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Noninvasive Prenatal Diagnosis of Trisomy 21 via droplets-based Circulating Fetal Cells Genetic Analysis. – KaryoDrop
Trisomy 21 is the most common chromosomal aberration that causes a birth defect widely known as Down Syndrome. Improvements in technology have allowed development of increasingly sensitive non-invasive tests to calculate the risk of trisomy 21. However, these tests can be prohibitively expensive and
PURImaging – Development of radiotracers targeting PURInoreceptor P2Y12, a promising target for positron emission tomography (PET) imaging of neuro-inflammation – PURImaging
Neurodegenerative and neurological disorders induce a neuroinflammatory response within the central nervous system (CNS) in order to limit the extent of the disease and to support repair and regeneration. However, various disease mechanisms may lead to harmful chronic neuro-inflammation contributing
Dissecting the transcriptional and epigenetic regulation of HEMOglobin to unravel novel CURativE options for beta-hemoglobinopathies – HEMOCURE
Beta-hemoglobinopathies are caused by mutations affecting the production of the adult hemoglobin beta-chain. Persistence of fetal gamma-globin chain synthesis in adult life substantially ameliorates the clinical phenotype of beta-hemoglobinopathy patients. Currently, allogenic hematopoietic stem c
Prevention and gene therapy of viral encephalitis using specific interferon-stimulated genes – ISG-therapy
Novel strategies are required to fight viruses that invade the brain. Viral infections elicit an innate immune response mediated by type I interferons (IFNs), in turn inducing hundreds of IFN-stimulated genes (ISGs). Despite their broad antiviral efficacy, IFN usage is limited in the clinic because
Dual Labelling of low density Lipoproteins to Image and Characterize Atherosclerosis and cell Types with Elevated LDL uptake – DLLICATE
Atherosclerosis is a leading cause of death worldwide. This complex disease is the subject of intensive research to improve detection/diagnosis and consequently therapeutic approaches. The exploration of atherosclerotic disease requires different imaging techniques such as echography, X rays, magnet
Evaluating in vivo the antitumoral efficacy of an antibody drug conjugate agaisnt FSHR – FSHRcancer
The follicle-stimulating hormone receptor (FSHR) is expressed selectively on the luminal surface of tumor blood vessels located at the periphery of the tumors. Disruption of FSHR+ blood vessels may provide a new strategy in cancer therapy. The objective of this project is to obtain preclinical proof
Development of a 3D in vitro model to mimic the osseo- and soft tissue-integration process of dental implants – IDEAL-3D
The aim of this project is to fabricate and evaluate an in vitro 3D model representative of the processes of osseointegration and soft tissue integration of dental implants, using Bioprinting techniques, in order to serve as a reliable and reproducible platform for research in implant dentistry. In
Bioproduction of therapeutic extracellular vesicles from insulin cells – Bioprod-sEVforT1D
Type 1 diabetes (T1D) is a chronic disease caused by the auto-immune destruction of pancreatic beta cells. Small extracellular vesicles (sEV) released by healthy beta cells are promising candidates for T1D therapy thanks to their aptitude to reprogram the autoreactif immune system towards tolerance,
A matrix therapy to optimize MSC-derived extracellular vesicles for brain protection and repair after ischemia – MAESTROVE
Regenerative therapy based on the use of mesenchymal stem cells (MSC) is a promising approach for the treatment of stroke. The beneficial effects of MSC appears to be mainly related to the secretion of cellular factors and/or extracellular vesicles (EV). Heparan sulfates present on the surface of pr
Roscovitine analogues as targeted pharmacotherapies for rare cholestatic liver diseases – RAPRACLID
Bile secretion is an essential function of the liver necessary for fat digestion as well as elimination of xenobiotics and endogenous metabolites. This function mainly depends on ATP-Binding Cassette (ABC) transporters located at the canalicular membrane of hepatocytes and responsible for the secret
Non-invasive gene therapy for Parkinson disease: Improve delivery of AAV vectors by single Intravenous delivery combined with Focused UltraSound (FUS). – FAB
Recent results demonstrated that gene therapy is an efficient strategy to treat rare or complex diseases of the central nervous system (CNS). Delivering therapeutic genes to the CNS mostly relies on Adeno-Associated Viruses (AAVs) vectors that can efficiently, safely and stably transduce neurons fol
Development and biological characterization of dual-targeting inhibitors against the apicomplexan parasite Plasmodium falciparum – DualTargApi
.Plasmodium falciparum, a protozoan pathogen, is still the greatest threat causing malaria with severe clinical significance and negative socio economic impact. This parasite possesses a substantial repertoire of conserved enzymes including those involved in chromatin remodeling and histone modifica
Molecular Activations by Ionizing Radiation for Theranostic Approaches – MAIRTA
The development of tools establishing both a diagnostic and adapted therapeutic actions with control in space and time, is crucial in the emerging field of personalized medicine. Several sophisticated photoactivable systems, able to induce specific molecular actions, have been proposed in the last f
Development of Succinate-based analogues and formulations against SARS-CoV-2 and influenza viruses-induced respiratory infections – SuccesS
The emergence of pandemic respiratory viruses is a major concern. Those viruses include coronaviruses such as SARS-CoV-2 and influenza A viruses (IAV). There are currently no efficient drugs against coronaviruses and the efficacy of anti-IAV drugs is disputed. Vaccination should constitute the most
Development of microfluidic devices to model Heart-Brain interactions in Torsades de Pointes – NeuroCard
Torsades de Pointes (TdPs) are malignant ventricular arrhythmia leading to sudden death. TdPs are observed in active patients without any structural cardiac defect, thus emphasizing the need of an early detection of “at-risk” patients. TdP is manifested by an abnormal lengthening of the ventricular
Purine Analogues as anti-Malarial Drug – PAMalaD
Malaria, which remains one of the deadliest infectious diseases, is caused by a parasite of the genus Plasmodium and is spread by the bite of Anopheles mosquitoes. The emergence of parasites resistant to all current antimalarial drugs including artemisinin-based combination therapies (ACTs) highligh
Pulmonary administration of antibiotic nano-emulsion to treat gram-negative bacteria infections – PAANIC
Multiple drug resistance (MDR) bacteria that cause pneumonia, such as P. aeruginosa, A. baumannii, and K. pneumoniae are extremely difficult to treat, and resistances to last-resort antibiotics (ATB) such as colistin are increasingly reported. We have lately observed that some terpenes reinforce the
Circulating IMMune cell recruitment in Skin – CIMMS
The main function of the skin is to constitute a barrier against external aggressions. Protective mechanisms in the skin depend in part on the presence of tissue-resident immune cells and the recruitment of circulating immune cells from the blood. Genoskin has developed two ex vivo human skin models
Innovative strategy for the selective inhibition of the pathological effects of a multifunctional therapeutic target: the case of USP8 – DruggingUSP8
The DruggingUSP8 project is led by a consortium of four academic and private partners, with complementary expertise in molecular and cellular biology, structural biology, clinical and drug discovery. It aims to specifically inhibit the pathological effects of a multifunctional enzyme, the ubiquitin
Monitoring ß cell energy state: a new FRET toolkit – betaFRET
Genetically encoded sensors based on Fluorescence Resonance Energy Transfer (FRET) hold the promise of being game-changers in our understanding of intracellular physiology. We have developed and tested AMPfret, the first nano-sensor capable of faithfully reporting energy states in vivo by measuring
Tau seeds in extracellular vesicles which proteforms? – TAUSEED
The initial clinical presentations of Alzheimer's disease (AD), progressive supranuclear palsy (PSP, parkinsonism) and Pick's disease (PiD, a subgroup of frontotemporal lobar degeneration) are sometimes similar: primary progressive aphasia, behavioural disorders, etc. Early diagnosis is therefore di
First pre-clinical validation of fluorinated ligands for the 18F TEP diagnosis of synucleinopathies – Syn4Diag
Positron emission tomography (PET) is a unique tool for the in vivo exploration of neurodegenerative diseases characterized by the aberrant deposition of specific protein species. The aim of SYN4DIAG is to develop a PET tracer of aggregated alpha-synuclein (a-syn), as such a probe does not yet exist
SPAtio-temporal control of CEllular differentiation for CARtilage Tissue engineering – Spacecart
The combination of Bone Marrow Mesenchymal Stromal Cells (BM-MSC) with active injectable carriers brings about innovative solutions to current issues in the field of tissue engineering. In particular, repair of adult articular cartilage lesions remains a clinical challenge because of the limited sel
Synergistic action of a photosensitizer and antimicrobial peptides for superbugs destruction – SAFEST
The fast spread of multi-resistant microorganisms represents a threat to public health that urgently needs new therapeutic approaches less prone to the development of resistant strains. Our objectives are the design, synthesis and in-depth biophysical studies of new antimicrobial peptide-photosensit
Rescue of Nav1.2 Sodium Channel Functions in Severe Neurodevelopmental Disorders – Nav12RESCUE
Mutations that reduce Nav1.2/SCN2A sodium channel function are major players in a large spectrum of severe untreatable neurodevelopmental disorders, but specific pathological mechanisms are not clear yet. Importantly, there are no treatments available that can target Nav1.2 loss of function. Our pre
Developing fungal bromodomain inhibitors as a potential new class of antifungal drugs – FungiBD
Invasive fungal infections cause over 1.5 million deaths annually worldwide. The limited repertoire of available drugs and a rise in drug-resistant strains has led to an urgent need for novel therapeutic strategies. In this project we propose to target chromatin signaling pathways mediated by bromod
Targeting A2A receptor in autism: single domain antibodies for direct inhibition or antagonist vectorization – A2utismAb
Among adenosine receptors, the A2A receptor (A2AR) is a G-protein coupled receptor (GPCR) that receives raising attention as a therapeutic target in multiple pathologies. Brain A2AR expression is quasi exclusively striatal, and A2AR anatgonists, as istradefylline, inhibit the activity of striatal ne
Design of a versatile in silico fragment-based drug design tool – UniversalF2D
Fragment-Based Drug Design (FBDD) is an approach widely developed and used in academic laboratories and pharmaceutical companies for the past twenty years. Nowadays, several drugs approved by the FDA or advanced in clinical trials were discovered from FBDD. To go further and gain in time and efficie
Preclinical evaluation, in a big animal model, of a tissue-engineered vascular substitute derived from the human umbilical cord – smiling
Cardiovascular disease (CVD) accounts for nearly one-third of all deaths worldwide. Coronary heart disease, obstructive arterial disease of the lower limbs and cerebrovascular disease are the main causes. Among the treatments proposed, vascular bypass surgery remains the most effective treatment for
Modified Bacteria for Mn-based anti-oxidants production and Delivery for gut Inflammation Control – MOBIDIC
The objective of the MOBIDIC project is to develop an innovative approach to the treatment of inflammatory bowel diseases (IBD) using new oral bio-medicines. To date, these diseases remain incurable. As one of the first triggers of inflammation is an overproduction of reactive oxygen species, we pro
Rapid and low-cost diagnostics of sickle-cell disease using the coffee-ring effect – SCDiag
Sickle cell disease (SCD), a highly frequent and widely spread genetic disease, is a strongly disabling to lethal blood pathology due to pathogenic hemoglobin mutations. Its impact on public health is dramatic, particularly in developing countries where current testing technologies are too costly to
Role of Dact3 in the intestinal homeostasis: Elucidating the mechanism of Action of the anti-inflammatory Commensal bacTerium Faecalibacterium prausnitzii (REACT) – REACT
Inflammatory bowel diseases (IBD) are chronic inflammatory disorders of the gut with a substantial socioeconomic and health impact worldwide. Unfortunately, there is no cure for IBD and present therapies are only attenuating the inflammatory response. A promising approach to prevent and treat IBD in
Immunomodulatory properties of Smac mimetic on the primary tumor and after tumor resection on preclinical mouse and human models in glioblastoma – MEGA01
The establishment of an immunocompetent microenvironment represents a major therapeutic challenge in the treatment of glioblastoma. These brain tumors are one of the most angiogenic and immunosuppressive tumors with limited therapeutic options. To increase treatment efficiency, we need molecules tar
Novel compounds for the treatment of chronic kidney disease – treatCKD
Around 850 million people were estimated to have CKD in 2017, representing ~11% the world population. The treatCKD project aims to accumulate preclinical evidence for two novel and innovative candidate compounds for the treatment of CKD. The compounds answer an unmet medical need by either focusing
Endogenous retroviruses and their receptors: development of new targeted virotherapy tools – EndoRetroTarget
Elements of retroviral origin, or HERVs (human endogenous retroviruses), represent a significant proportion of the human genome. Globally repressed because of their infectious origin, they can be expressed in normal contexts, notably placentation, and/or pathological contexts. In cancer, epigenetic
AntiMicrobial Agents from LIchen Associated bacteria – AMALIA
Antibiotic resistance (AR) and persistence of pathogenic microorganisms are emerging threats to human health, as the number of antibiotics effective against resistant bacteria is increasingly scarce. Microbe-host symbiotic interactions often depend on bioactive molecules with an antibiotic potential
All-in-one 3D cell-based hollow liver capsules for drug screening assays: a comprehensive engineering, functional and molecular investigation – REVIL
Hepatotoxicity testing is a key challenge in drug validation. There is an urgent need for the design and development of reliable vitro human hepatic models that may be eligible for the safety evaluation of chemical compounds. While primary hepatocytes (PHHs) remain the gold standard, the long-term m
Controlable RNA expressing Scaffold for Bone Regeneration – CreaBone
The need for bone repair is exponentially rising due to increases in life expectancy and accidents. Natural bone grafts either autografts or allografts (from cadavers) are traditionally used as replacements. Yet, they present limited availability, morbidity of donor and acceptor sites and variabilit
Tendon organoid for drug screening – TENORS
Chronic tendon injury or tendinopathy is a major health issue. Causes of tendinopathies are multiple and include, excess load, intense training, metabolic disorders, ageing and drugs. Drug-induced tendon disorders are often underestimated and pointed out only when the molecule has been authorized fo
Degradable synthetic antibacterial copolymers for therapeutic applications – COPOTIC
Bacterial resistance to antibiotics has become a major public health issue. Indeed, mainly because of the overconsumption and/or misuse of antibiotics, many strains of bacteria have become resistant or even multi-resistant to current antibiotics. Moreover, very few new antibiotics are proposed eac
Pre-clinical development of natural compound-based drugs, targeting IL-23-Th17 pathway in immune-mediated inflammatory diseases – IMIDRUG
We are developing a new class of antiinflammatory drugs dedicated to immune-mediated inflammatory diseases (IMID) a heterogeneous group of diseases characterized by acute or chronic inflammation affecting any organ system whose physiopathology includes imbalance of inflammatory cytokines. IMID cause
Selection and adaptation of siRNA vectors by live cells – SACSI
The SACSI project will study the self-assembly of unprecedented pH-responsive – undergoing conformational changes upon cell uptake that promote endosomal escape siRNA release in the cytoplasm – amphiphilic dynamic covalent polymers for generating targeted nano-vectors of siRNA capable of adaptation
Role of Corticoids in Ocular Rosacea – ROCOR
Due to the limited understanding of disease mechanisms and the lack of specific diagnostic tests, OR is underdiagnosed. Yet, it is estimated that 10 to 50% of patients with skin rosacea (representing 10% of the general adult population) have ocular involvement. The current therapeutic options offer
Development of kallikrein-related peptidase 6 inhibitors to treat multiple sclerosis – RESTORE
Multiple sclerosis (MS) is the most common neurological disorder and the leading cause of non-traumatic disability in young adults. MS affects 2.5 million people worldwide, including more than 100,000 in France. It is associated with an inflammatory reaction of the central nervous system (CNS) that
Targeting host-parasite interactions through the inhibition of excreted Leishmania casein kinase 1 – TEXLEISH
Leishmaniasis is a severe public health issue and the current treatments are toxic, costly or lead to parasite resistance, thus there is an urgent need for new drugs. The TEXLEISH consortium proposes a new paradigm: inhibiting host-parasite interactions, through targeting Leishmania exoproteome, in
Increase the Therapeutic Index of Antisense Oligonucleotides – Ther-ASO
Antisense oligonucleotides (ASO) therapy can be created for any patient, any target, including targets that have long been considered “un-druggable” by traditional therapies. In 2019, Ionis Pharmaceuticals, announced that more than 12,000 patients have been safety treated with ASO medicines across m
Brain Gene therapy by sonoporation for Fragile X syndrome therapy – FUSBRAIN
Fragile X syndrome (FXS) is the most common cause of hereditary intellectual disability. At present, there is no treatment for this disease, only symptomatic treatments to reduce the effects of the disease are proposed. Gene therapy is a promising therapeutic strategy, however, an effective and non-
Vascularized and perfused skin-on-chip – PerVaSkin
Unveiling skin physiopathology is essential for biological and medicl research. Because animal models fail at predicting human responses to drugs and chemicals in pathology and toxicology, it is crucial to develop skin substitutes with tissue engineering strategies. There are indeed still unmet need
Neural activity of sympathetic nerves as predictive biomarker of rheumatoid arthritis relapses – NeuroInfPredict
Rheumatoid arthritis (RA) is a chronic autoimmune disease affecting approximately 1% of the population, and is characterized by joint inflammation leading to structural damage and disability. RA often exhibits variable disease activity over time with exacerbations (relapses) and periods of low disea
Nanoparticles in blood: understanding and controlling protein corona for optimized nanomedicine – NANOBLORONA
Nanomedicine is a research area that has seen its public interest growing during the last twenty years. The possibility to use and modify physicochemical properties of nanoparticles (NPs) to target and cure any area in the body is becoming more and more encouraging. However, there are still some pr
CK2 inhibitors as chemobiological tools to unravel CK2 role in SARS-COV-2 lifecycle and as potential antivirals with broad-anti-coronavirus activity – CK2COV
In 2020, the global phosphorylation landscape of SARS-CoV-2 infection was revealed, showing that phosphorylation signalling represents a primary host response to viral infection. In this study, casein kinase II (CK2) appeared to be involved in SARS-CoV-2 lifecycle, suggesting that targeting CK2 shou
Development of NanOVEctors for Lysosomal-based therapeutic strategies to combat lysosomal-related neurodegenerative diseases – NOVEL
Neurodegenerative diseases represent some of the greatest challenges for basic science and clinical medicine because of their prevalence, cost, complex biochemistry and pathology, and lack of mechanism-based treatments. Genetic and neuropathological evidence indicates that a likely mechanism linking
Novel Influenza Peptide Inhibitors by Directed Evolution – FluPept
Influenza is a common respiratory disease that affects 10-30% of the population each year and kills 290-650,000 people annually worldwide. Antiviral drugs complement the annual global vaccine strategy, notably when vaccines match poorly with the epidemic strains. They become the first line of defenc
Development of next-generation allosteric compounds for the GLP-1R based on human receptor variants to treat type 2 diabetes – alloGLP1R
The glucagon-like-peptide-1 receptor (GLP-1R), a class B G protein-coupled receptor (GPCR), is a well-validated target for the treatment of type 2 diabetes mellitus (T2DM) with several peptide agonists on the market. These drugs improve glycemic control and reduce body weight but suffer also from si
Treating myocardial infarction using pH-sensitive nanoparticles for FADD silencing – NanoCard
Cardiovascular diseases (CVD) including myocardial infarction (MI) ranks first in worldwide mortality and according to WHO, they will stay at this rank until 2030. Prompt revascularization of the occluded artery to reperfuse the myocardium is the only recommended treatment (by angioplasty or thrombo
Controlled degradation behavior of bioresorbable stent via surface strategy – BIORESORB
Cardiovascular diseases are nowadays the leading causes of death worldwide1, mainly caused by coronary artery disease induced by narrowing or occlusion (stenosis) of the arterial vessels. Common treatments are based on angioplasty, using a tiny balloon and inflating it temporarily to place of a smal
Designing a CAR-based phagocyte therapy for solid tumors – CARpha
A CAR, is a tumor-specific engineered antigen receptor, combining the highly specific binding domain of an antibody to the intracellular signalling domain of a T cell receptor (CD3e, CD28, 4-1BB). Once expressed in T cells, these engineered cells are capable of finding, migrating and killing tumor c
Innovative NIR light responsive nanoparticles for enhanced antibacterial PDT and singlet oxygen mediated antibiotic release – BaXygen
Antibiotics overuses, misuses and environmental factors led to a global increase in antimicrobial resistance - that is responsible of the death of 700,000 people/year, and if no action is taken the World Health Organization estimates that it could cause 10 million deaths/year by 2050. The developmen
Porous hydrogel under perfusion: modeling and optimization of an in vitro model of bone defect reconstruction – HydrOs
Bone is a living tissue that is subjected to various stimuli. Cells receive mechanical, chemical or biophysical signals through their environment. The information translates into a capacity to adapt to any environmental modification. In the context of bone tissue engineering (BTE), this property can
In vivo cardiac targeting of glycan-engineered extracellular vesicles – Exoglyc
The objective of this project is to develop a treatment of heart failure (HF) based on intravenous injections of the extracellular vesicle (EV)-enriched secretome of cardiovascular progenitor cells. The rationale is that the primary mechanism of action of the cells is the paracrine activation of end
CRISPR-Cas9-mediated ON-target genotoxicity – CRISPR-genotox
CRISPR-Cas9 nuclease is a very promising technology for gene therapy. The first clinical trials have started. However, genome editing, to be safe, must be precise and reliable. Genotoxicity at the targeted locus (ON-target) is little studied. Unexpectedly, we observed megabase-scale terminal chromos
Development of a 3D « bronchioid » to model Chronic Obstructive Pulmonary disease – BRONCHIOLE
Chronic obstructive pulmonary disease (COPD) is a major public health disease (i.e., 3rd cause of death worldwide) characterized by persistent airflow limitation, which responds minimally to bronchodilators and corticosteroid therapy. In COPD, both mesenchymal and epithelial cells undergo pathologic
Post exposure vaccines gainst emerging viruses – EXPUNGER
The current pandemic reminds us the necessity to be prepared for the emergence and re-emergence of human pathogens. The World Health Organization has established a list of priority diseases posing the greatest public health risk due to their epidemic potential and requiring massive research effort t
Cocktail of labelled VOC-based probes for biomedicine – Volatolomix
With the emergence of volatolomics, i.e., the discipline that investigates VOCs produced by living systems, the human volatolome (i.e. matrix of VOCs released by an individual) has been emphasized since it can provide valuable insight into biological processes in real-time. Hence, as evidenced by ca
New nanomedicines using enkephalins for pain alleviation, overcoming the side effects of morphine and other opioid derivatives – NANOPAINKILL
This study represents a novel and efficient approach for the treatment inflammatory pain, characterized by the design of squalene-based nanomedicines allowing the specific delivery of Leu-Enkephalin (LENK) neuropeptide into inflamed tissues after intravenous administration. The research project is a
Enzyme-responsive platforms for mitochondria targeted drug delivery – MitoRedAct
In the last decades, mitochondria has emerged as a therapeutic target of interest. This organelle of eukaryotic cells plays an essential role in the cell's energy production. Mitochondrial disorders have been linked to a wide variety of pathologies such as neurodegenerative diseases, metabolic, card
Characterization of a new therapeutic strategy to target the vulnerabilities of small-cell lung cancer. – smallTARGET
Small cell lung cancer is a rare disease that remains untreated. We have recently characterised a protein whose expression appears to be highly specific to this tumor subtype. In this project, we propose to create a new molecule that would combine an antibody (or its fragments) directed against this
Pharmacological approaches for the treatment of NF1 bone manifestations – NFbone
Neurofibromatosis type 1 (NF1) is an autosomal dominant disease due to mutations in the NF1 tumor suppressor gene, encoding the RAS-GTPase activating protein neurofibromin, and affecting 1 in 3000 people. NF1 patients can be affected by a variety of symptoms including cutaneous, neurological, orthop