A5014283915- Virus-based gene therapy research
- Viral Infectious Diseases and Gene Expression in Insects
- CAR-T cell therapy research
- RNA Interference and Gene Delivery
- Immunotherapy and Immune Responses
- Cancer Immunotherapy and Biomarkers
- Epilepsy research and treatment
- CRISPR and Genetic Engineering
- Immune Cell Function and Interaction
- interferon and immune responses
- Neuroscience and Neuropharmacology Research
- RNA regulation and disease
- Endoplasmic Reticulum Stress and Disease
- Immune cells in cancer
- Drug Transport and Resistance Mechanisms
- Ubiquitin and proteasome pathways
- Cytokine Signaling Pathways and Interactions
- Cholesterol and Lipid Metabolism
- Hepatitis B Virus Studies
- Zebrafish Biomedical Research Applications
- Porphyrin Metabolism and Disorders
- Neutrophil, Myeloperoxidase and Oxidative Mechanisms
- Heme Oxygenase-1 and Carbon Monoxide
- Hormonal Regulation and Hypertension
- Genetics and Neurodevelopmental Disorders
Universidad de Navarra
2013-2024
Navarre Institute of Health Research
2017-2021
New options are needed for the management and prevention of colorectal cancer liver metastases. Interleukin 12 (IL-12) is an immunostimulatory cytokine with proven antitumour effect in animal models. Despite evidence indicating its biological humans, neither recombinant protein nor gene therapy vectors expressing IL-12 have shown a relevant benefit patients cancer.To develop new approach to overcome difficulties obtaining suitable expression pattern immunosuppressive milieu tumours which...
Abstract Dravet Syndrome (DS) is an encephalopathy with epilepsy associated multiple neuropsychiatric comorbidities. In up to 90% of cases, it caused by functional happloinsufficiency the SCN1A gene, which encodes alpha subunit a voltage-dependent sodium channel (Nav1.1). Preclinical development new targeted therapies requires accessible animal models recapitulate disease at genetic and clinical levels. Here we describe that C57BL/6 J knock-in mouse strain carrying heterozygous, clinically...
IL-8 (CXCL-8) is a chemoattractant factor for myeloid leukocytes, that produced in large quantities by many solid tumors. Levels of IL-8, which can act upon variety immune and nonimmune cells, tell us lot about tumors, including their size (positive association) how likely they are to respond immunotherapy (negative association). This because the tumors promote angiogenesis, recruit immunosuppressive cells like neutrophils myeloid-derived suppressor (MDSCs), stimulate...
Dravet syndrome is a genetic encephalopathy characterized by severe epilepsy combined with motor, cognitive, and behavioral abnormalities. Current antiepileptic drugs achieve only partial control of seizures provide little benefit on the patient's neurological development. In >80% cases, disease caused haploinsufficiency SCN1A gene, which encodes alpha subunit Nav1.1 voltage-gated sodium channel. Novel therapies aim to restore expression in order address all manifestations. We evidence that...
Abstract Background Bioluminescent imaging (BLI) is based on the detection of light emitted by living cells expressing a luciferase gene. Stable transfection in cancer and their inoculation into permissive animals allows noninvasive monitorization tumor progression inside internal organs. We have applied this technology for development murine model colorectal involving liver, with aim improving pre-clinical evaluation new anticancer therapies. Results A colon cell line stably transfected...
Regulatory T cells (Treg) play a critical role in the modulation of immune responses to viral antigens chronic hepatitis. Woodchucks (Marmota monax) infected with woodchuck hepatitis virus (WHV) represent best animal model for B (HBV) infection. Examination intrahepatic and peripheral Treg uninfected WHV chronically woodchucks showed significant increase numbers animals, whereas no differences were found blood. In agreement these data, higher expression levels Forkhead box P3 (Foxp3),...
Acute intermittent porphyria (AIP) is a hepatic metabolic disease that results from haplo-insufficient activity of porphobilinogen deaminase (PBGD). The dominant clinical feature acute attacks when heme synthesis activated by endocrine or exogenous factors. Gene therapy vectors over-expressing PBGD protein in the liver offers potential as cure for AIP. Here, we developed helper-dependent adenovirus (HDA) encoding human (hPBGD) and assessed its therapeutic efficacy murine model Intravenous...
The limited efficacy of current treatments against pancreatic cancer has prompted the search new alternatives such as virotherapy. Activation immune response cells is emerging one main mechanisms action oncolytic viruses (OV). Direct oncolysis releases tumor antigens, and viral replication within microenvironment a potent danger signal. Arming OV with immunostimulatory transgenes further enhances their therapeutic effect. However, standard virotherapy protocols do not take full advantage...
Abstract The SCN1A gene encodes the alpha subunit of a voltage-gated sodium channel (Na v 1.1), which is essential for function inhibitory neurons in brain. Mutations this cause severe encephalopathies such as Dravet syndrome (DS). Upregulation expression by different approaches has demonstrated promising therapeutic effects preclinical models DS. Limiting effect to may contribute restoration brain homeostasis, increasing safety and efficacy treatment. In work, we have evaluated obtain...
Different screening methods are being developed to generate adeno-associated viral vectors (AAV) with the ability bypass blood-brain barrier (BBB) upon intravenous administration. Recently, AAV9P31 stood out as most efficient version among a library of peptide-displaying capsids selected in C57BL/6 mice using RNA-driven biopanning. In this work we have characterized detail its biodistribution different mouse strains (C57BL/6 and Balb/c), well Sprague Dawley rats non-human primates (Macaca...
Cerebrotendinous xanthomatosis (CTX) is an autosomal recessive disease caused by mutations in the CYP27A1 gene, encoding sterol 27-hydroxylase. Disruption of bile acid biosynthesis pathway and accumulation toxic precursors such as cholestanol cause chronic diarrhea, bilateral juvenile cataracts, tissue deposition cholesterol (xanthomas), progressive motor/neuropsychiatric alterations. We have evaluated therapeutic potential adeno-associated virus (AAV) vectors expressing a CTX mouse model....
Viral vector use is wide-spread in the field of gene therapy, with new clinical trials starting every year for different human pathologies and a growing number agents being approved by regulatory agencies. However, preclinical testing long expensive, especially during early stages development. Nowadays, model organism par excellence mouse (Mus musculus), there are few investigations which alternative models used. Here, we assess possibility using zebrafish (Danio rerio) as an vivo adenoviral...
Immune checkpoint inhibitors (ICIs) have demonstrated remarkable efficacy in a growing number of malignancies. However, overcoming primary or secondary resistances is difficult due to pharmacokinetics issues and side effects associated with high systemic exposure. Local regional expression monoclonal antibodies (mAbs) using gene therapy vectors can alleviate this problem. In work, we describe high-capacity adenoviral vector (HCA-EFZP-aPDL1) equipped mifepristone-inducible system for the...
Osteosarcoma is the most frequent and aggressive bone tumor in children adolescents, with a long-term survival rate of 30%. Interleukin-12 (IL-12) potent cytokine that bridges innate adaptive immunity, triggers antiangiogenic responses, achieves antitumor effects. In this work, we evaluated antisarcoma effect high-capacity adenoviral vector encoding mouse IL-12. This harbored mifepristone-inducible system for controlled expression IL-12 (High-Capacity enconding EF1α promoter...
Several dinucleotide cyclases, including cyclic GMP-AMP synthase, and their involvement in STING-mediated immunity have been extensively studied. In this study, we tested five bacterial diguanylate cyclases from the Gram-negative bacterium Salmonella Enteritidis, identifying AdrA as most potent inducer of a IFN response. wild-type (wt) or its inactive version mutant (mut) were delivered by an adenovirus (Ad) vector. Dendritic cells obtained wt mice infected vitro with Ad vector containing...
Cytokines are small proteins that crucial for controlling the growth and activity of blood cells other immune system [...]
High-capacity adenoviral vectors (HC-AdV) show extended DNA payload and stability of gene expression in vivo due to the absence viral coding sequences. However, production requires methods trans-complement proteins, usually through Helper Viruses (HV). The Cre/loxP system is frequently employed remove packaging signal HV genomes, order avoid their encapsidation. chronic exposure Cre recombinase cells detrimental. We have applied dimerizable overcome this limitation.Cre was split two...
<title>Abstract</title> Different screening methods are being developed to generate adeno-associated viral vectors (AAV) with the ability bypass blood-brain barrier (BBB) upon intravenous administration. Recently, AAV9P31 stood out as most efficient version among a library of peptide-displaying capsids selected in C57BL/6 mice using RNA-driven biopanning. In this work we have characterized detail its biodistribution different mouse strains (C57BL/6 and Balb/c), well Sprague Dawley rats...