Article
Immunology
Gerson Dierley Keppeke, Larissa Diogenes, Kethellen Gomes, Luis Eduardo Coelho Andrade
Summary: Autoantibodies (AAbs) are biomarkers with pathogenic roles. Standard therapies for eliminating specific B/plasma-cell clones are not fully efficient. CRISPR/Cas9 genome-editing effectively knocked out genes producing pathogenic AAbs in vitro, reducing antibody secretion and binding capacity. This approach has the potential to be a novel therapeutic approach for AAb-mediated diseases.
CLINICAL IMMUNOLOGY
(2023)
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
Parasitology
Monica Mendes Kangussu-Marcolino, Pedro Morgado, Dipak Manna, Heather Yee, Upinder Singh
Summary: The study optimized the use of CRISPR-Cas9 as a genetic tool in Entamoeba histolytica. The researchers demonstrated that Cas9 activity can facilitate homologous recombination in the parasite, suggesting the potential utility of this genome editing approach for genetic studies in early branching eukaryotes.
INTERNATIONAL JOURNAL FOR PARASITOLOGY
(2021)
Article
Multidisciplinary Sciences
Emmarie. C. C. Ryan, Leslie. M. M. Huggins, Joshua. D. D. Podlevsky
Summary: CRISPR arrays and Cas proteins are adaptive immune systems in bacteria and archaea, defending against genetic elements. The reprogrammable guide RNA of single effector CRISPR-Cas systems greatly facilitates gene-editing but complicates PCR tests. These systems are derived from human microflora and pathogens, making detection of gene-editor exposure difficult. To overcome false positives, a DNA displacement assay has been developed to specifically detect gene-editors without cross-reacting with bacterial CRISPRs.
SCIENTIFIC REPORTS
(2023)
Article
Biochemical Research Methods
Meliawati Meliawati, Christa Teckentrup, Jochen Schmid
Summary: The CRISPR-Cas system has been used for large cluster deletion and multiplex genome editing in Paenibacillus polymyxa. The study demonstrates that the Cas9-based system can achieve efficient targeted deletions and multiplex editing, which is expected to accelerate future research in P. polymyxa and related species.
ACS SYNTHETIC BIOLOGY
(2022)
Review
Biochemistry & Molecular Biology
Yulin Mu, Chengxiao Zhang, Taihua Li, Feng-Jie Jin, Yun-Ju Sung, Hee-Mock Oh, Hyung-Gwan Lee, Long Jin
Summary: Lactobacillus, important in food production and probiotics, can benefit from CRISPR/Cas9-based genome editing to improve strain efficiency and achieve traceless genome modification.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
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)
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)
Review
Agriculture, Dairy & Animal Science
Julia Popova, Victoria Bets, Elena Kozhevnikova
Summary: Genome editing has practical applications in farm animals, improving production traits, economic value, and disease resistance. It also has potential in biomedical research and drug production, as well as xenograft donors. Recent advancements in site-specific nucleases and embryological delivery methods have revolutionized transgenesis, providing efficient and reliable tools for genome engineering in agriculture.
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)
Review
Pharmacology & Pharmacy
Siwei Chen, Deng Chen, Bin Liu, Hidde J. Haisma
Summary: CRISPR/Cas9-mediated genome engineering has extensive applications in basic biology, biotechnology, and medicine. However, the low gene modification efficiency and uncontrollable prolonged Cas9 activity hinder its further use. Researchers have explored small molecules with clinical potential to precisely modulate CRISPR/Cas9 genome editing activity.
DRUG DISCOVERY TODAY
(2022)
Article
Biochemistry & Molecular Biology
Xiaoying Zhao, Kunli Qu, Benedetta Curci, Huanming Yang, Lars Bolund, Lin Lin, Yonglun Luo
Summary: Recent progress in CRISPR gene editing tools has expanded the possibilities for treating devastating genetic diseases. In this study, three methods of gene editing (NHBEJ, HDR, and PE) were compared for correcting loss-of-function mutations in Duchenne Muscular Dystrophy. The highest efficiency was achieved with NHBEJ, followed by HDR and PE2. The correction efficiency was increased with the use of PE3. This study demonstrates the potential for highly efficient correction of DMD mutations using CRISPR gene editing.
Article
Chemistry, Physical
Juhee Lee, Yoo Kyung Kang, Eonju Oh, Juhee Jeong, San Hae Im, Duk Ki Kim, Haeshin Lee, Sang-Gyu Kim, Keehoon Jung, Hyun Jung Chung
Summary: The study presents a cancer gene therapy strategy based on NanoRNP that efficiently blocks the PD-L1 immune checkpoint and induces an antitumor effect in vivo without the need for combination therapy. In vivo results demonstrate that NanoRNP can induce indels in target cells at high frequencies, significantly suppressing tumor growth.
CHEMISTRY OF MATERIALS
(2022)
Article
Multidisciplinary Sciences
Beate Rieblinger, Hicham Sid, Denise Duda, Tarik Bozoglu, Romina Klinger, Antonina Schlickenrieder, Kamila Lengyel, Krzysztof Flisikowski, Tatiana Flisikowska, Nina Simm, Alessandro Grodziecki, Carolin Perleberg, Andrea Bahr, Lucie Carrier, Mayuko Kurome, Valeri Zakhartchenko, Barbara Kessler, Eckhard Wolf, Lutz Kettler, Harald Luksch, Ibrahim T. Hagag, Daniel Wise, Jim Kaufman, Benedikt B. Kaufer, Christian Kupatt, Angelika Schnieke, Benjamin Schusser
Summary: Research on genetically modified animals has mostly focused on mice, but also includes species like pigs that are more physiologically similar to humans, and cross-species comparisons with phylogenetically distant species like chickens. CRISPR-Cas9 is a versatile genetic editing method applicable across various species. The successful generation of transgenic chickens and pigs that express Cas9 in all organs has confirmed the functionality of Cas9 across different target genes, cell types, and in vivo applications.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Article
Chemistry, Multidisciplinary
William Shu Ching Ngai, Shaojun Yang, Xiangmei Zeng, Yanjun Liu, Feng Lin, Xin Wang, Heng Zhang, Xinyuan Fan, Peng R. Chen
Summary: This article reports a bioorthogonally activatable base editor called BaseBAC, which can initiate pyroptosis in specific cells in situ and on demand. By establishing a bioorthogonal blockage on the PAM-interacting residue to control the enzymatic activity of a cytosine base editor, BaseBAC enables control over pyroptosis.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2022)
Article
Endocrinology & Metabolism
Maria J. Pereira, Johanna C. Andersson-Assarsson, Peter Jacobson, Prasad Kamble, Magdalena Taube, Kajsa Sjoholm, Lena M. S. Carlsson, Per-Arne Svensson
Summary: The study identified SLC19A3 as a novel adipose tissue-specific gene, with its expression regulated by body mass index and weight changes. This gene may play a key role in adipocyte metabolism.
OBESITY SCIENCE & PRACTICE
(2022)
Article
Endocrinology & Metabolism
Fozia Ahmed, Prasad G. Kamble, Susanne Hetty, Giovanni Fanni, Milica Vranic, Assel Sarsenbayeva, Robin Kristofi, Kristina Almby, Maria K. Svensson, Maria J. Pereira, Jan W. Eriksson
Summary: This study found that reduced estrogen levels in postmenopausal women can lead to metabolic side effects, particularly insulin resistance and type 2 diabetes. The results suggest that estrogen receptor expression in adipose tissue is lower in postmenopausal women, and E2 inhibits glucose utilization in human adipocytes. These findings may explain changes in glucose utilization after menopause and have implications for hormone treatment in postmenopausal women.
JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM
(2022)
Article
Medical Laboratory Technology
Bipasha Nandi Jui, Assel Sarsenbayeva, Henning Jernow, Susanne Hetty, Maria J. Pereira
Summary: This study compared traditional RNA extraction with a column-based method and found that the traditional method provides sufficient RNA yield and integrity, which is advantageous for small adipose tissue specimens. The column-based method showed lower RNA quantity and integrity, although the differences were not statistically significant. It also had lower levels of contaminants.
LABORATORY MEDICINE
(2022)
Article
Biotechnology & Applied Microbiology
Ludvig Bergenstrahle, Bryan He, Joseph Bergenstrahle, Xesus Abalo, Reza Mirzazadeh, Kim Thrane, Andrew L. Ji, Alma Andersson, Ludvig Larsson, Nathalie Stakenborg, Guy Boeckxstaens, Paul Khavari, James Zou, Joakim Lundeberg, Jonas Maaskola
Summary: This method improves the low resolution of spatial transcriptomics by integrating gene expression data with histological images, allowing for higher-resolution expression maps to be inferred. The deep generative model used in this method can predict spatial gene expression solely from histology images.
NATURE BIOTECHNOLOGY
(2022)
Article
Biophysics
Alejandra N. Torres, Ludgero Tavares, Maria J. Pereira, Jan W. Eriksson, John G. Jones
Summary: This study characterized the fatty acid composition and positional distribution of triglycerides in human subcutaneous adipose tissue using C-13 NMR spectroscopy. The study found that the sn2 position of triglycerides is enriched with monounsaturated fatty acids, while the sn1,3 position is enriched with saturated fatty acids. Furthermore, the study revealed a significant positive correlation between palmitoleic acid levels and both BMI and insulin sensitivity.
NMR IN BIOMEDICINE
(2023)
Article
Biochemistry & Molecular Biology
Maria J. Pereira, Ayesha Azim, Susanne Hetty, Bipasha Nandi Jui, Joel Kullberg, Martin H. Lundqvist, Jan W. Eriksson
Summary: This study aims to investigate the expression of interleukin-33 (IL-33) in subcutaneous adipose tissue (SAT) of type 2 diabetes (T2D) subjects and its effects on human adipocyte glucose uptake. The results showed that T2D subjects had higher IL-33 gene and protein expression in SAT, which was associated with insulin resistance and reduced gene expression of markers related to lipid storage and adipogenesis. Additionally, IL-33 treatment reduced adipocyte glucose uptake.
Article
Cell Biology
Milica Vranic, Fozia Ahmed, Susanne Hetty, Assel Sarsenbayeva, Vitor Ferreira, Giovanni Fanni, Angela M. Valverde, Jan W. Eriksson, Maria J. Pereira
Summary: We investigated the effects of second-generation antipsychotics (SGAs) on adipocyte differentiation and metabolism and found that aripiprazole (ARI) can impair adipocyte glucose uptake and increase fatty acid oxidation gene expression, while olanzapine (OLA) can increase leptin gene expression. These findings have important implications for understanding the metabolic effects of antipsychotic drugs and suggest that different SGAs may have different mechanisms of action.
MOLECULAR AND CELLULAR ENDOCRINOLOGY
(2023)
Article
Cell Biology
Alexandros Sountoulidis, Sergio Marco Salas, Emelie Braun, Christophe Avenel, Joseph Bergenstrahle, Jonas Theelke, Marco Vicari, Paulo Czarnewski, Andreas Liontos, Xesus Abalo, Zaneta Andrusivova, Reza Mirzazadeh, Michaela Asp, Xiaofei Li, Lijuan Hu, Sanem Sariyar, Anna Martinez Casals, Burcu Ayoglu, Alexandra Firsova, Jakob Michaelsson, Emma Lundberg, Carolina Waehlby, Erik Sundstroem, Sten Linnarsson, Joakim Lundeberg, Mats Nilsson, Christos Samakovlis
Summary: Sountoulidis et al. have created a spatial gene expression atlas of the human embryonic lung during the first trimester of gestation, identifying 83 cell states and developmental trajectories. They integrated single-cell RNA sequencing and spatially resolved transcriptomics, providing an open platform for interactive exploration. The atlas can serve as a reference for further research and understanding of pulmonary diseases.
NATURE CELL BIOLOGY
(2023)
Article
Multidisciplinary Sciences
David Lagman, Helen J. Haines, Xesus M. Abalo, Dan Larhammar
Summary: By analyzing gene sequences and chromosomal structures, this study discovered four previously unknown CNG subfamilies in metazoans and provided evidence that early vertebrate genome duplications played a crucial role in the evolution of the visual and central nervous systems.
Article
Multidisciplinary Sciences
Reza Mirzazadeh, Zaneta Andrusivova, Ludvig Larsson, Phillip T. Newton, Leire Alonso Galicia, Xesus M. Abalo, Mahtab Avijgan, Linda Kvastad, Alexandre Denadai-Souza, Nathalie Stakenborg, Alexandra B. Firsova, Alia Shamikh, Aleksandra Jurek, Niklas Schultz, Monica Nister, Christos Samakovlis, Guy Boeckxstaens, Joakim Lundeberg
Summary: Spatially resolved transcriptomics allows genome-wide mRNA expression profiling within tissue sections. The RNA quality is crucial for methods targeting mRNA polyA tails, and the high cost of current spatial transcriptomics assays requires careful sample screening. In this study, the authors introduce a workflow called RRST for mRNA recovery from fresh frozen specimens with moderate to low RNA quality, and demonstrate its robustness on different tissue types.
NATURE COMMUNICATIONS
(2023)
Article
Dermatology
Kim Thrane, Marten C. G. Winge, Hongyu Wang, Larry Chen, Margaret G. Guo, Alma Andersson, Xesus M. Abalo, Xue Yang, Daniel S. Kim, Sophia K. Longo, Brian Y. Soong, Jordan M. Meyers, David L. Reynolds, Aaron McGeever, Deniz Demircioglu, Dan Hasson, Reza Mirzazadeh, Adam J. Rubin, Gordon H. Bae, Jim Karkanias, Kerri Rieger, Joakim Lundeberg, Andrew L. Ji
Summary: This study integrates human and mouse skin data to explore the relationship between epidermal homeostasis, skin diseases, and cellular subpopulations, and identifies potential therapeutic targets.
JOURNAL OF INVESTIGATIVE DERMATOLOGY
(2023)
Article
Endocrinology & Metabolism
Martin H. Lundqvist, Maria J. Pereira, Kristina Almby, Susanne Hetty, Jan W. Eriksson
Summary: Counter-regulatory hormonal responses to glucose variations differ in individuals with type 2 diabetes, prediabetes, and normoglycemia, and may contribute to the progression of the disease by promoting insulin resistance and dysglycemia.
JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM
(2023)
Article
Endocrinology & Metabolism
Martin H. Lundqvist, Maria J. Pereira, Jan W. Eriksson
Summary: This study investigates whether inflammatory responses to glycemic and insulinemic variations are altered in obese individuals. The results show that hyperinsulinemia, hypoglycemia, and hyperglycemia lead to a decrease in multiple inflammatory markers, and the inflammatory response is more pronounced in obese individuals during hypoglycemia and hyperglycemia.
Article
Endocrinology & Metabolism
Fozia Ahmed, Milica Vranic, Susanne Hetty, Argyri Mathioudaki, Vagia Patsoukaki, Giovanni Fanni, Maria J. Pereira, Jan W. Eriksson
Summary: This study investigated the association of organic cation transporter 3 (OCT3) mRNA levels in subcutaneous adipose tissue with aging and markers of insulin resistance. The results showed that mRNA and protein levels of OCT3 increased with aging and were negatively associated with markers of insulin resistance. In addition, estradiol treatment resulted in a reduction in OCT3 mRNA levels.
Article
Endocrinology & Metabolism
Milica Vranic, Fozia Ahmed, Robin Kristofi, Susanne Hetty, Dariush Mokhtari, Maria K. Svensson, Jan W. Eriksson, Maria J. Pereira
Summary: This study evaluates the dopaminergic signaling in human adipose tissue in the context of obesity and type 2 diabetes (T2D) and its potential implications in adipose tissue metabolism. The results suggest that protein expression of DRD2 in subcutaneous adipose tissue is up-regulated with hyperglycemia and T2D, possibly as a compensatory mechanism. Additionally, dopamine receptor agonists inhibit adipocyte lipolysis and may have beneficial effects on lipid metabolism.