keyword
https://read.qxmd.com/read/38497929/therapeutic-targeting-at-genome-mutations-of-liver-cancer-by-the-insertion-of-hsv1-thymidine-kinase-through-cas9-mediated-editing
#1
JOURNAL ARTICLE
Muhamuda Kader, Wei Sun, Bao-Guo Ren, Yan-Ping Yu, Junyan Tao, Lesley M Foley, Silvia Liu, Satdarshan P Monga, Jian-Hua Luo
BACKGROUND: Liver cancer is one of the most lethal malignancies for humans. The treatment options for advanced-stage liver cancer remain limited. A new treatment is urgently needed to reduce the mortality of the disease. METHODS: In this report, we developed a technology for mutation site insertion of a suicide gene (herpes simplex virus type 1- thymidine kinase) based on type II CRISPR RNA-guided endonuclease Cas9-mediated genome editing to treat liver cancers...
April 1, 2024: Hepatology Communications
https://read.qxmd.com/read/38497097/genomics-research-of-lifetime-depression-in-the-netherlands-the-biobanks-netherlands-internet-collaboration-bionic-project
#2
JOURNAL ARTICLE
Floris Huider, Yuri Milaneschi, Jouke-Jan Hottenga, Mariska Bot, M Liset Rietman, Almar A L Kok, Tessel E Galesloot, Leen M 't Hart, Femke Rutters, Marieke T Blom, Didi Rhebergen, Marjolein Visser, Ingeborg Brouwer, Edith Feskens, Catharina A Hartman, Albertine J Oldehinkel, Eco J C de Geus, Lambertus A Kiemeney, Martijn Huisman, H Susan J Picavet, W M Monique Verschuren, Hanna M van Loo, Brenda W J H Penninx, Dorret I Boomsma
In this cohort profile article we describe the lifetime major depressive disorder (MDD) database that has been established as part of the BIObanks Netherlands Internet Collaboration (BIONIC). Across the Netherlands we collected data on Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition ( DSM-5 ) lifetime MDD diagnosis in 132,850 Dutch individuals. Currently, N = 66,684 of these also have genomewide single nucleotide polymorphism (SNP) data. We initiated this project because the complex genetic basis of MDD requires large population-wide studies with uniform in-depth phenotyping...
March 18, 2024: Twin Research and Human Genetics: the Official Journal of the International Society for Twin Studies
https://read.qxmd.com/read/38496583/activation-of-the-imprinted-prader-willi-syndrome-locus-by-crispr-based-epigenome-editing
#3
Dahlia Rohm, Joshua B Black, Sean R McCutcheon, Alejandro Barrera, Daniel J Morone, Xander Nuttle, Celine E de Esch, Derek J C Tai, Michael E Talkowski, Nahid Iglesias, Charles A Gersbach
Epigenome editing with DNA-targeting technologies such as CRISPR-dCas9 can be used to dissect gene regulatory mechanisms and potentially treat associated disorders. For example, Prader-Willi Syndrome (PWS) is caused by loss of paternally expressed imprinted genes on chromosome 15q11.2-q13.3, although the maternal allele is intact but epigenetically silenced. Using CRISPR repression and activation screens in human induced pluripotent stem cells (iPSCs), we identified genomic elements that control expression of the PWS gene SNRPN from the paternal and maternal chromosomes...
March 4, 2024: bioRxiv
https://read.qxmd.com/read/38496503/precision-enhancement-of-car-nk-cells-through-non-viral-engineering-and-highly-multiplexed-base-editing
#4
Minjing Wang, Joshua B Krueger, Alexandria K Gilkey, Erin M Stelljes, Mitchell G Kluesner, Emily J Pomeroy, Joseph G Skeate, Nicholas J Slipek, Walker S Lahr, Patricia N Claudio Vázquez, Yueting Zhao, Ella J Eaton, Kanut Laoharawee, Beau R Webber, Branden S Moriarity
Natural killer (NK) cells' unique ability to kill transformed cells expressing stress ligands or lacking major histocompatibility complexes (MHC) has prompted their development for immunotherapy. However, NK cells have demonstrated only moderate responses against cancer in clinical trials and likely require advanced genome engineering to reach their full potential as a cancer therapeutic. Multiplex genome editing with CRISPR/Cas9 base editors (BE) has been used to enhance T cell function and has already entered clinical trials but has not been reported in human NK cells...
March 8, 2024: bioRxiv
https://read.qxmd.com/read/38496463/modeling-the-genomic-complexity-of-human-cancer-using-cas12a-mice
#5
Jess D Hebert, Haiqing Xu, Yuning J Tang, Paloma A Ruiz, Colin Detrick, Jing Wang, Nicholas W Hughes, Oscar Donosa, Laura Andrejka, Saswati Karmakar, Irenosen Aboiralor, Le Cong, Julien Sage, Dmitri A Petrov, Monte M Winslow
Somatic genome editing in mouse models has increased our understanding of the in vivo effects of genetic alterations in areas ranging from neuroscience to cancer biology and beyond. However, existing models have been restricted in their ability to create multiple targeted edits, which has limited investigations into complex genetic interactions that underlie development, homeostasis, and disease. To accelerate and expand the generation of complex genotypes in somatic cells, we generated transgenic mice with Cre-regulated and constitutive expression of enhanced Acidaminococcus sp...
March 8, 2024: bioRxiv
https://read.qxmd.com/read/38494539/crop-bioengineering-via-gene-editing-reshaping-the-future-of-agriculture
#6
REVIEW
Mohamed Atia, Wenjun Jiang, Khalid Sedeek, Haroon Butt, Magdy Mahfouz
Genome-editing technologies have revolutionized research in plant biology, with major implications for agriculture and worldwide food security, particularly in the face of challenges such as climate change and increasing human populations. Among these technologies, clustered regularly interspaced short palindromic repeats [CRISPR]-CRISPR-associated protein [Cas] systems are now widely used for editing crop plant genomes. In this review, we provide an overview of CRISPR-Cas technology and its most significant applications for improving crop sustainability...
March 18, 2024: Plant Cell Reports
https://read.qxmd.com/read/38494000/the-unique-biodegradation-pathway-of-benzo-a-pyrene-in-moderately-halophilic-pontibacillus-chungwhensis-hn14
#7
JOURNAL ARTICLE
Zhihui Qian, Haichen Yang, Jin Li, Tao Peng, Tongwang Huang, Zhong Hu
Benzo[a]pyrene (BaP), as the typical representative of polycyclic aromatic hydrocarbons (PAHs), is a serious hazard to human health and natural environments. Though the study of microbial degradation of PAHs has persisted for decades, the degradation pathway of BaP is still unclear. Previously, Pontibacillus chungwhensis HN14 was isolated from high salinity environment exhibiting a high BaP degradation ability. Here, based on the intermediates identified, BaP was found to be transformed to 4,5-epoxide-BaP, BaP-trans-4,5-dihydrodiol, 1,2-dihydroxy-phenanthrene, 2-carboxy-1-naphthol, and 4,5-dimethoxybenzo[a]pyrene by the strain HN14...
March 15, 2024: Chemosphere
https://read.qxmd.com/read/38493444/integrative-regulation-of-hlmr1-by-dietary-and-genetic-factors-in-nonalcoholic-fatty-liver-disease-and-hyperlipidemia
#8
JOURNAL ARTICLE
Marcos E Jaso-Vera, Shohei Takaoka, Ishika Patel, Xiangbo Ruan
Long non-coding RNA (lncRNA) genes represent a large class of transcripts that are widely expressed across species. As most human lncRNAs are non-conserved, we recently employed a unique humanized liver mouse model to study lncRNAs expressed in human livers. We identified a human hepatocyte-specific lncRNA, hLMR1 (human lncRNA metabolic regulator 1), which is induced by feeding and promotes hepatic cholesterol synthesis. Recent genome-wide association studies (GWAS) found that several single-nucleotide polymorphisms (SNPs) from the hLMR1 gene locus are associated with blood lipids and markers of liver damage...
March 17, 2024: Human Genetics
https://read.qxmd.com/read/38489357/precise-large-fragment-deletions-in-mammalian-cells-and-mice-generated-by-dcas9-controlled-crispr-cas3
#9
JOURNAL ARTICLE
Jinze Li, Ding Zhao, Tao Zhang, Haoyang Xiong, Mingyang Hu, Hongmei Liu, Feiyu Zhao, Xiaodi Sun, Peng Fan, Yuqiang Qian, Di Wang, Liangxue Lai, Tingting Sui, Zhanjun Li
Currently, the Cas9 and Cas12a systems are widely used for genome editing, but their ability to precisely generate large chromosome fragment deletions is limited. Type I-E CRISPR mediates broad and unidirectional DNA degradation, but controlling the size of Cas3-mediated DNA deletions has proven elusive thus far. Here, we demonstrate that the endonuclease deactivation of Cas9 (dCas9) can precisely control Cas3-mediated large-fragment deletions in mammalian cells. In addition, we report the elimination of the Y chromosome and precise retention of the Sry gene in mice using CRISPR/Cas3 and dCas9-controlled CRISPR/Cas3, respectively...
March 15, 2024: Science Advances
https://read.qxmd.com/read/38487002/genome-editing-of-par2-through-targeted-delivery-of-crispr-cas9-system-for-alleviating-acute-lung-inflammation-via-erk-nlrp3-il-1-%C3%AE-and-no-inos-signalling
#10
JOURNAL ARTICLE
Xin Zhuo, Yue Wu, Xiujuan Fu, Jianbin Li, Yuxin Xiang, Xiaoyu Liang, Canquan Mao, Yuhong Jiang
Excessive and uncontrollable inflammatory responses in alveoli can dramatically exacerbate pulmonary disease progressions through vigorous cytokine releases, immune cell infiltration and protease-driven tissue damages. It is an urgent need to explore potential drug strategies for mitigating lung inflammation. Protease-activated receptor 2 (PAR2) as a vital molecular target principally participates in various inflammatory diseases via intracellular signal transduction. However, it has been rarely reported about the role of PAR2 in lung inflammation...
March 2024: Acta Pharmaceutica Sinica. B
https://read.qxmd.com/read/38483978/engineering-of-cas12a-nuclease-variants-with-enhanced-genome-editing-specificity
#11
JOURNAL ARTICLE
Peng Chen, Jin Zhou, Huan Liu, Erchi Zhou, Boxiao He, Yankang Wu, Hongjian Wang, Zaiqiao Sun, Chonil Paek, Jun Lei, Yongshun Chen, Xinghua Zhang, Lei Yin
The clustered regularly interspaced short palindromic repeat (CRISPR)-Cas12a system is a powerful tool in gene editing; however, crRNA-DNA mismatches might induce unwanted cleavage events, especially at the distal end of the PAM. To minimize this limitation, we engineered a hyper fidelity AsCas12a variant carrying the mutations S186A/R301A/T315A/Q1014A/K414A (termed HyperFi-As) by modifying amino acid residues interacting with the target DNA and crRNA strand. HyperFi-As retains on-target activities comparable to wild-type AsCas12a (AsCas12aWT) in human cells...
March 14, 2024: PLoS Biology
https://read.qxmd.com/read/38474336/zebrafish-ccnf-and-fus-mediate-stress-specific-motor-responses
#12
JOURNAL ARTICLE
Yagiz Alp Aksoy, Alexander J Cole, Wei Deng, Daniel Hesselson
Amyotrophic lateral sclerosis (ALS) is a devastating neurodegenerative disease characterized by the degeneration of motor neurons. Mutations in the cyclin F ( CCNF ) and fused in sarcoma ( FUS ) genes have been associated with ALS pathology. In this study, we aimed to investigate the functional role of CCNF and FUS in ALS by using genome editing techniques to generate zebrafish models with genetic disruptions in these genes. Sequence comparisons showed significant homology between human and zebrafish CCNF and FUS proteins...
February 21, 2024: Cells
https://read.qxmd.com/read/38474188/defective-biomechanics-and-pharmacological-rescue-of-human-cardiomyocytes-with-filamin-c-truncations
#13
JOURNAL ARTICLE
Marco Lazzarino, Michele Zanetti, Suet Nee Chen, Shanshan Gao, Brisa Peña, Chi Keung Lam, Joseph C Wu, Matthew R G Taylor, Luisa Mestroni, Orfeo Sbaizero
Actin-binding filamin C (FLNC) is expressed in cardiomyocytes, where it localizes to Z-discs, sarcolemma, and intercalated discs. Although FLNC truncation variants ( FLNCtv ) are an established cause of arrhythmias and heart failure, changes in biomechanical properties of cardiomyocytes are mostly unknown. Thus, we investigated the mechanical properties of human-induced pluripotent stem cells-derived cardiomyocytes (hiPSC-CMs) carrying FLNCtv . CRISPR/Cas9 genome-edited homozygous FLNCKO-/- hiPSC-CMs and heterozygous knock-out FLNCKO+/- hiPSC-CMs were analyzed and compared to wild-type FLNC (FLNCWT ) hiPSC-CMs...
March 3, 2024: International Journal of Molecular Sciences
https://read.qxmd.com/read/38473704/current-strategies-for-increasing-knock-in-efficiency-in-crispr-cas9-based-approaches
#14
REVIEW
Andrés Felipe Leal, Angelica María Herreno-Pachón, Eliana Benincore-Flórez, Amali Karunathilaka, Shunji Tomatsu
Since its discovery in 2012, the clustered regularly interspaced short palindromic repeats (CRISPR) and CRISPR-associated protein 9 (Cas9) system has supposed a promising panorama for developing novel and highly precise genome editing-based gene therapy (GT) alternatives, leading to overcoming the challenges associated with classical GT. Classical GT aims to deliver transgenes to the cells via their random integration in the genome or episomal persistence into the nucleus through lentivirus (LV) or adeno-associated virus (AAV), respectively...
February 20, 2024: International Journal of Molecular Sciences
https://read.qxmd.com/read/38473423/transcriptomic-proteomic-and-genomic-mutational-fraction-differences-based-on-hpv-status-observed-in-patient-derived-xenograft-models-of-penile-squamous-cell-carcinoma
#15
JOURNAL ARTICLE
Niki M Zacharias, Luis Segarra, Keiko Akagi, Natalie Wall Fowlkes, Huiqin Chen, Angelita Alaniz, Carolyn de la Cerda, Pedro Pesquera, Yuanxin Xi, Jing Wang, Jad Chahoud, Xin Lu, Priya Rao, Magaly Martinez-Ferrer, Curtis A Pettaway
Metastatic penile squamous cell carcinoma (PSCC) has only a 50% response rate to first-line combination chemotherapies and there are currently no targeted-therapy approaches. Therefore, we have an urgent need in advanced-PSCC treatment to find novel therapies. Approximately half of all PSCC cases are positive for high-risk human papillomavirus (HR-HPV). Our objective was to generate HPV-positive (HPV+) and HPV-negative (HPV-) patient-derived xenograft (PDX) models and to determine the biological differences between HPV+ and HPV- disease...
March 6, 2024: Cancers
https://read.qxmd.com/read/38472686/the-rre-rev-module-has-no-effect-on-the-packaging-efficiency-of-cas9-and-gag-proteins-into-nanomedic-virus-like-particles
#16
JOURNAL ARTICLE
N A Kruglova, D S Komkov, D V Mazurov, M V Shepelev
Delivery of ribonucleoprotein complexes of Cas9 nuclease and guide RNA into target cells with virus-like particles (VLP) is one of the novel methods of genome editing and is suitable for gene therapy of human diseases in the future. The efficiency of genome editing with VLPs depends on the Cas9 packaging into VLPs, the process mediated by the viral Gag protein. To improve the packaging of Cas9 into NanoMEDIC VLPs, plasmid constructs for Cas9 and Gag expression were modified by adding the HIV Rev response element (RRE), which was expected to increase the nuclear export of RRE-containing transcripts into the cytosol via the Rev accessory protein, as described for a Vpr-Cas9-based VLP system...
March 12, 2024: Doklady Biological Sciences: Proceedings of the Academy of Sciences of the USSR, Biological Sciences Sections
https://read.qxmd.com/read/38472198/identifying-regulators-of-aberrant-stem-cell-and-differentiation-activity-in-colorectal-cancer-using-a-dual-endogenous-reporter-system
#17
JOURNAL ARTICLE
Sandor Spisak, David Chen, Pornlada Likasitwatanakul, Paul Doan, Zhixin Li, Pratyusha Bala, Laura Vizkeleti, Viktoria Tisza, Pushpamali De Silva, Marios Giannakis, Brian Wolpin, Jun Qi, Nilay S Sethi
Aberrant stem cell-like activity and impaired differentiation are central to the development of colorectal cancer (CRC). To identify functional mediators of these key cellular programs, we engineer a dual endogenous reporter system by genome-editing the SOX9 and KRT20 loci of human CRC cell lines to express fluorescent reporters, broadcasting aberrant stem cell-like and differentiation activity, respectively. By applying a CRISPR screen targeting 78 epigenetic regulators with 542 sgRNAs to this platform, we identify factors that contribute to stem cell-like activity and differentiation in CRC...
March 12, 2024: Nature Communications
https://read.qxmd.com/read/38471738/rna-pol-ii-dependent-transcription-efficiency-fine-tunes-a-to-i-editing-levels
#18
JOURNAL ARTICLE
Brigitta Szabo, Therese C Mandl, Bernhard Woldrich, Gregor Diensthuber, David Martin, Michael F Jantsch, Konstantin Licht
A-to-I RNA editing is a widespread epitranscriptomic phenomenon leading to the conversion of adenosines to inosines, which are primarily interpreted as guanosines by cellular machines. Consequently, A-to-I editing can alter splicing or lead to recoding of transcripts. As misregulation of editing can cause a variety of human diseases, A-to-I editing requires tight regulation of the extent of deamination, particularly in protein-coding regions. The bulk of A-to-I editing occurs cotranscriptionally. Thus, we studied A-to-I editing regulation in the context of transcription and pre-mRNA processing...
March 12, 2024: Genome Research
https://read.qxmd.com/read/38471390/comparison-of-icsi-ivf-and-in-vivo-derived-embryos-to-produce-crispr-cas9-gene-edited-pigs-for-xenotransplantation
#19
JOURNAL ARTICLE
Olinda Briski, Gastón Emilio La Motta, Laura Daniela Ratner, Federico Andrés Allegroni, Santiago Pillado, Guadalupe Álvarez, Betiana Gutierrez, Lisa Tarragona, Andrea Zaccagnini, Marcelo Acerbo, Carla Ciampi, Rafael Fernández-Martin, Daniel Felipe Salamone
Genome editing in pigs for xenotransplantation has seen significant advances in recent years. This study compared three methodologies to generate gene-edited embryos, including co-injection of sperm together with the CRISPR-Cas9 system into oocytes, named ICSI-MGE (mediated gene editing); microinjection of CRISPR-Cas9 components into oocytes followed by in vitro fertilization (IVF), and microinjection of in vivo fertilized zygotes with the CRISPR-Cas9 system. Our goal was to knock-out (KO) porcine genes involved in the biosynthesis of xenoantigens responsible for the hyperacute rejection of interspecific xenografts, namely GGTA1, CMAH, and β4GalNT2...
February 27, 2024: Theriogenology
https://read.qxmd.com/read/38468733/revolutionizing-agriculture-harnessing-crispr-cas9-for-crop-enhancement
#20
REVIEW
Ashish Chovatiya, Riddhi Rajyaguru, Rukam Singh Tomar, Preetam Joshi
Plant crops serve as essential sources of nutritional sustenance, supplying vital nutrients to human diets. However, their productivity and quality are severely jeopardized by factors such as pests, diseases, and adverse abiotic conditions. Addressing these challenges using innovative biotechnological approaches is imperative for advancing sustainable agriculture. In recent years, genome editing technologies have emerged as pivotal genetic tools, revolutionizing plant molecular biology. Among these, the CRISPR-Cas9 system has gained prominence due to its unparalleled precision, streamlined design, and heightened success rates...
March 2024: Indian Journal of Microbiology
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