but a subset of induced pluripotent stem cell-derived AEC2s acquired a transitional cell state when co-cultured with fibroblasts.
Letter
Critical Care Medicine
Changfu Yao, Tanyalak Parimon, Milena S. Espindola, Miriam S. Hohmann, Bindu Konda, Cory M. Hogaboam, Barry R. Stripp, Peter Chen
AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE
(2023)
Letter
Critical Care Medicine
Ruobing Wang, Chantelle Simone-Roach, Jonathan Lindstrom-Vautrin, Feiya Wang, Stuart Rollins, Pushpinder Singh Bawa, Junjie Lu, Yang Tang, Mary Lou Beermann, Thorsten Schlaeger, John Mahoney, Steven M. Rowe, Finn J. Hawkins, Darrell N. Kotton
AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE
(2023)
Article
Biology
Jiurong Liang, Guanling Huang, Xue Liu, Ningshan Liu, Forough Taghavifar, Kristy Dai, Changfu Yao, Nan Deng, Yizhou Wang, Peter Chen, Cory Hogaboam, Barry R. Stripp, William C. Parks, Paul W. Noble, Dianhua Jiang
Summary: This study systematically examined the genomic program changes of type 2 alveolar epithelial cells (AEC2s) in aging and after lung injury, and identified the synergistic effects of aging and AEC2 injury in promoting fibrosis. The study provides new insights into the interactions between aging and lung injury, and their impact on AEC2 cells in the diseased idiopathic pulmonary fibrosis (IPF).
Article
Respiratory System
Divya A. Shankar, Allan J. Walkey, Finn J. Hawkins, Nicholas A. Bosch, Daniel Peterson, Anica C. Law
Summary: This study examined the variation in practices and mortality for patients with severe idiopathic pulmonary fibrosis (IPF) exacerbations across different hospitals. The results showed significant differences in the use of invasive and non-invasive mechanical ventilation and corticosteroids, while the use of immunosuppressants and/or antioxidants showed less variation. Further research is needed to understand the effectiveness of different treatment strategies.
BMJ OPEN RESPIRATORY RESEARCH
(2023)
Review
Cell Biology
Tanyalak Parimon, Peter Chen, Barry R. Stripp, Jiurong Liang, Dianhua Jiang, Paul W. Noble, William C. Parks, Changfu Yao
Summary: Pulmonary fibrosis refers to a group of chronic lung diseases that impose a significant burden on patients and public health. Idiopathic pulmonary fibrosis (IPF) is the most common and severe form of these diseases and is mainly treated by lung transplantation. Research has shown that repeated injury and cellular senescence of alveolar epithelial cells contribute to the development and progression of fibrosis.
AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY
(2023)
Meeting Abstract
Critical Care Medicine
Z. Ortega, L. Xiao, C. Soto, E. Baghramian, S. Kabir, M. Zuttion, B. Victor, C. Yao, K. Colin, C. M. Hogaboam, P. W. Noble, B. R. Stripp, S. A. Gharib, P. Chen, T. Parimon
AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE
(2023)