Search Our Scientific Publications & Authors

J Vis Exp 2021 Mar 31(169). Epub 2021 Mar 31.

LBMC, Laboratoire de Biologie et Modélisation de la Cellule Univ Lyon, ENS de Lyon, Université Claude Bernard Lyon 1, CNRS, UMR 5239, INSERM, U1210, Lyon, 69007, France;

The clustered regularly interspaced short palindromic repeats (CRISPR)-Cas system has democratized genome-editing in eukaryotic cells and led to the development of numerous innovative applications. However, delivery of the Cas9 protein and single-guide RNA (sgRNA) into target cells can be technically challenge. Classical viral vectors, such as those derived from lentiviruses (LVs) or adeno-associated viruses (AAVs), allow for efficient delivery of transgenes coding for the Cas9 protein and its associated sgRNA in many primary cells and in vivo. Read More

Mol Ther Methods Clin Dev 2021 Jun 29;21:399-412. Epub 2021 Mar 29.

Department of Neuroscience and Rehabilitation, Section of Pharmacology, University of Ferrara, 44121 Ferrara, Italy.

A key factor for developing gene therapy strategies for neurological disorders is the availability of suitable vectors. Currently, the most advanced are adeno-associated vectors that, while being safe and ensuring long-lasting transgene expression, have a very limited cargo capacity. In contrast, herpes simplex virus-based amplicon vectors can host huge amounts of foreign DNA, but concerns exist about their safety and ability to express transgenes long-term. Read More

Front Oncol 2021 18;11:609918. Epub 2021 Mar 18.

Division of Basic Biomedical Sciences, Sanford School of Medicine, University of South Dakota, Vermillion, SD, United States.

Breast tumors contain both transformed epithelial cells and non-transformed stroma cells producing secreted factors that can promote metastasis. Previously, we demonstrated that the kinase MEKK1 regulates cell migration and gene expression, and that transgene-induced breast tumor metastasis is markedly inhibited in MEKK1-deficient mice. In this report, we examined the role of MEKK1 in stroma cell gene expression and the consequent effect on breast tumor cell function. Read More

Front Plant Sci 2021 1;12:650215. Epub 2021 Apr 1.

Department of Horticulture, Michigan State University, East Lansing, MI, United States.

Abiotic stresses, mainly salinity and drought, are the most important environmental threats that constrain worldwide food security by hampering plant growth and productivity. Plants cope with the adverse effects of these stresses by implementing a series of morpho-physio-biochemical adaptation mechanisms. Accumulating effective osmo-protectants, such as proline and glycine betaine (GB), is one of the important plant stress tolerance strategies. Read More

Rev Neurosci 2021 Apr 16. Epub 2021 Apr 16.

Institute of Human Genetics, Faculty of Medicine and University Hospital Cologne, University of Cologne, Kerpener Str. 34, 50931Cologne, Germany.

The microtubule-associated protein (MAP) TAU is mainly sorted into the axon of healthy brain neurons. Somatodendritic missorting of TAU is a pathological hallmark of many neurodegenerative diseases, including Alzheimer's disease (AD). Cause, consequence and (patho)physiological mechanisms of TAU sorting and missorting are understudied, in part also because of the lack of readily available human neuronal model systems. Read More

Hum Gene Ther 2021 Apr 16. Epub 2021 Apr 16.

Emory University, 1371, Yerkes National Primate Research Center, Atlanta, Georgia, United States.

Viral vectors made from adeno-associated virus (AAV) have emerged as preferred tools in basic and translational neuroscience research to introduce or modify genetic material in cells of interest. The use of viral vectors is particularly attractive in non-transgenic species, such as non-human primates. Injections of AAV solutions into the cerebrospinal fluid (CSF) is an effective method to achieve a broad distribution of a transgene in the central nervous system. Read More

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

Polymers (Basel) 2021 Mar 5;13(5). Epub 2021 Mar 5.

CICS-UBI-Health Sciences Research Centre, Universidade da Beira Interior, Avenida Infante D. Henrique, 6200-506 Covilhã, Portugal.

Gene therapy could be simply defined as a strategy for the introduction of a functional copy of desired genes in patients, to correct some specific mutation and potentially treat the respective disorder. However, this straightforward definition hides very complex processes related to the design and preparation of the therapeutic genes, as well as the development of suitable gene delivery systems. Within non-viral vectors, polymeric nanocarriers have offered an ideal platform to be applied as gene delivery systems. Read More

Plants (Basel) 2021 Mar 29;10(4). Epub 2021 Mar 29.

Departamento de Biotecnología Microbiana y de Plantas, Centro de Investigaciones Biológicas Margarita Salas, CSIC, 28040 Madrid, Spain.

Exogenous application of double-stranded RNAs (dsRNAs) for inducing virus resistance in plants represents an attractive alternative to transgene-based silencing approaches. However, improvement of dsRNA stability in natural conditions is required in order to provide long-term protection against the targeted virus. Here, we tested the protective effect of topical application of -encapsulated dsRNA compared to naked dsRNA against single and dual infection by expressing the green fluorescent protein (PVX-GFP) and Potato virus Y (PVY) in . Read More

Plants (Basel) 2021 Mar 24;10(4). Epub 2021 Mar 24.

International Institute of Tropical Agriculture, Biosciences, P.O. Box 30709, Nairobi 00100, Kenya.

The banana aphid, , is the sole insect vector of banana bunchy top virus (BBTV), the causal agent of banana bunchy top disease. The aphid acquires and transmits BBTV while feeding on infected banana plants. RNA interference (RNAi) enables the generation of pest and disease-resistant crops; however, its effectiveness relies on the identification of pivotal gene sequences to target and silence. Read More

Int J Mol Sci 2021 Mar 24;22(7). Epub 2021 Mar 24.

Department of Genomics and Postgenomic Technologies, Gene Immunooncotherapy Group, Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry RAS, 117997 Moscow, Russia.

Cancer-associated fibroblasts (CAF) are attractive therapeutic targets in the tumor microenvironment. The possibility of using CAFs as a source of therapeutic molecules is a challenging approach in gene therapy. This requires transcriptional targeting of transgene expression by cis-regulatory elements (CRE). Read More