140,349 results match your criteria gene targeting

Systemic delivery of CRISPR/Cas9 to hepatic tumors for cancer treatment using altered tropism of lentiviral vector.

Biomaterials 2021 Apr 1;272:120793. Epub 2021 Apr 1.

Center for Theragnosis, Biomedical Research Institute, Korea Institute of Science and Technology, Seoul, South Korea. Electronic address:

Therapeutic application of CRISPR/Cas9 nucleases remains a challenge due to the lack of efficient in vivo delivery carriers. Here, we examine the ability of lentiviral vectors pseudotyped with hepatitis C virus (HCV)/E1E2 envelope glycoproteins to systemically deliver CRISPR/Cas9 to hepatic tumors in vivo. We demonstrated that systemic administration of E1E2-pseudotyped lentiviral vectors can selectively deliver Cas9 and sgRNA specific for kinesin spindle protein (KSP) to Huh7 tumors in the orthotopic Huh7 mice due to the specific interactions between E1E2 and their cellular receptors. Read More

View Article and Full-Text PDF

Tumor suppressor gene DLC1: Its modification, interactive molecules, and potential prospects for clinical cancer application.

Int J Biol Macromol 2021 Apr 6. Epub 2021 Apr 6.

Shandong Provincial Key Laboratory of Animal Resistant, School of Life Sciences, Shandong Normal University, Jinan, China. Electronic address:

Deleted in liver cancer 1 (DLC1) is a recognized tumor suppressor gene that negatively regulates Rho family proteins by hydrolyzing the active GTP-bound state to its inactive GDP-bound state. Active Rho proteins play a positive role in tumorigenesis. Numerous in vitro and in vivo experiments have shown that DLC1 is downregulated or inactivated in various solid tumors, which may be due to the following five reasons: genomic deletion, epigenetic modification, and ubiquitin-dependent proteasomal degradation may cause DLC1 underexpression; phosphorylation at the post-translation level may cause DLC1 inactivation; and failure to localize at focal adhesions (FAs) may prevent DLC1 from exerting full activity. Read More

View Article and Full-Text PDF

Development of p53 Knockout U87MG Cell Line for Unbiased Drug Delivery Testing System Using CRISPR-Cas9 and Transcriptomic Analysis.

J Biotechnol 2021 Apr 6. Epub 2021 Apr 6.

RIKEN Center for Integrative Medical Sciences, Japan. Electronic address:

Antibody-drug conjugates offers many advantages as a drug delivery platform that allows for highly specific targeting of cell types and genes. Ideally, testing the efficacy of these systems requires two cell types to be different only in the gene targeted by the drug, with the rest of the cellular machinery unchanged, in order to minimize other potential differences from obscuring the effects of the drug. In this study, we created multiple variants of U87MG cells with targeted mutation in the TP53 gene using the CRISPR-Cas9 system, and determined that their major transcriptional differences stem from the loss of p53 function. Read More

View Article and Full-Text PDF

Chlamydomonas POLQ is necessary for CRISPR/Cas9-mediated gene targeting.

G3 (Bethesda) 2021 Apr 9. Epub 2021 Apr 9.

Institute of Biology, Experimental Biophysics, Humboldt University of Berlin, Berlin, Germany, D-10099.

The use of CRISPR/Cas endonucleases has revolutionized gene editing techniques for research on Chlamydomonas reinhardtii. To better utilize the CRISPR/Cas system, it is essential to develop a more comprehensive understanding of the DNA repair pathways involved in genome editing. In this study, we have analyzed contributions from canonical KU80/KU70-dependent non-homologous end-joining and polymerase theta (POLQ)-mediated end-joining on SpCas9-mediated untemplated mutagenesis and homology-directed repair/gene inactivation in Chlamydomonas. Read More

View Article and Full-Text PDF

Targeting Chikungunya Virus Replication by Benzoannulene Inhibitors.

J Med Chem 2021 Apr 9. Epub 2021 Apr 9.

Drug Discovery Division, Southern Research, 2000 Ninth Avenue South, Birmingham, Alabama 35205, United States.

A benzo[6]annulene, 4-(-butyl)--(3-methoxy-5,6,7,8-tetrahydronaphthalen-2-yl) benzamide (), was identified as an inhibitor against Chikungunya virus (CHIKV) with antiviral activity EC = 1.45 μM and viral titer reduction (VTR) of 2.5 log at 10 μM with no observed cytotoxicity (CC = 169 μM) in normal human dermal fibroblast cells. Read More

View Article and Full-Text PDF

CRISPR/Cas: a Nobel Prize award-winning precise genome editing technology for gene therapy and crop improvement.

J Zhejiang Univ Sci B 2021 Apr;22(4):253-284

Department of Biology, East Carolina University, Greenville, NC 27858, USA.

Since it was first recognized in bacteria and archaea as a mechanism for innate viral immunity in the early 2010s, clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein (Cas) has rapidly been developed into a robust, multifunctional genome editing tool with many uses. Following the discovery of the initial CRISPR/Cas-based system, the technology has been advanced to facilitate a multitude of different functions. These include development as a base editor, prime editor, epigenetic editor, and CRISPR interference (CRISPRi) and CRISPR activator (CRISPRa) gene regulators. Read More

View Article and Full-Text PDF

Extracellular vesicle-derived microRNA-18b ameliorates preeclampsia by enhancing trophoblast proliferation and migration via Notch2/TIM3/mTORC1 axis.

J Cell Mol Med 2021 Apr 9. Epub 2021 Apr 9.

Department of Obstetrics and Gynecology, Sichuan Academy of Medical Sciences & Sichuan Provincial People's Hospital, Chengdu, China.

Preeclampsia (PE), a common disorder of pregnancy, is characterized by insufficient trophoblast migration and inadequate vascular remodelling, such that promotion of trophoblast proliferation might ameliorate PE. In the current study, we sought to study the underlying mechanism of extracellular vesicle (EV)-derived microRNA-18 (miR-18b) in PE. Human umbilical cord mesenchymal stem cells (HUCMSCs) isolated from placental tissues were verified through osteogenic, adipogenic and chondrogenic differentiation assays. Read More

View Article and Full-Text PDF

Application of portable real-time recombinase-aided amplification (rt-RAA) assay in the clinical diagnosis of ASFV and prospective DIVA diagnosis.

Appl Microbiol Biotechnol 2021 Apr 9. Epub 2021 Apr 9.

Beijing Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Beijing, 100193, China.

African swine fever, a serious infectious disease, has been found in many countries around the world over the last nearly 100 years, and causes untold damage to the economy wherever it occurs. Diagnosis is currently performed by real-time PCR, which is highly sensitive but can only be carried out in a diagnostic laboratory environment with sophisticated equipment and expertise. A sensitive, rapid diagnostic method that can be implemented in agricultural settings is thus urgently needed for the detection and control of African swine fever virus (ASFV) infection. Read More

View Article and Full-Text PDF

Presence and shedding of in waterfowl in a rehabilitation facility and in the wild in New Zealand.

N Z Vet J 2021 Apr 9:1-15. Epub 2021 Apr 9.

Tāwharau Ora, School of Veterinary Science, Massey University, Palmerston North 4410, New Zealand.

Aims: To determine the frequency of infection, shedding dynamics of and genotype diversity in waterfowl temporarily resident in a rehabilitation facility and in mallards in the wild.

Methods: Conjunctival-choanal-cloacal swabs were collected from apparently healthy captive wild mallards (; n=114) and paradise shelducks (; n=10) temporarily housed at a waterfowl breeding and rehabilitation facility (Wellington, NZ) and from wild mallards in Palmerston North (n=50), and Southland (n=50). DNA extracted from the swabs was analysed using quantitative PCR (qPCR) high-resolution melt curve (HRM) analysis, targeting the gene of

Results: Of the captive waterfowl, 39/114 (34%) mallards and 6/10 (60%) paradise shelducks were positive for as were 24/100 (24%) of wild mallards. Read More

View Article and Full-Text PDF

New 24-Membered Macrolactins Isolated from Marine Bacteria as Potent Fungal Inhibitors against Sugarcane Smut.

J Agric Food Chem 2021 Apr 9. Epub 2021 Apr 9.

Institute of Marine Drugs, School of Pharmaceutical Sciences, Guangxi Key Laboratory of Efficacy Study on Chinese Materia Medica, Guangxi University of Chinese Medicine, NO. 13 Wuhe Rood, Nanning 530200, China.

Sugarcane smut, caused by , is one of the most devastating fungal diseases affecting sugarcane worldwide. To develop a potent sugarcane smut fungicide, secondary metabolites of marine-derived were isolated and screened for inhibitory activities, which led to the discovery of five new 24-membered macrolactins, bamemacrolactins A-E (-), with being the most potent inhibitor. The antifungal mechanism of was studied by assessing its effects on mycelial morphology and the cell wall. Read More

View Article and Full-Text PDF

The Genetic Basis of Reporter Mouse Strains.

Adv Exp Med Biol 2021 ;1310:551-564

Department of Medical Science and Asan Medical Institute of Convergence Science and Technology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea.

Genetically engineered mouse (GEM) models have been revolutionizing the biomedical studies on deciphering the physiological roles of genes in vivo. In addition to deactivating a gene in mice, diverse strategies have been created to monitor gene expressions and molecular dynamics of specific proteins in vivo. Although gene targeting in mouse embryonic stem (ES) cells was essential for the precise engineering of the mouse genome over almost three decades, this process is a time-consuming, expensive, and laborious one. Read More

View Article and Full-Text PDF
January 2021

Osteosarcoma Cell-Derived Exosomal miR-1307 Promotes Tumorgenesis via Targeting AGAP1.

Biomed Res Int 2021 25;2021:7358153. Epub 2021 Mar 25.

Department of Orthopaedics, The First Affiliated Hospital of the Medical College, Shihezi University, Shihezi, China.

The occurrence of osteosarcoma (OS) is associated with abnormal expression of many microRNAs (miRNAs). Exosomal miRNAs get much more attentions in intracellular communications. miR-1307 has been studied in many cancers, but its effects in OS have not been studied. Read More

View Article and Full-Text PDF

Can Targeting Iron Help in Combating Chronic Pseudomonas Infection? A Systematic Review.

Cureus 2021 Mar 5;13(3):e13716. Epub 2021 Mar 5.

Internal Medicine, California Institute of Behavioral Neurosciences & Psychology, Fairfield, USA.

Cystic fibrosis is an autosomal recessive disorder caused by a mutation in genes for cystic fibrosis transmembrane conductance regulator (CFTR) protein. CFTR gene is responsible for the production of sweat, digestive fluids, and mucus, and any mutation in this would lead to the thickening of these secretions. Cystic fibrosis is a multi-organ disorder, but 80% of patients suffer from respiratory problems due to chronic infections most commonly caused by . Read More

View Article and Full-Text PDF

Mir-184 Contributes to Brain Injury Through Targeting PPAP2B Following Ischemic Stroke in Male Rats.

Front Mol Neurosci 2021 23;14:613887. Epub 2021 Mar 23.

Department of Respiratory Medicine, The First People's Hospital of Zunyi, The Third Affiliated Hospital of Zunyi Medical University, Zunyi, China.

Our previous study revealed that miR-184 expression is significantly altered in the brain following ischemic stroke in rats. However, it is unknown whether this alteration in miR-184 expression contributes to brain injury after ischemic stroke. Here, we aim to address the potential of miR-184 to impact nerve injury following ischemia and reperfusion. Read More

View Article and Full-Text PDF

LncRNA LHFPL3-AS1 Promotes Oral Squamous Cell Carcinoma Growth and Cisplatin Resistance Through Targeting miR-362-5p/CHSY1 Pathway.

Onco Targets Ther 2021 31;14:2293-2300. Epub 2021 Mar 31.

Department of Stomatology, Shenzhen Longhua District Central Hospital, Shenzhen, 518000, People's Republic of China.

Background: Oral squamous cell carcinoma (OSCC) is a common oral cancer. The current study aims to elucidate the potential roles of long noncoding RNA (lncRNA) LHFPL3-AS1 in OSCC development.

Methods: Gene expression was measured by qRT-PCR in tumor tissues and cell lines. Read More

View Article and Full-Text PDF

Nucleolin-Targeting AS1411 Aptamer-Modified Micelle for the Co-Delivery of Doxorubicin and miR-519c to Improve the Therapeutic Efficacy in Hepatocellular Carcinoma Treatment.

Int J Nanomedicine 2021 30;16:2569-2584. Epub 2021 Mar 30.

Key Laboratory for Molecular Enzymology and Engineering of Ministry of Education, School of Life Sciences, Jilin University, Changchun, 130012, People's Republic of China.

Background: Multidrug resistance (MDR) has emerged to be a major hindrance in cancer therapy, which contributes to the reduced sensitivity of cancer cells toward chemotherapeutic drugs mainly owing to the over-expression of drug efflux transporters. The combination of gene therapy and chemotherapy has been considered as a potential approach to improve the anti-cancer efficacy by reversing the MDR effect.

Materials And Methods: The AS1411 aptamer-functionalized micelles were constructed through an emulsion/solvent evaporation strategy for the simultaneous co-delivery of doxorubicin and miR-519c. Read More

View Article and Full-Text PDF

Investigation into molecular mechanisms and high-frequency core TCM for pulmonary fibrosis secondary to COVID-19 based on network pharmacology and data mining.

Ann Palliat Med 2021 Apr 1. Epub 2021 Apr 1.

Department of Pharmacy, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China.

Background: The complication, pulmonary fibrosis (PF) secondary to COVID-19, may have a second wave of late mortality, given the huge number of individuals infected by COVID-19. However, the molecular mechanisms of PF secondary to COVID-19 haven't been fully elucidated, making the identification of novel strategies for targeted therapy challenging. This study aimed to systematically identify the molecular mechanisms and high-frequency core traditional Chinese medicine (TCM) targeting PF secondary to COVID-19 through network pharmacology and data mining. Read More

View Article and Full-Text PDF

Decitabine combined with medium-dose cytarabine in the treatment of DEK/CAN-positive acute myeloid leukemia: a case report.

Ann Palliat Med 2021 Apr 1. Epub 2021 Apr 1.

Department of Neurosurgery, The First Affiliated Hospital of Nanchang University, Nanchang, China.

Acute myeloid leukemia (AML) is a malignant clonal hematopoietic stem cell disease. Although there are many therapeutic options, it is still an incurable hematological malignancy. Moreover, the prognosis of AML is closely related to its cytogenetics and molecular biology. Read More

View Article and Full-Text PDF

MicroRNA-496 inhibits triple negative breast cancer cell proliferation by targeting Del-1.

Medicine (Baltimore) 2021 Apr;100(14):e25270

Department of Oncology/Hematology, School of Medicine, Kyungpook National University, Kyungpook National University Chilgok Hospital.

Abstract: Del-1 has been linked to the pathogenesis of various cancers, including breast cancer. However, the regulation of Del-1 expression remains unclear. We previously reported the interaction between microRNA-137 (miR-137) and the Del-1 gene. Read More

View Article and Full-Text PDF

The uncharacterized SANT and BTB domain-containing protein SANBR inhibits class switch recombination.

J Biol Chem 2021 Apr 5:100625. Epub 2021 Apr 5.

Department of Biology, The Graduate Center and The City College of New York, New York, NY, 10031, USA. Electronic address:

Class switch recombination (CSR) is the process by which B cells switch production from IgM/IgD to other immunoglobulin isotypes, enabling them to mount an effective immune response against pathogens. Timely resolution of CSR prevents damage due to an uncontrolled and prolonged immune response. While many positive regulators of CSR have been described, negative regulators of CSR are relatively unknown. Read More

View Article and Full-Text PDF

n4 The utilisation of CytB and COI barcodes for the identification of bloodmeals and Culicoides species (Diptera: Ceratopogonidae) reveals a variety of novel wildlife hosts in South Africa.

Acta Trop 2021 Apr 5:105913. Epub 2021 Apr 5.

Centre for Viral Zoonoses, Department Medical Virology, Faculty of Health Science, University of Pretoria, Pretoria, South Africa. Electronic address:

Biting midges in the genus Culicoides (Diptera; Ceratopogonidae) are vectors of pathogens that can cause diseases of major economic importance in humans and animals. Identifying host ranges of these biting midges might aid in understanding the complex epidemiology of such diseases, often involving reservoirs hosts and multiple species. In this study, we aim to identify bloodmeal origin from engorged female Culicoides biting midges. Read More

View Article and Full-Text PDF

Induction of PDCD4 by albumin in proximal tubule epithelial cells potentiates proteinuria-induced dysfunctional autophagy by negatively targeting Atg5.

Biochem Cell Biol 2021 Apr 8. Epub 2021 Apr 8.

Xian Jiaotong University, 12480, Biochemistry and Molecular Biology, Xi'an, Shaanxi, China.

The precise molecular mechanism of autophagy dysfunction in type 1 diabetes is not known. Herein, the role of programmed cell death 4 (PDCD4) in autophagy regulation in the pathogenesis of diabetic kidney disease (DKD) in vivo and in vitro was described. It was found that Pdcd4 mRNA and protein was upregulated in the streptozotocin (STZ)-induced DKD rats. Read More

View Article and Full-Text PDF

Targeting Gys1 with AAV-SaCas9 Decreases Pathogenic Polyglucosan Bodies and Neuroinflammation in Adult Polyglucosan Body and Lafora Disease Mouse Models.

Neurotherapeutics 2021 Apr 8. Epub 2021 Apr 8.

Division of Neurology, Department of Pediatrics, University of Texas Southwestern Medical Center, Dallas, TX, 75390, USA.

Many adult and most childhood neurological diseases have a genetic basis. CRISPR/Cas9 biotechnology holds great promise in neurological therapy, pending the clearance of major delivery, efficiency, and specificity hurdles. We applied CRISPR/Cas9 genome editing in its simplest modality, namely inducing gene sequence disruption, to one adult and one pediatric disease. Read More

View Article and Full-Text PDF

Species composition and infection levels of Anisakis (Nematoda: Anisakidae) in the skipjack tuna Katsuwonus pelamis (Linnaeus) in the Northwest Pacific.

Parasitol Res 2021 Apr 8. Epub 2021 Apr 8.

Meguro Parasitological Museum, Meguro, Tokyo, Japan.

Parasites can be used as biological tags to assess stock structures in various marine fish species. In the present study, the species composition and infection levels of parasitic nematodes of the genus Anisakis in the skipjack tuna Katsuwonus pelamis were examined in the Northwest Pacific and adjacent seas. A total of 867 third-stage larvae of Anisakis were collected from 112 skipjack tunas captured around Japan and in other subtropical localities. Read More

View Article and Full-Text PDF

miR-122 promotes virus-induced lung disease by targeting SOCS1.

JCI Insight 2021 Apr 8;6(7). Epub 2021 Apr 8.

Priority Research Centre GrowUpWell, Experimental and Translational Respiratory Medicine Group, School of Medicine and Public Health, University of Newcastle, Newcastle, New South Wales, Australia.

Virus-induced respiratory tract infections are a major health burden in childhood, and available treatments are supportive rather than disease modifying. Rhinoviruses (RVs), the cause of approximately 80% of common colds, are detected in nearly half of all infants with bronchiolitis and the majority of children with an asthma exacerbation. Bronchiolitis in early life is a strong risk factor for the development of asthma. Read More

View Article and Full-Text PDF

KDM5B promotes self-renewal of hepatocellular carcinoma cells through the microRNA-448-mediated YTHDF3/ITGA6 axis.

J Cell Mol Med 2021 Apr 7. Epub 2021 Apr 7.

Hainan General Hospital, Haikou, China.

Histone methylation plays important roles in mediating the onset and progression of various cancers, and lysine-specific demethylase 5B (KDM5B), as a histone demethylase, is reported to be an oncogene in hepatocellular carcinoma (HCC). However, the mechanism underlying its tumorigenesis remains undefined. Hence, we explored the regulatory role of KDM5B in HCC cells, aiming to identify novel therapeutic targets for HCC. Read More

View Article and Full-Text PDF

The role of EBV in hematolymphoid proliferations: Emerging concepts relevant to diagnosis and treatment.

Histopathology 2021 Apr 7. Epub 2021 Apr 7.

Robert J. Tomsich Pathology and Laboratory Medicine Institute, Department of Laboratory Medicine, Cleveland Clinic, Cleveland, OH, USA.

Epstein-Barr virus (EBV) is a ubiquitous gammaherpesvirus with >90% of the adult population worldwide harboring latent infection. A small subset of those infected develop EBV-associated neoplasms including a range of lymphoproliferative disorders (LPD). The diagnostic distinction of these entities appears increasingly relevant as our understanding of EBV-host interactions and mechanisms of EBV-driven lymphomagenesis improves. Read More

View Article and Full-Text PDF

Multidimensional Intersection of Nicotine, Gene Expression, and Behavior.

Front Behav Neurosci 2021 22;15:649129. Epub 2021 Mar 22.

Department of Neurobiology and Behavior, University of California, Irvine, Irvine, CA, Unites States.

The cholinergic system plays a crucial role in nervous system function with important effects on developmental processes, cognition, attention, motivation, reward, learning, and memory. Nicotine, the reinforcing component of tobacco and e-cigarettes, directly acts on the cholinergic system by targeting nicotinic acetylcholine receptors (nAChRs) in the brain. Activation of nAChRs leads to a multitude of immediate and long-lasting effects in specific cellular populations, thereby affecting the addictive properties of the drug. Read More

View Article and Full-Text PDF

MiR-485 targets the DTX4 gene to regulate milk fat synthesis in bovine mammary epithelial cells.

Sci Rep 2021 Apr 7;11(1):7623. Epub 2021 Apr 7.

College of Coastal Agricultural Sciences, Guangdong Ocean University, Zhanjiang, 524088, Guangdong, People's Republic of China.

MicroRNAs (miRNAs) are mRNA suppressors that regulate a variety of cellular and physiological processes, including cell proliferation, apoptosis, triglyceride synthesis, fat formation, and lipolysis, by post-transcriptional processing. In previous studies, we isolated and sequenced miRNAs from mammary epithelial cells from Chinese Holstein cows with high and low milk fat percentages. MiR-485 was one of the significantly differentially expressed miRNAs that were identified. Read More

View Article and Full-Text PDF

Widespread and sustained target engagement in Huntington's disease minipigs upon intrastriatal microRNA-based gene therapy.

Sci Transl Med 2021 Apr;13(588)

Department of Research and Development, uniQure biopharma B.V., Paasheuvelweg 25a, 1105 BP Amsterdam, Netherlands.

Huntingtin (HTT)-lowering therapies hold promise to slow down neurodegeneration in Huntington's disease (HD). Here, we assessed the translatability and long-term durability of recombinant adeno-associated viral vector serotype 5 expressing a microRNA targeting human (rAAV5-miHTT) administered by magnetic resonance imaging-guided convention-enhanced delivery in transgenic HD minipigs. rAAV5-miHTT (1. Read More

View Article and Full-Text PDF