keyword
https://read.qxmd.com/read/38468291/the-construction-of-modular-universal-chimeric-antigen-receptor-t-mu-car-t-cells-by-covalent-linkage-of-allogeneic-t-cells-and-various-antibody-fragments
#21
JOURNAL ARTICLE
Tao Chen, Jieyi Deng, Yongli Zhang, Bingfeng Liu, Ruxin Liu, Yiqiang Zhu, Mo Zhou, Yingtong Lin, Baijin Xia, Keming Lin, Xiancai Ma, Hui Zhang
BACKGROUND: Chimeric antigen receptor-T (CAR-T) cells therapy is one of the novel immunotherapeutic approaches with significant clinical success. However, their applications are limited because of long preparation time, high cost, and interpersonal variations. Although the manufacture of universal CAR-T (U-CAR-T) cells have significantly improved, they are still not a stable and unified cell bank. METHODS: Here, we tried to further improve the convenience and flexibility of U-CAR-T cells by constructing novel modular universal CAR-T (MU-CAR-T) cells...
March 11, 2024: Molecular Cancer
https://read.qxmd.com/read/38457474/preclinical-toxicity-analyses-of-lentiviral-vectors-expressing-the-hiv-1-ltr-specific-designer-recombinase-brec1
#22
JOURNAL ARTICLE
Niklas Beschorner, Paul Künzle, Maike Voges, Ilona Hauber, Daniela Indenbirken, Jacqueline Nakel, Sanamjeet Virdi, Peter Bradtke, Niels Christian Lory, Michael Rothe, Maciej Paszkowski-Rogacz, Frank Buchholz, Adam Grundhoff, Axel Schambach, Christian Thirion, Hans-Willi Mittrücker, Julian Schulze Zur Wiesch, Joachim Hauber, Jan Chemnitz
Drug-based antiretroviral therapies (ART) efficiently suppress HIV replication in humans, but the virus persists as integrated proviral reservoirs in small numbers of cells. Importantly, ART cannot eliminate HIV from an infected individual, since it does not target the integrated provirus. Therefore, genome editing-based strategies that can inactivate or excise HIV genomes would provide the technology for novel curative therapies. In fact, the HIV-1 LTR-specific designer-recombinase Brec1 has been shown to remove integrated proviruses from infected cells and is highly efficacious on clinical HIV-1 isolates in vitro and in vivo, suggesting that Brec1 has the potential for clinical development of advanced HIV-1 eradication strategies in people living with HIV...
2024: PloS One
https://read.qxmd.com/read/38457227/strategies-to-target-the-central-nervous-system-hiv-reservoir
#23
JOURNAL ARTICLE
Andrea Mastrangelo, Lucio Gama, Paola Cinque
PURPOSE OF THE REVIEW: The central nervous system (CNS) is an hotspot for HIV persistence and may be a major obstacle to overcome for curative strategies. The peculiar anatomical, tissular and cellular characteristics of the HIV reservoir in the CNS may need to be specifically addressed to achieve a long-term HIV control without ART. In this review, we will discuss the critical challenges that currently explored curative strategies may face in crossing the blood-brain barrier (BBB), targeting latent HIV in brain-resident myeloid reservoirs, and eliminating the virus without eliciting dangerous neurological adverse events...
March 1, 2024: Current Opinion in HIV and AIDS
https://read.qxmd.com/read/38451208/post-cross-linked-ros-responsive-poly-%C3%AE-amino-ester-plasmid-polyplex-nps-for-gene-therapy-of-ebv-associated-nasopharyngeal-carcinoma
#24
JOURNAL ARTICLE
Caiyan Yuan, Shuangyan Chang, Chong Zhang, Dirong Dong, Jiahui Ding, Ali Reza Mahdavian, Zheng Hu, Lili Sun, Songwei Tan
Nasopharyngeal carcinoma (NPC) is one of the most common tumors in South China and Southeast Asia and is thought to be associated with Epstein-Barr virus (EBV) infection. Downregulation of latent membrane protein 1 (LMP1) encoded by EBV can reduce the expression of NF-κB and PI3K, induce apoptosis, and inhibit the growth of EBV-related NPC. For targeted cleavage of the Lmp1 oncogene via the CRISPR/Cas9 gene editing system, a post cross-linked ROS-responsive poly(β-amino ester) (PBAE) polymeric vector was developed for the delivery of CRISPR/Cas9 plasmids both in vitro and in vivo ...
March 7, 2024: Journal of Materials Chemistry. B, Materials for Biology and Medicine
https://read.qxmd.com/read/38450517/next-generation-strategies-to-improve-safety-and-efficacy-of-adeno-associated-virus-based-gene-therapy-for-hemophilia-lessons-from-clinical-trials-in-other-gene-therapies
#25
JOURNAL ARTICLE
Giovanni Di Minno, Wolfgang Miesbach, Giancarlo Castaman, Flora Peyvandi
Three major directions for the global progress of adeno-associated virus (AAV) vectors for gene therapies (GT) are analyzed: a) engineering vectors to increase transgene expression; b) aligning interests of the health system with costs and challenges for pharmaceutical industry; c) refining patient eligibility criteria, and endpoints definition. Currently employed AAV vectors may cause toxicity and adverse events. Furthermore, studies in animals do not fully predict risks and clinical benefits of AAV-based GT, and animal models reflecting the heterogeneity of certain clinical settings (e...
March 7, 2024: Haematologica
https://read.qxmd.com/read/38447647/a-virus-like-particle-candidate-vaccine-based-on-crispr-cas9-gene-editing-technology-elicits-broad-spectrum-protection-against-sars-cov-2
#26
JOURNAL ARTICLE
Weiqi Wang, Shen Wang, Xianyong Meng, Yongkun Zhao, Nan Li, Tiecheng Wang, Na Feng, Feihu Yan, Xianzhu Xia
The emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants with frequent mutations has seriously damaged the effectiveness of the 2019 coronavirus disease (COVID-19) vaccine. There is an urgent need to develop a broad-spectrum vaccine while elucidating the underlying immune mechanisms. Here, we developed a SARS-CoV-2 virus-like particles (VLPs) vaccine based on the Canarypox-virus vector (ALVAC-VLPs) using CRISPR/Cas9. Immunization with ALVAC-VLPs showed the effectively induce SARS-CoV-2 specific T and B cell responses to resist the lethal challenge of mouse adaptive strains...
March 4, 2024: Antiviral Research
https://read.qxmd.com/read/38440193/a-comprehensive-review-on-gossypium-hirsutum-resistance-against-cotton-leaf-curl-virus
#27
REVIEW
Sahar Nadeem, Syed Riaz Ahmed, Tahira Luqman, Daniel K Y Tan, Zahra Maryum, Khalid Pervaiz Akhtar, Sana Muhy Ud Din Khan, Muhammad Sayyam Tariq, Nazar Muhammad, Muhammad Kashif Riaz Khan, Yongming Liu
Cotton ( Gossypium hirsutum L.) is a significant fiber crop. Being a major contributor to the textile industry requires continuous care and attention. Cotton is subjected to various biotic and abiotic constraints. Among these, biotic factors including cotton leaf curl virus (CLCuV) are dominant. CLCuV is a notorious disease of cotton and is acquired, carried, and transmitted by the whitefly (Bemisia tabaci). A cotton plant affected with CLCuV may show a wide range of symptoms such as yellowing of leaves, thickening of veins, upward or downward curling, formation of enations, and stunted growth...
2024: Frontiers in Genetics
https://read.qxmd.com/read/38434025/hiv-1-proviral-dna-in-purified-peripheral-blood-cd34-stem-and-progenitor-cells-in-individuals-with-long-term-haart-paving-the-way-to-hiv-gene-therapy
#28
JOURNAL ARTICLE
Boonrat Tassaneetrithep, Angsana Phuphuakrat, Ekawat Pasomsub, Kanit Bhukhai, Wasinee Wongkummool, Thongkoon Priengprom, Wannisa Khamaikawin, Sujittra Chaisavaneeyakorn, Usanarat Anurathapan, Nopporn Apiwattanakul, Suradej Hongeng
Human immunodeficiency virus (HIV)-1 infection is an important public health problem worldwide. After primary HIV-1 infection, transcribed HIV-1 DNA is integrated into the host genome, serving as a reservoir of the virus and hindering a definite cure. Although highly active antiretroviral therapy suppresses active viral replication, resulting in undetectable levels of HIV RNA in the blood, a viral rebound can be detected after a few weeks of treatment interruption. This supports the concept that there is a stable HIV-1 reservoir in people living with HIV-1...
February 29, 2024: Heliyon
https://read.qxmd.com/read/38430229/assessing-immunogenicity-of-crispr-ncas9-engineered-strain-against-porcine-epidemic-diarrhea-virus
#29
JOURNAL ARTICLE
Fengsai Li, Haiyuan Zhao, Ling Sui, Fangjie Yin, Xinzi Liu, Guihai Guo, Jiaxuan Li, Yanping Jiang, Wen Cui, Zhifu Shan, Han Zhou, Li Wang, Xinyuan Qiao, Lijie Tang, Xiaona Wang, Yijing Li
Porcine epidemic diarrhea (PED) caused by porcine epidemic diarrhea virus (PEDV), is an acute and highly infectious disease, resulting in substantial economic losses in the pig industry. Given that PEDV primarily infects the mucosal surfaces of the intestinal tract, it is crucial to improve the mucosal immunity to prevent viral invasion. Lactic acid bacteria (LAB) oral vaccines offer unique advantages and potential applications in combatting mucosal infectious diseases, making them an ideal approach for controlling PED outbreaks...
March 2, 2024: Applied Microbiology and Biotechnology
https://read.qxmd.com/read/38428724/improved-antitumor-effects-elicited-by-an-oncolytic-hsv-1-expressing-a-novel-b7h3nb-cd3-bsab
#30
JOURNAL ARTICLE
Zongliang Zhang, Nian Yang, Huaqing Lu, Yongdong Chen, Long Xu, Zeng Wang, Qizhong Lu, Kunhong Zhong, Zhixiong Zhu, Guoqing Wang, Hexian Li, Meijun Zheng, Weiwei Zhang, Hui Yang, Xingchen Peng, Liangxue Zhou, Aiping Tong
Oncolytic viruses have emerged as a promising modality for cancer treatment due to their unique abilities to directly destroy tumor cells and modulate the tumor microenvironment. Bispecific T-cell engagers (BsAbs) have been developed to activate and redirect cytotoxic T lymphocytes, enhancing the antitumor response. To take advantage of the specific infection capacity and carrying ability of exogenous genes, we generated a recombinant herpes simplex virus type 1 (HSV-1), HSV-1dko -B7H3nb/CD3 or HSV-1dko -B7H3nb/mCD3, carrying a B7H3nb/CD3 or B7H3nb/mCD3 BsAb that replicates and expresses BsAb in tumor cells in vitro and in vivo...
February 28, 2024: Cancer Letters
https://read.qxmd.com/read/38422139/meat-from-gene-edited-pigs-could-hit-the-market
#31
Jon Cohen
United States and other countries may soon approve virus-proof pigs.
March 2024: Science
https://read.qxmd.com/read/38420830/mavs-ubiquitylation-function-mechanism-and-beyond
#32
REVIEW
Hongliang Dong, Jie Shen
The mitochondrial antiviral-signaling protein (MAVS), a core adaptor protein in the retinoic-acid-inducible gene-I-like receptors (RLRs)-MAVS pathway, has been demonstrated to play an important role in antiviral immune response and tumor immunology. Previous studies revealed that ubiquitylation is a key mechanism in the regulation of the RLRs-MAVS axis and immune response. Multiple E3 ubiquitin ligases and deubiquitinating enzymes control MAVS ubiquitylation and changes in MAVS function. In this review, we summarize the biological function of ubiquitylation in MAVS-related signaling and provide new insight into immunotherapy approaches that target MAVS...
February 21, 2024: Frontiers in Bioscience (Landmark Edition)
https://read.qxmd.com/read/38411080/crispr-cas9-screen-of-e3-ubiquitin-ligases-identifies-traf2-and-uhrf1-as-regulators-of-hiv-latency-in-primary-human-t-cells
#33
JOURNAL ARTICLE
Ujjwal Rathore, Paige Haas, Vigneshwari Easwar Kumar, Joseph Hiatt, Kelsey M Haas, Mehdi Bouhaddou, Danielle L Swaney, Erica Stevenson, Lorena Zuliani-Alvarez, Michael J McGregor, Autumn Turner-Groth, Charles Ochieng' Olwal, Yaw Bediako, Hannes Braberg, Margaret Soucheray, Melanie Ott, Manon Eckhardt, Judd F Hultquist, Alexander Marson, Robyn M Kaake, Nevan J Krogan
During HIV infection of CD4+ T cells, ubiquitin pathways are essential to viral replication and host innate immune response; however, the role of specific E3 ubiquitin ligases is not well understood. Proteomics analyses identified 116 single-subunit E3 ubiquitin ligases expressed in activated primary human CD4+ T cells. Using a CRISPR-based arrayed spreading infectivity assay, we systematically knocked out 116 E3s from activated primary CD4+ T cells and infected them with NL4-3 GFP reporter HIV-1. We found 10 E3s significantly positively or negatively affected HIV infection in activated primary CD4+ T cells, including UHRF1 (pro-viral) and TRAF2 (anti-viral)...
February 27, 2024: MBio
https://read.qxmd.com/read/38408137/therapeutic-in-vivo-gene-editing-achieved-by-a-hypercompact-crispr-cas12f1-system-delivered-with-all-in-one-adeno-associated-virus
#34
JOURNAL ARTICLE
Tongtong Cui, Bingyu Cai, Yao Tian, Xin Liu, Chen Liang, Qingqin Gao, Bojin Li, Yali Ding, Rongqi Li, Qi Zhou, Wei Li, Fei Teng
CRISPR-based gene therapies are making remarkable strides toward the clinic. But the large size of most widely used Cas endonucleases including Cas9 and Cas12a restricts their efficient delivery by the adeno-associated virus (AAV) for in vivo gene editing. Being exceptionally small, the recently engineered type V-F CRISPR-Cas12f1 systems can overcome the cargo packaging bottleneck and present as strong candidates for therapeutic applications. In this study, the pairwise editing efficiencies of different engineered Cas12f1/sgRNA scaffold combinations are systemically screened and optimized, and the CasMINI_v3...
February 26, 2024: Advanced Science (Weinheim, Baden-Wurttemberg, Germany)
https://read.qxmd.com/read/38407798/efficient-generation-of-crispr-cas9-mediated-knockout-human-primary-keratinocytes-by-electroporation
#35
JOURNAL ARTICLE
Tugay Karakaya, Marta Slaufova, Michela Di Filippo, Paulina Hennig, Gabriele Fenini, Thomas Kündig, Hans-Dietmar Beer
Due to their full differentiation capacity in vitro, the culture of human primary keratinocytes (HPKs) represents a physiological model for answering basic biological and dermatological research questions, including those related to skin diseases and the investigation of treatment options. When modified with the CRISPR/Cas9 gene editing approach and cultivated in organotypic 3D epidermal equivalents (EEs), these human cells have the potential to replace established mouse models. However, even when cultivated on feeder cells, HPKs have only a low proliferation capacity in 2D culture, limiting their application potential...
February 27, 2024: Methods in Molecular Biology
https://read.qxmd.com/read/38407550/engineering-anti-crispr-proteins-to-create-cas12a-protein-switches-for-activatable-genome-editing-and-viral-protease-detection
#36
JOURNAL ARTICLE
Wenyuan Kang, Fei Xiao, Xi Zhu, Xinyu Ling, Shiyi Xie, Ruimiao Li, Peihang Yu, Linxin Cao, Chunyang Lei, Ye Qiu, Tao Liu, Zhou Nie
Proteins capable of switching between distinct active states in response to biochemical cues are ideal for sensing and controlling biological processes. Activatable CRISPR-Cas systems are significant in precise genetic manipulation and sensitive molecular diagnostics, yet directly controlling Cas protein function remains challenging. Herein, we explore anti-CRISPR (Acr) proteins as modules to create synthetic Cas protein switches (CasPSs) based on computational chemistry-directed rational protein interface engineering...
February 26, 2024: Angewandte Chemie
https://read.qxmd.com/read/38405747/virus-free-crispr-knock-in-of-a-chimeric-antigen-receptor-into-klrc1-generates-potent-gd2-specific-natural-killer-cells
#37
Keerthana Shankar, Isabella Zingler-Hoslet, Lei Shi, Varun Katta, Brittany E Russell, Shengdar Q Tsai, Christian M Capitini, Krishanu Saha
Natural killer (NK) cells are an appealing off-the-shelf, allogeneic cellular therapy due to their cytotoxic profile. However, their activity against solid tumors remains suboptimal in part due to the upregulation of NK-inhibitory ligands, such as HLA-E, within the tumor microenvironment. Here, we utilize CRISPR-Cas9 to disrupt the KLRC1 gene (encoding the HLA-E-binding NKG2A receptor) and perform non-viral insertion of a GD2-targeting chimeric antigen receptor (CAR) within NK cells isolated from human peripheral blood...
February 14, 2024: bioRxiv
https://read.qxmd.com/read/38403027/crkl-dictates-anti-pd-1-resistance-by-mediating-tumor-associated-neutrophil-infiltration-in-hepatocellular-carcinoma
#38
JOURNAL ARTICLE
Peiyi Xie, Mincheng Yu, Bo Zhang, Qiang Yu, Yufei Zhao, Mengyuan Wu, Lei Jin, Jiuliang Yan, Binghai Zhou, Shuang Liu, Xiaoqiang Li, Chenhao Zhou, Xiaodong Zhu, Cheng Huang, Yongfeng Xu, Yongsheng Xiao, Jian Zhou, Jia Fan, Mien-Chie Hung, Qinghai Ye, Lei Guo, Hui Li
BACKGROUND & AIMS: Immune checkpoint inhibitors (ICIs) resistance limits immunotherapy success in hepatocellular carcinoma (HCC). However, the mechanisms underlying immunotherapy resistance remain elusive. We aimed to identify the role of CT10 regulator of kinase-like (CRKL) in HCC against anti-PD-1 therapy. METHODS: Gene expression in HCC specimens from 10 patients accepted anti-PD-1 therapy was identified by RNA-sequencing. A total of 342 and 62 HCC samples from TMA1 and TMA2, respectively, were analyzed by immunohistochemistry...
February 23, 2024: Journal of Hepatology
https://read.qxmd.com/read/38400086/application-of-crispr-cas9-for-rapid-genome-editing-of-pseudorabies-virus-and-bovine-herpesvirus-1
#39
JOURNAL ARTICLE
Wanqi Yu, Jingyi Liu, Yingnan Liu, Maria Forlenza, Hongjun Chen
The CRISPR/Cas9 system is widely used to manipulate viral genomes. Although Alphaherpesvirinae genomes are large and complicated to edit, in recent years several Pseudorabies virus (PRV) mutants have been successfully generated using the CRISPR/Cas9 system. However, the application of CRISPR/Cas9 editing on another member of alpha herpesviruses, bovine herpesvirus-1 (BHV-1), is rarely reported. This paper reports a rapid and straightforward approach to manipulating herpesviruses genome using CRISPR/Cas9. The recombinant plasmids contained the left and right arm of the thymidine kinase ( TK ) gene of PRV or of the glycoprotein I ( gI ) and glycoprotein E ( gE ) of BHV-1...
February 18, 2024: Viruses
https://read.qxmd.com/read/38399958/epigenetic-restriction-factors-erfs-in-virus-infection
#40
REVIEW
Arunava Roy, Anandita Ghosh
The ongoing arms race between viruses and their hosts is constantly evolving. One of the ways in which cells defend themselves against invading viruses is by using restriction factors (RFs), which are cell-intrinsic antiviral mechanisms that block viral replication and transcription. Recent research has identified a specific group of RFs that belong to the cellular epigenetic machinery and are able to restrict the gene expression of certain viruses. These RFs can be referred to as epigenetic restriction factors or eRFs...
January 25, 2024: Viruses
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