47,272 results match your criteria transgene

Influence of the shared epitope on the elicitation of experimental autoimmune arthritis biomarkers.

PLoS One 2021 15;16(4):e0250177. Epub 2021 Apr 15.

Memphis VA Medical Center, Memphis, TN, United States of America.

Our previous studies have shown that inoculation of the oral cavity of "humanized" B6.DR1/4 mice with the periodontal pathogen Porphyromonas gingivalis results in an increase in the percentage of circulating Th17 cells, loss of bone and an exacerbation of experimental autoimmune arthritis. The aim of this study was to assess the role played by the human HLA-DRβ molecule containing the shared epitope supplied as a transgene to I-A˚ (murine class II null) C57BL/6 (B6) mice in driving these findings. Read More

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Two-pronged pulmonary gene delivery strategy: a surface-modified fullerene nanoparticle and a hypotonic vehicle.

Angew Chem Int Ed Engl 2021 Apr 14. Epub 2021 Apr 14.

Johns Hopkins University, 400 N. Broadway, Smith Building 6029, 21231, Baltimore, UNITED STATES.

Inhaled gene therapy poses a unique potential of curing chronic lung diseases which are currently managed primarily by symptomatic treatments. However, it has been challenging to achieve therapeutically-relevant gene transfer efficacy in the lung thus far due to the presence of numerous biological delivery barriers. Here, we introduce a simple combinatorial approach that overcomes both extracellular and cellular barriers to enhance gene transfer efficacy in the lung in vivo . Read More

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Novel transgenic mice with Cre-dependent co-expression of GFP and human ACE2: a safe tool for study of COVID-19 pathogenesis.

Transgenic Res 2021 Apr 14. Epub 2021 Apr 14.

Center for Precision Genome Editing and Genetic Technologies for Biomedicine, Institute of Gene Biology, Russian Academy of Sciences, Vavilova st. 34/5, Moscow, Russian Federation, 119334.

The current coronavirus disease (COVID-19) pandemic remains one of the most serious public health problems. Increasing evidence shows that infection by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) causes a very complex and multifaceted disease that requires detailed study. Nevertheless, experimental research on COVID-19 remains challenging due to the lack of appropriate animal models. Read More

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Molecular and Electrophysiological Characterization of Dorsal Horn Neurons in a GlyT2-iCre-tdTomato Mouse Line.

J Pain Res 2021 7;14:907-921. Epub 2021 Apr 7.

Department of Pain Medicine.

Purpose: Spinal glycinergic neurons function as critical elements of a spinal gate for pain and itch. We have recently documented that spinal PKCγ neurons receive the feedforward inhibitory input driven by Aβ primary afferent. The glycinergic neurons control the excitability of PKCγ neurons and therefore gate mechanical allodynia. Read More

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A nonviral, nonintegrating DNA nanovector platform for the safe, rapid, and persistent manufacture of recombinant T cells.

Sci Adv 2021 Apr 14;7(16). Epub 2021 Apr 14.

DNA Vector Laboratory, DKFZ Heidelberg, Im Neuenheimer Feld 242, Heidelberg, Germany.

The compelling need to provide adoptive cell therapy (ACT) to an increasing number of oncology patients within a meaningful therapeutic window makes the development of an efficient, fast, versatile, and safe genetic tool for creating recombinant T cells indispensable. In this study, we used nonintegrating minimally sized DNA vectors with an enhanced capability of generating genetically modified cells, and we demonstrate that they can be efficiently used to engineer human T lymphocytes. This vector platform contains no viral components and is capable of replicating extrachromosomally in the nucleus of dividing cells, providing persistent transgene expression in human T cells without affecting their behavior and molecular integrity. Read More

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Exploration of p53 plus interferon-beta gene transfer for the sensitization of human colorectal cancer cell lines to cell death.

Cancer Biol Ther 2021 Apr 14:1-10. Epub 2021 Apr 14.

Laboratório De Vetores Virais, Centro De Investigação Translacional Em Oncologia/LIM24, Instituto Do Câncer Do Estado De São Paulo, Faculdade De Medicina, Universidade De São Paulo, São Paulo, Brazil.

While treatments for colorectal cancer continue to improve, some 50% of patients succumb within 5 years, pointing to the need for additional therapeutic options. We have developed a modified non-replicating adenoviral vector for gene transfer, called AdRGD-PG, which offers improved levels of transduction and transgene expression. Here, we employ the p53-responsive PG promoter to drive expression of p53 or human interferon-β (hIFNβ) in human colorectal cancer cell lines HCT116 (wtp53), HCT116 (p53 deficient) and HT29 (mutant p53). Read More

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Generation of a new mouse line with conditionally activated signaling through the BMP receptor, ACVR1: A tool to characterize pleiotropic roles of BMP functions.

Genesis 2021 Apr 14:e23419. Epub 2021 Apr 14.

Department of Biologic and Materials Sciences & Prosthodontics, School of Dentistry, University of Michigan, MI, USA.

BMP signaling plays pleiotropic roles in various tissues during embryogenesis and after birth. We have previously generated a constitutively activated Acvr1(ca-Acvr1) transgenic mouse line (line L35) through pronuclei injection to investigate impacts of enhanced BMP signaling in a tissue specific manner. However, line L35 shows a restricted expression pattern of the transgene. Read More

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Advances and challenges in adeno-associated viral inner-ear gene therapy for sensorineural hearing loss.

Mol Ther Methods Clin Dev 2021 Jun 10;21:209-236. Epub 2021 Mar 10.

Department of Otorhinolaryngology, Head and Neck Surgery, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.

There is growing attention and effort focused on treating the root cause of sensorineural hearing loss rather than managing associated secondary characteristic features. With recent substantial advances in understanding sensorineural hearing-loss mechanisms, gene delivery has emerged as a promising strategy for the biological treatment of hearing loss associated with genetic dysfunction. There are several successful and promising proof-of-principle examples of transgene deliveries in animal models; however, there remains substantial further progress to be made in these avenues before realizing their clinical application in humans. Read More

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Novel Wx alleles generated by base editing for improvement of rice grain quality.

J Integr Plant Biol 2021 Apr 13. Epub 2021 Apr 13.

School of Life Sciences, Shandong Normal University, Ji'nan, 250014, China.

Amylose content (AC), which is regulated by the Waxy (Wx) gene, is a major indicator of eating and cooking quality in rice (Oryza sativa). Thus far, only a limited number of mutations in the N-terminal domain of Wx were found to have a major impact on the AC of rice grains and no mutations with such effects were reported for other regions of the Wx protein. Here, nucleotide substitutions in the middle region of Wx were generated by adenine and cytosine base editors. Read More

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Therapeutic B-cell depletion reverses progression of Alzheimer's disease.

Nat Commun 2021 04 12;12(1):2185. Epub 2021 Apr 12.

Immunoregulation Section, Laboratory of Immunology and Molecular Biology, National Institute on Aging, Baltimore, MD, USA.

The function of B cells in Alzheimer's disease (AD) is not fully understood. While immunoglobulins that target amyloid beta (Aβ) may interfere with plaque formation and hence progression of the disease, B cells may contribute beyond merely producing immunoglobulins. Here we show that AD is associated with accumulation of activated B cells in circulation, and with infiltration of B cells into the brain parenchyma, resulting in immunoglobulin deposits around Aβ plaques. Read More

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Anthocyanin synthesis in orange carrot cv. Danvers is activated by transgene expression of the transcription factors DcMYB113_NB and DcEGL1_NB from black carrot cv. Nightbird.

Plant Mol Biol 2021 Apr 9. Epub 2021 Apr 9.

Department of Agroecology, Aarhus University, Research Center Flakkebjerg, DK-4200, Aarhus C, Denmark.

Black carrots are potent sources of anthocyanin for the natural food color industry as their anthocyanins contain very high percentages of acylated anthocyanins which are much more stable than non-acylated anthocyanins. Anthocyanins are synthesized by a specific branch of the phenylpropanoid pathway activated by a triad of R2R3-MYB, bHLH and WD40 transcription factors (TFs). Recent studies in black carrots have elucidated major anthocyanin related structural genes and also regulatory TFs. Read More

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Investigating the effects of IDO1, PTGS2, and TGF-β1 overexpression on immunomodulatory properties of hTERT-MSCs and their extracellular vesicles.

Sci Rep 2021 Apr 9;11(1):7825. Epub 2021 Apr 9.

Department of Biology, Faculty of Science, Ferdowsi University of Mashhad, Mashhad, Khorasan Razavi, Iran.

The therapeutic potential of mesenchymal stem cells (MSCs) is out of the question. Yet, recent drawbacks have resulted in a strategic shift towards the application of MSC-derived cell-free products such as extracellular vesicles (EVs). Recent reports revealed that functional properties of MSCs, including EV secretion patterns, correlate with microenvironmental cues. Read More

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The unicellular red alga Cyanidioschyzon merolae - the simplest model of a photosynthetic eukaryote.

Plant Cell Physiol 2021 Apr 9. Epub 2021 Apr 9.

Institute of Innovative Research, Tokyo Institute of Technology, Yokohama, Kanagawa 226-8503, Japan.

Several species of unicellular eukaryotic algae exhibit relatively simple genomic and cellular architecture. Laboratory cultures of these algae grow faster than plants and often provide homogeneous cellular populations exposed to an almost equal environment. These characteristics are ideal for conducting experiments at the cellular and subcellular levels. Read More

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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

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Mechanism of growth amelioration of triclosan-stressed tobacco (Nicotiana tabacum) by endogenous salicylic acid.

Environ Pollut 2021 Apr 2;282:117032. Epub 2021 Apr 2.

School of Environmental Science and Engineering, Tianjin University, 92 Weijin Road, Tianjin, 300072, China.

Among emerging organic contaminants (EOCs), triclosan (TCS) is an antibacterial agent and frequently detected in sludge. In this study, RNA sequencing (RNA-seq) was used to obtain the first transcriptomic profile of tobacco with TCS treatment in comparison with control. The results of transcriptome profiling indicated that salicylic acid (SA) signalling pathway actively participated in the tobacco's response to TCS treatment. Read More

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Phytophthora infestans RXLR effector AVR1 disturbs the growth of Physcomitrium patens without affecting Sec5 localization.

PLoS One 2021 8;16(4):e0249637. Epub 2021 Apr 8.

Laboratory of Cell Biology, Wageningen University & Research, Wageningen, The Netherlands.

Plant pathogens often exploit a whole range of effectors to facilitate infection. The RXLR effector AVR1 produced by the oomycete plant pathogen Phytophthora infestans suppresses host defense by targeting Sec5. Sec5 is a subunit of the exocyst, a protein complex that is important for mediating polarized exocytosis during plant development and defense against pathogens. Read More

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Endogenous Pituitary Adenylate Cyclase-Activating Polypeptide (PACAP) Plays a Protective Effect Against Noise-Induced Hearing Loss.

Front Cell Neurosci 2021 22;15:658990. Epub 2021 Mar 22.

Institute for Neurosciences of Montpellier (INM), University Montpellier, INSERM, Montpellier, France.

Pituitary adenylyl cyclase-activating polypeptide (PACAP) is a member of the vasoactive intestinal polypeptide (VIP)-the secretin-glucagon family of neuropeptides. They act through two classes of receptors: PACAP type 1 (PAC1) and type 2 (VPAC1 and VPAC2). Among their pleiotropic effects throughout the body, PACAP functions as neuromodulators and neuroprotectors, rescuing neurons from apoptosis, mostly through the PAC1 receptor. Read More

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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

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Genome editing in fruit, ornamental, and industrial crops.

Transgenic Res 2021 Apr 6. Epub 2021 Apr 6.

Department of Horticulture, Washington State University, Pullman, WA, USA.

The advent of genome editing has opened new avenues for targeted trait enhancement in fruit, ornamental, industrial, and all specialty crops. In particular, CRISPR-based editing systems, derived from bacterial immune systems, have quickly become routinely used tools for research groups across the world seeking to edit plant genomes with a greater level of precision, higher efficiency, reduced off-target effects, and overall ease-of-use compared to ZFNs and TALENs. CRISPR systems have been applied successfully to a number of horticultural and industrial crops to enhance fruit ripening, increase stress tolerance, modify plant architecture, control the timing of flower development, and enhance the accumulation of desired metabolites, among other commercially-important traits. Read More

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In vivo proton magnetic resonance spectroscopy detection of metabolite abnormalities in aged Tat-transgenic mouse brain.

Geroscience 2021 Apr 5. Epub 2021 Apr 5.

McLean Imaging Center, McLean Hospital/Harvard Medical School, Belmont, MA, 02478, USA.

Most individuals living with HIV in the USA are over 45 years old and are vulnerable to the combined effects of HIV and aging. Antiretroviral therapies reduce HIV morbidity and mortality but do not prevent HIV trans-activator of transcription (Tat) protein expression or development of HIV-associated neurocognitive disorder (HAND), which may be caused by Tat. Tat-transgenic (Tat-tg) mice are used to study Tat's effects, typically after transgene induction with doxycycline. Read More

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Manufacturing NKG2D CAR-T cells with piggyBac transposon vectors and K562 artificial antigen-presenting cells.

Mol Ther Methods Clin Dev 2021 Jun 3;21:107-120. Epub 2021 Mar 3.

Department of Biological Sciences, National University of Singapore, Singapore 117543, Singapore.

Non-viral platforms can be applied rapidly and cost-effectively for chimeric antigen receptor (CAR)-T cell manufacturing. In the present paper, we describe in detail a clinically relevant manufacturing process for NKG2D CAR-T cells through electroporation of CAR-encoding piggyBac transposon plasmids and expansion with K562 artificial antigen-presenting cells. With an optimized protocol, we generated the final cell therapy products with 89. Read More

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Control of Microbial Opsin Expression in Stem Cell Derived Cones for Improved Outcomes in Cell Therapy.

Front Cell Neurosci 2021 18;15:648210. Epub 2021 Mar 18.

Institut de la Vision, Sorbonne Université, Paris, France.

Human-induced pluripotent stem cell (hiPSC) derived organoids have become increasingly used systems allowing 3D-modeling of human organ development, and disease. They are also a reliable source of cells for transplantation in cell therapy and an excellent model to validate gene therapies. To make full use of these systems, a toolkit of genetic modification techniques is necessary to control their activity in line with the downstream application. Read More

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Peroxiredoxin-I sustains inflammation during pancreatitis.

Cell Mol Gastroenterol Hepatol 2021 Apr 1. Epub 2021 Apr 1.

Université catholique de Louvain, de Duve Institute, Brussels, Belgium. Electronic address:

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Animal models for SARS-Cov2/Covid19 research-A commentary.

Biochem Pharmacol 2021 Apr 2;188:114543. Epub 2021 Apr 2.

Synbal, Inc., 10210 Campus Point DR. #150, San Diego, CA 92121, United States. Electronic address:

Introduction: There is an urgent need for new animal models of SARS CoV-2 infection to improve research and drug development. This brief commentary examines the deficits of current models and proposes several improved alternates. The existing single transgene mouse models poorly mimic the clinical features of COVID-19; those strains get a milder disease than human COVID-19 disease. Read More

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A Comparison of Focused and Unfocused Ultrasound for Microbubble-Mediated Gene Delivery.

Ultrasound Med Biol 2021 Mar 31. Epub 2021 Mar 31.

Department of Medicine, John A. Burns School of Medicine, Honolulu, Hawaii, USA. Electronic address:

We compared focused and unfocused ultrasound-targeted microbubble destruction (UTMD) for delivery of reporter plasmids to the liver and heart in mice. Optimal hepatic expression was seen with double-depth targeting at 5 and 13 mm in vivo, incorporating a low pulse repetition frequency and short pulse duration. Reporter expression was similar, but the transfection patterns were distinct, with intense foci of transfection using focused UTMD (F-UTMD). Read More

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BMP9 promotes methionine- and choline-deficient diet-induced nonalcoholic steatohepatitis in non-obese mice by enhancing NF-κB dependent macrophage polarization.

Int Immunopharmacol 2021 Mar 31;96:107591. Epub 2021 Mar 31.

Department of Gastroenterology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China. Electronic address:

Our previous study confirmed that bone morphogenetic protein 9 (BMP9) participated in the development of nonalcoholic steatohepatitis (NASH) by affecting macrophage polarization. The focus of this study was to further confirm the role of macrophages in BMP9-mediated NASH and to analyze the underlying mechanism. In vivo, mice that were administered adeno-associated viral (AAV) vectors containing a null transgene (AAV-null) or the BMP9 transgene (AAV-BMP9) were divided into methionine- and choline-deficient (MCD) and control diet (CD) groups, and they were administered either control liposomes or clodronate liposomes via tail vein injection, the latter to deplete macrophages. Read More

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Bacteriophage-mediated therapy of chondrosarcoma by selective delivery of the tumor necrosis factor alpha (TNFα) gene.

FASEB J 2021 May;35(5):e21487

Cancer Phage Therapy Group, Department of Brain Sciences, Faculty of Medicine, Imperial College London, London, UK.

Chondrosarcoma is a cartilage-forming bone tumor, well known for intrinsic resistance to chemotherapy and radiotherapy. We have designed a targeted chondrosarcoma gene therapy using a bacteriophage (phage) particle to deliver therapeutic genes. Phage has no tropism for mammalian cells, allowing engineered phage to be targeted to specific cell surface receptors in cancer. Read More

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Low Adenovirus Vaccine Doses Administered to Skin Using Microneedle Patches Induce Better Functional Antibody Immunogenicity as Compared to Systemic Injection.

Vaccines (Basel) 2021 Mar 22;9(3). Epub 2021 Mar 22.

School of Pharmacy, University College Cork, T12 XF62 Cork, Ireland.

Adenovirus-based vaccines are demonstrating promising clinical potential for multiple infectious diseases, including COVID-19. However, the immunogenicity of the vector itself decreases its effectiveness as a boosting vaccine due to the induction of strong anti-vector neutralizing immunity. Here we determined how dissolvable microneedle patches (DMN) for skin immunization can overcome this issue, using a clinically-relevant adenovirus-based malaria vaccine, AdHu5-PfRH5, in mice. Read More

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Delivery Systems for Nucleic Acids and Proteins: Barriers, Cell Capture Pathways and Nanocarriers.

Pharmaceutics 2021 Mar 22;13(3). Epub 2021 Mar 22.

Grupo de Diseño de Productos y Procesos (GDPP), Department of Chemical and Food Engineering, Universidad de los Andes, Bogotá 111711, Colombia.

Gene therapy has been used as a potential approach to address the diagnosis and treatment of genetic diseases and inherited disorders. In this line, non-viral systems have been exploited as promising alternatives for delivering therapeutic transgenes and proteins. In this review, we explored how biological barriers are effectively overcome by non-viral systems, usually nanoparticles, to reach an efficient delivery of cargoes. Read More

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Myxoma Virus Expressing LIGHT (TNFSF14) Pre-Loaded into Adipose-Derived Mesenchymal Stem Cells Is Effective Treatment for Murine Pancreatic Adenocarcinoma.

Cancers (Basel) 2021 Mar 19;13(6). Epub 2021 Mar 19.

Center for Translational Research and Molecular Biology of Cancer, Maria Sklodowska-Curie National Research Institute of Oncology, Gliwice Branch, Wybrzeze AK 15, 44-102 Gliwice, Poland.

Pancreatic ductal adenocarcinoma (PDAC) is a weakly immunogenic fatal neoplasm. Oncolytic viruses with dual anti-cancer properties-oncolytic and immune response-boosting effects-have great potential for PDAC management. Adipose-derived stem cells (ADSCs) of mesenchymal origin were infected ex vivo with recombinant myxoma virus (MYXV), which encodes murine LIGHT, also called tumor necrosis factor ligand superfamily member 14 (TNFSF14). Read More

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