A5009654306- Virus-based gene therapy research
- Carcinogens and Genotoxicity Assessment
- Animal testing and alternatives
- CRISPR and Genetic Engineering
- Trace Elements in Health
- Cardiac electrophysiology and arrhythmias
- Immunotoxicology and immune responses
- CAR-T cell therapy research
- Neuroscience and Neuropharmacology Research
- Acute Kidney Injury Research
- Atherosclerosis and Cardiovascular Diseases
- Renin-Angiotensin System Studies
- Nitric Oxide and Endothelin Effects
- Amino Acid Enzymes and Metabolism
- Cancer Research and Treatments
- Renal and related cancers
- Lysosomal Storage Disorders Research
- Lipid Membrane Structure and Behavior
- Heavy Metal Exposure and Toxicity
- Computational Drug Discovery Methods
- Metabolism and Genetic Disorders
- Peroxisome Proliferator-Activated Receptors
- Blood Pressure and Hypertension Studies
- Cancer, Stress, Anesthesia, and Immune Response
- Organometallic Compounds Synthesis and Characterization
Istituti di Ricovero e Cura a Carattere Scientifico
2018-2025
The San Raffaele Telethon Institute for Gene Therapy
2016-2025
GlaxoSmithKline (Italy)
2002-2024
Telethon Foundation
2023-2024
GlaxoSmithKline (United Kingdom)
2011-2020
Age UK
2020
Istituto di Ricovero e Cura a Carattere Scientifico San Raffaele
2018-2020
University of Padua
2008
University of Verona
1992-2003
University of Ferrara
1987
Lentiviral vectors with high surface content of CD47 improved gene transfer efficiency to hepatocytes in nonhuman primates.
Despite recent progress in cancer treatment, liver metastases persist as an unmet clinical need. Here, we show that arming and tumor-associated macrophages vivo to co-express tumor antigens (TAs), IFNα, IL-12 unleashes robust anti-tumor immune responses, leading the regression of metastases. Mechanistically, armed expand reactive CD8+ T cells, which acquire features progenitor exhausted cells kill independently CD4+ cell help. IFNα produced by reprogram antigen presenting rewire cellular...
Gold(III)-dithiocarbamato complexes have recently gained increasing attention as potential anticancer agents because of their strong tumor cell growth--inhibitory effects, generally achieved by exploiting non-cisplatin-like mechanisms action. The rationale our research work is to combine the antitumor properties gold(III) metal center with chemoprotective function coordinated dithiocarbamates in order reduce toxic side effects (in particular nephrotoxicity) induced clinically established...
Dose-response expression of kidney injury molecule-1 (KIM-1) gene in cortex and its correlation with morphology traditional biomarkers nephrotoxicity (plasma creatinine blood urea nitrogen, BUN) or segment-specific marker proximal tubule (kidney glutamine synthetase, GSK) were studied male rats treated nephrotoxicants. These included hexachloro-1:3-butadiene (HCBD, S(3) segment-specific), potassium dichromate (chromate, S(1)-S(2) cephaloridine (Cph, S(2) segment-specific). Rats a single...
The correspondence between histopathological findings and segment-specific biomarkers was investigated in rats treated with nephrotoxicants. Male Wistar were a single injection of K 2 Cr O 7 (25 mg/kg sc saline), cis-Pt (10 ip buffered MSO) or HCBD (100 corn oil). Twenty-four 48 hours after treatment, the sacrificed kidneys drawn for biochemical evaluation, i.e., GS activity renal cortex PAH uptake cortical slices. Histopathological show that cause diffuse necrosis S 3 segment proximal...
In order to support the clinical application of hematopoietic stem cell (HSC) gene therapy for mucopolysaccharidosis I (MPS I), biosafety studies were conducted assess toxicity and tumorigenic potential, as well biodistribution HSCs progenitor cells (HSPCs) transduced with lentiviral vectors (LV) encoding cDNA alpha-iduronidase (IDUA) gene, which is mutated in MPS patients. To this goal, toxicology conducted, employing Good Laboratory Practice principles. Vector integration site (IS) applied...
Cardiovascular safety signals in nonclinical studies remain among the main reasons for drug attrition during pharmaceutical research and development. Drug-induced changes can be functional and/or associated with morphological alterations normal heart histology. It is therefore crucial to understand variations histology discriminate test article-related from background lesions. Rodent progressive cardiomyopathy probably most commonly encountered change control animals of toxicity studies. A...
Chronic granulomatous disease (CGD) is a rare inherited disorder due to loss-of-function mutations in genes encoding the NADPH oxidase subunits. Hematopoietic stem and progenitor cell (HSPC) gene therapy (GT) using regulated lentiviral vectors (LVs) has emerged as promising therapeutic option for CGD patients. We performed non-clinical Good Laboratory Practice (GLP) laboratory-grade studies assess safety genotoxicity of LV targeting myeloid-specific Gp91phox expression X-linked chronic...
Background: Serum protein analysis in both humans and experimental animal species has so far been carried out by labor‐intensive techniques, such as agarose gel electrophoresis (AGE). Objective: The objective of this study was to evaluate capillary (CE) an alternative technique AGE for the serum proteins from healthy animals. Methods: Blood samples were collected into tubes without anticoagulant 6 fasted male mice, rats, dogs, marmosets, humans. separated CE using a standardized human...
Cardiovascular toxicity represents one of the major reasons for termination development drugs, even in late phases. This growing issue is often not restricted to specific therapeutic areas, and it gaining critical importance, particular chronically administered highlighting limitations terms sensitivity current investigational paradigms. Furthermore, drug-related changes may become evident after long-term administration different reasons, including accumulation drug heart. article describes...
Gene therapy clinical trials require rigorous non-clinical studies in the most relevant models to assess benefit-to-risk ratio. To support development of gene for β-thalassemia, we performed vitro and vivo prediction safety. First developed newly GLOBE-derived vectors that were tested their transcriptional activity potential interference with expression surrounding genes. Because these did not show significant advantages, GLOBE lentiviral vector (LV) was elected further safety...
Background Lacidipine is a widely used calcium-channel blocker, which has both long-lasting antihypertensive activity and also antioxidant properties. Previous studies have demonstrated the ability of lacidipine to reduce development atherosclerotic lesions in several animal models. Objective The present study investigated anti-atherosclerotic potential apoE-deficient mouse, an experimental model atherosclerosis showing progressively complex widespread closely resemble inflammatory-fibrous...
In dogs Helicobacter spp. are found in all gastric regions usually localized the surface mucus, glands and parietal cells. The aim of this study was to detail distribution fundic mucosa asymptomatic Beagle their intracellular localization within cells, order evaluate species-specific pathogenetic effects on presence investigated by immunohistochemistry, TEM, PCR six dogs. were examined, H. bizzozeronii felis identified confirmed TEM. lumen glands, co-localization common. present larger...