Philippe JEAN-PIERRE

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• Type de publi. : Communication dans un congrès
• Date de publi. : 28/11/2022
• Auteurs : Sandrine LefrancChie KoderaEric BiotAyoub OuddahAlexandre DurrmeyerMagalie UyttewaalDavid BouchezPhilippe Andrey
• Organismes : Institut Jean-Pierre Bourgin - Sciences du végétal Institut Jean-Pierre Bourgin - Sciences du végétal Institut Jean-Pierre Bourgin - Sciences du végétal Institut Jean-Pierre Bourgin - Sciences du végétal Institut Jean-Pierre Bourgin - Sciences du végétal Institut Jean-Pierre Bourgin - Sciences du végétal Institut Jean-Pierre Bourgin - Sciences du végétal Institut Jean-Pierre Bourgin - Sciences du végétal

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Résumé : How the division plane is positioned during plant cell division plays an important role in the building of specific tissue architectures and organ shapes. Much is known about the molecular and cellular machinery involved in the different steps of cell division but how the positioning and orientation of the division plane is selected remains unclear. Several phenomenological rules have been proposed to relate the geometry of the mother cell to the selection of the division plane. Among these, Errera’s rule is generally accepted as a default principle, according to which cells divide into two daughter cells of equal volumes with a minimum contact interface area. Deviations from this default regime would result from specific signals such as hormonal and mechanical cues. However, much of this view has been derived essentially from 2D analyses of volume-symmetric divisions. Recently, we introduced an original image-based 3D model of cell division that allows to address both symmetric and asymmetric partitionings of the mother cell space. Using this model, we showed that a single rule linking the positioning of the division plane to cell geometry accounted for both stereotyped and variable, symmetric and asymmetric, division patterns in A. thaliana early embryo, thus unifying a range of distinct division patterns. Here, we examined the potential of this approach to decipher division patterns in the shoot apical meristem. A large collection of 3D time-lapse images of developing meristems with fluorescently labeled cell membranes were acquired using confocal microscopy. We designed original image processing pipelines under the BIP software (see companion poster by Biot et al.) to quantify topological, morphological, and geometrical features of tissues, cells and cell divisions. The 3D cell division model was run in mother cells from automatically identified cell divisions and model predictions were compared to observed daughter cell patterns. We report the first results of the quantitative image analyses and model simulations we obtained on meristems from wild-type and from trm678 mutant plants in which the absence of preprophase band alters division patterns.

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• Type de publi. : Communication dans un congrès
• Date de publi. : 27/11/2022
• Auteurs : Olivia Desgué-ItierJean-Philippe JennyLaura SoaresNajwa SharafO. AnnevilleDamien BouffardBrigitte Vincon-LeiteVincent ChanudetPierre-Alain DanisIsabelle DomaisonThéo MazureFrédéric SoulignacViet Tran KhacJean Guillard
• Organismes : Centre Alpin de Recherche sur les Réseaux Trophiques et Ecosystèmes Limniques Centre Alpin de Recherche sur les Réseaux Trophiques et Ecosystèmes Limniques Centre Alpin de Recherche sur les Réseaux Trophiques et Ecosystèmes Limniques Pôle Écla - écosystèmes lacustres Centre Alpin de Recherche sur les Réseaux Trophiques et Ecosystèmes Limniques Swiss Federal Institute of Aquatic Science and Technology [Dübendorf] Laboratoire Eau Environnement et Systèmes Urbains EDF, Hydro Engineering Centre, Environment and Social Department, 73370 Le Bourget-du-Lac, France Pôle Écla - écosystèmes lacustres Centre Alpin de Recherche sur les Réseaux Trophiques et Ecosystèmes Limniques Centre Alpin de Recherche sur les Réseaux Trophiques et Ecosystèmes Limniques CIPEL, International Commission for the protection of Water Lake Geneva, 1260 Nyon, Switzerland Centre Alpin de Recherche sur les Réseaux Trophiques et Ecosystèmes Limniques Centre Alpin de Recherche sur les Réseaux Trophiques et Ecosystèmes Limniques

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Résumé : Climate change modifies globally the thermal regime and solubility of oxygen in lakes, resulting in the alteration of lake habitats. The use of 1D lake models has become the standard in lake researches to evaluate the effects of climate change. However, the required global scale forcing parameters have several limitations, such as the need of downscaling. In this study, several 1D lake models' robustness were tested for long-term variations based on 50±13 years of limnological data collected by the French Observatory of LAkes (OLA). We evaluate the possibility to force mechanistic models by following the long-term evolution of shortwave radiations and air temperatures while providing realistic seasonal trend for the other parameters for which local scale downscaling often lacks accuracy. Then, the effects of climate change on the thermal regime and oxygen solubility were analyzed in the four-largest French peri-Alpine lakes. Our results show that 1D lake models forced by air temperatures and shortwave radiations accurately predict variations in lake thermal regime over the last four to six decades, with RMSE <1.95 °C. During the last three decades, water temperatures have increased by 0.46 °C decade–1 (±0.02 °C) in the epilimnion and 0.33 °C decade–1 (±0.06 °C) in the hypolimnion. Concomitantly and due to thermal change, O2 solubility has decreased by -0.104 mg L–1 decade–1 (±0.005 mg L–1) and -0.096 mg L–1 decade–1 (±0.011 mg L–1) in the epilimnion and hypolimnion, respectively. Based on the ssp370 socio-economic pathway of the IPCC, perialpine lakes could face an increase of 3.80 °C (±0.20 °C) in the next 70 years, accompanied by a decline of 1.0 mg L–1 (±0.1 mg L–1) of O2 solubility. These results suggest important degradation in lake thermal and oxygen conditions and a loss of habitats for endemic species.

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• Type de publi. : Rapport
• Date de publi. : 25/11/2022
• Auteurs : Philippe DrobinskiJordi BadosaIsabelle BilgerBenjamin BrigaudPatricia CrifoAntoine EsnosLouis-Gaëtan GiraudetMarion GosselinMathias GuérineauJean-François GuillemolesFlorence HabetsJean-Pierre LévyJulie MayerBertrand QuélinFlorian RaymondDaniel SuchetQiqi TaoAlexis TantetVincent Viguie
• Organismes : Laboratoire de Météorologie Dynamique (UMR 8539) Laboratoire de Météorologie Dynamique (UMR 8539) Ecosystèmes forestiers Géosciences Paris Saclay Centre de Recherche en Économie et Statistique Laboratoire Techniques, Territoires et Sociétés Centre International de Recherche sur l'Environnement et le Développement Ecosystèmes forestiers Nantes Université - Institut d'Administration des Entreprises - Nantes Institut Photovoltaïque d’Ile-de-France (UMR) Laboratoire de géologie de l'ENS Laboratoire Techniques, Territoires et Sociétés Centre de Recherche en Gestion I3 Ecole des Hautes Etudes Commerciales Laboratoire Dynamiques Sociales et Recomposition des Espaces Institut Photovoltaïque d’Ile-de-France (UMR) Laboratoire de Météorologie Dynamique (UMR 8539) Laboratoire de Météorologie Dynamique (UMR 8539) Centre International de Recherche sur l'Environnement et le Développement

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Fichiers liés : carnets-grec-energie_2022.pdf

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• Type de publi. : Article dans une revue
• Date de publi. : 23/11/2022
• Auteurs : Gaëlle Pinto CardosoMarion Lagrée-ChastanMarion CaserisJoël GaudelusHervé HaasJean-Philippe LeroyPierre BakhacheJean-François PujolAndreas WernerMarie-Aliette DommerguesEmilie PauquetDidier Pinquier
• Organismes : Laboratoire d'Informatique Médicale et Ingénierie des Connaissances en e-Santé Service des maladies infectieuses et tropicales [Rouen]
• Publié dans Frontiers in Pediatrics le 24/10/2020

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Résumé : Background In Europe, meningococcal (Men) vaccines are available against 5 of the 6 serogroups responsible of nearly all cases of invasive meningococcal disease (IMD). Meningococcal vaccination has been introduced in the national immunization programs (NIPs) for children and adolescents of numerous European countries, but with no consistent strategy across countries. Objectives To describe IMD epidemiology, NIPs, and vaccination coverage rates (VCRs) in children and adolescents in 8 Western European countries. Methods Epidemiological data (from 1999 to 2019), NIPs regarding meningococcal vaccination status, and VCRs were collected from the European Centre for Disease Prevention and Control (ECDC) and/or national websites. Results MenB was the most common serogroup. In Belgium, Spain, France, the Netherlands, the United Kingdom (UK), and Portugal, incidence was greater for MenW than MenC. In 2019, MenB risk was covered in 2 countries (Italy, UK). MenC risk was covered in all countries, via MenC only (countries: N = 3), MenACWY only ( N = 2), or MenC (infants/children) and MenACWY (adolescents) ( N = 3) vaccination. VCRs were higher in children than adolescents. Conclusion Our study confirmed the diversity of NIPs, including in neighboring European countries with similar factors like economic resources and epidemiological risk, thus indicating that other factors underlie NIPs. Convergence toward a more common immunization program including MenACWY and MenB vaccination would promote equity and safe travel regarding infectious diseases for young people, and possibly improve the understanding of vaccination by patients and healthcare professionals.

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Fichiers liés : fped-10-1000657.pdf

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• Type de publi. : Pré-publication, Document de travail
• Date de publi. : 22/11/2022
• Auteurs : Marie LabatJ P Couperus CabadağAmin GhaithArie IrmanAnthony BerliouxPhilippe BerteaudFrédéric BlacheStefan BockFrançois BouvetFabien BriquezYen-Yu ChangSébastien CordeAlexander DebusCarlos de OliveiraJean-Pierre DuvalYannick DietrichMoussa El AjjouriChristoph EisenmannJulien GautierRené GebhardtSimon GramsUwe HelbigChristian HerbeauxNicolas HubertCharles KitegiOlena KononenkoMichael KuntzschMaxwell LabergeStéphane LéBruno LeluanAlexandre LoulergueVictor MalkaFabrice MarteauManh Huy N GuyenDriss Oumbarek-EspinosRichard PauschDamien PereiraThomas PüschelJean-Paul RicaudPatrick RommeluereEléonore RousselPascal RousseauSusanne SchöbelMourad SebdaouiKlaus SteinigerKeihan TavakoliCedric ThauryPatrick UferMathieu ValléauMarc VandenbergheJosé VétéranUlrich SchrammMarie-Emmanuelle Couprie
• Organismes : Synchrotron SOLEIL Helmholtz-Zentrum Dresden-Rossendorf Synchrotron SOLEIL Synchrotron SOLEIL Synchrotron SOLEIL Synchrotron SOLEIL Laboratoire d'Optique Appliquée Institute of Radiation Physics [Dresden] Synchrotron SOLEIL Synchrotron SOLEIL Laboratoire d'Optique Appliquée Laboratoire d'Optique Appliquée Weizmann Institute of Science [Rehovot, Israël] DYnamique des Systèmes COmplexes Laboratoire de Physique des Lasers, Atomes et Molécules - UMR 8523 Laboratoire d'Optique Appliquée Laboratoire d'Optique Appliquée Synchrotron SOLEIL

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Résumé : Free-electron lasers generate high-brilliance coherent radiation at wavelengths spanning from the infrared to the X-ray domains. The recent development of short-wavelength seeded free-electron lasers now allows for unprecedented levels of control on longitudinal coherence[1], opening new scientific avenues as ultra-fast dynamics on complex systems and X-ray nonlinear optics. While those devices rely on state-of-the-art large-scale accelerators, advancements on laser-plasma accelerators, which harness giga-volt-per-centimeter accelerating fields, showcase a promising technology as compact drivers for free-electron lasers. Using such miniaturized accelerators, exponential amplification of a shot-noise type of radiation in a self-amplified spontaneous emission configuration was recently achieved [2]. However, employing this compact approach for the delivery of temporally coherent pulses in a controlled manner remained a major challenge. Here, we present the experimental demonstration of a laser-plasma accelerator driven free-electron laser in a seeded configuration, where control over the radiation wavelength is accomplished. Furthermore, the appearance of interference fringes, resulting from the interaction between the phase-locked emitted radiation and the seed, confirms longitudinal coherence. Building on our scientific achievements, we anticipate a straightforward scaling to extreme-ultraviolet wavelengths, paving the way towards university-scale free-electron lasers, unique tools for a multitude of applications. [1] Meyer, M. FELs of europe: Whitebook on science with free electron lasers 8–19 (2016). [2] Wang, W. et al. Free-electron lasing at 27 nanometres based on a laser wakefield accelerator.

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• Type de publi. : Article dans une revue
• Date de publi. : 22/11/2022
• Auteurs : Lydie LemoineVirginie AdamXavier GalusPascale SilesAgnès CoulonJeannette Grenier-DesforgesJoseph OrabonaIsabelle KergastelPierre WagnerJulia SalleronPriscillia TostiCécile Huin-SchohnJean-Louis MerlinRémi EtiennePhilippe Henrot
• Organismes : Institut de Cancérologie de Lorraine - Alexis Vautrin [Nancy] Institut de Cancérologie de Lorraine - Alexis Vautrin [Nancy] Institut de Cancérologie de Lorraine - Alexis Vautrin [Nancy] Hôpital de la Timone [CHU - APHM] Département cancer environnement (Centre Léon Bérard - Lyon) CHU de Bordeaux Pellegrin [Bordeaux] Centre Hospitalier Bastia Centre Hospitalier Régional Universitaire de Brest Centre Paul Strauss Institut de Cancérologie de Lorraine - Alexis Vautrin [Nancy] Institut de Cancérologie de Lorraine - Alexis Vautrin [Nancy] Institut de Cancérologie de Lorraine - Alexis Vautrin [Nancy] Centre de Recherche en Automatique de Nancy Institut de Cancérologie de Lorraine - Alexis Vautrin [Nancy] Institut de Cancérologie de Lorraine - Alexis Vautrin [Nancy] Institut de Cancérologie de Lorraine - Alexis Vautrin [Nancy]
• Publié dans Frontiers in Psychology le 02/11/2020

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Résumé : Background Surgery is a cornerstone of breast cancer management. Prior to surgery, a wire marker is placed at the site of the tumor, to enable the surgeon to accurately localize the lesion during later surgery. This procedure can generate considerable anxiety for many patients. We investigated the value of conversational hypnosis (CH) in reducing anxiety in patients undergoing preoperative wire placement under radiographic control. Methods Randomized, multicentre study in 7 centers in France. Inclusion criteria were patients aged >18 years with an Eastern Cooperative Oncology Group performance status ≤2, scheduled to undergo preoperative wire placement in one or several breast lesions. Patients were randomized in a 1:1 ratio, stratified by center to undergo preoperative wire placement with or without the use of CH by a radiological technician trained in the CH technique. The primary endpoint was the percentage of patients with an anxiety score ≥ 6 on a visual analog scale ranging from 0 (absence of anxiety) to 10 (maximal anxiety). Secondary endpoints were pain score, perceived duration reported by the patient, technician satisfaction with their relationship with the patient, and ease of marker insertion reported by the radiologist. Semi-structured interviews were performed with patients to assess their perception of the marker placement procedure. Results The trial was prematurely interrupted for futility after a planned interim analysis after accrual of 167 patients, i.e., half the planned sample size. Prior to marker placement, 29.3% ( n = 24) of patients in the control group had an anxiety score ≥ 6, versus 42.3% ( n = 33) in the CH group ( p = 0.08). After marker placement, the change of anxiety score was not significantly different between groups (11.0% ( n = 9) versus 14.3% ( n = 11), p = 0.615). There was no significant difference in any of the secondary endpoints. In the interviews, patients from both groups frequently spoke of a feeling of trust. Conclusion This study failed to show a benefit of conversational hypnosis on anxiety in patients undergoing marker placement prior to surgery for breast cancer. The fact that some caregivers had learned this personalized therapeutic communication technique may have had a positive impact on the whole caregiving team. Trial registration The study was registered with ClinicalTrials.gov (NCT02867644).

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• Type de publi. : Communication dans un congrès
• Date de publi. : 21/11/2022
• Auteurs : David SiniscalcoLaurence PessoniGuillaume VignaudJean-François TassinJean-François BardeauAnne BoussonniereAnne-Sophie CastanetPhilippe LeclèrePierre NickmilderLaurent BillonN. Delorme
• Organismes : Institut des Molécules et Matériaux du Mans Institut de Recherche Dupuy de Lôme Institut des Molécules et Matériaux du Mans Institut des Molécules et Matériaux du Mans

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• Type de publi. : Article dans une revue
• Date de publi. : 21/11/2022
• Auteurs : Philippe Boulanger
• Organismes : Sorbonne Université
• Publié dans Revue de Géographie Historique le 27/10/2020

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• Type de publi. : Article dans une revue
• Date de publi. : 20/11/2022
• Auteurs : Ivan AlonsoCristiano AlpigianiBrett AltschulHenrique AraujoGianluigi ArduiniJan ArltLeonardo BadurinaAntun BalazSatvika BandarupallyBarry C Barish Michele BaroneMichele BarsantiSteven BassAngelo BassiBaptiste BattelierCharles F. A. BaynhamQuentin BeaufilsAleksandar BelicJoel BergéJose BernabeuAndrea BertoldiRobert BinghamS. BizeDiego BlasKai BongsPhilippe BouyerCarla BraitenbergChristian BrandClaus BraxmaierAlexandre BressonOliver BuchmuellerDmitry BudkerLuıs BugalhoSergey BurdinLuigi Cacciapuoti Simone CallegariXavier CalmetDavide CalonicoBenjamin CanuelLaurentiu-Ioan CarameteOlivier CarrazDonatella CassettariPratik ChakrabortySwapan ChattopadhyayUpasna ChauhanXuzong ChenYu-Ao ChenMaria Luisa ChiofaloJonathon ColemanRobin CorgierJ. P. CotterA. Michael CruiseYanou CuiGavin DaviesAlbert de RoeckMarcel DemarteauAndrei DereviankoMarco Di ClementeGoran S. DjordjevicSandro DonadiOlivier DorePeter DornanMichael DoserGiannis DrougakisJacob DunninghamSajan EasoJoshua EbyGedminas ElertasJohn EllisDavid EvansPandora ExamiliotiPavel FadeevMattia FanıFarida FassiMarco FattoriMichael A. FedderkeDaniel FeleaChen-Hao FengJorge FerrerasRobert FlackVictor V. FlambaumRene ForsbergMark FromholdNaceur GaaloulBarry M. GarrawayMaria GeorgousiAndrew GeraciKurt GibbleValerie GibsonPatrick GillGian F. GiudiceJon GoldwinOliver GouldOleg GrachovPeter W. GrahamDario GrassoPaul F. GriffinChristine GuerlinMustafa GundoganRatnesh K GuptaMartin HaehneltEkim T. HanımeliLeonie HawkinsAurelien HeesVictoria A. HendersonWaldemar HerrSven HerrmannThomas HirdRichard HobsonVincent HockJason M. HoganBodil HolstMichael HolynskiUlf IsraelssonPeter JeglicPhilippe JetzerGediminas JuzeliunasRainer KaltenbaekJernej F. KamenikAlex KehagiasTeodora KirovaMarton Kiss-TothSebastian KokeShimon KolkowitzGeorgy KornakovTim KovachyMarkus KrutzikMukesh KumarPradeep KumarClaus LammerzahlGreg LandsbergChristophe Le Poncin-LafitteDavid R. LeibrandtThomas LevequeMarek LewickiRui LiAnna LipniackaChristian Lisdat Mia LiuJ. L. Lopez-GonzalezSina LorianiJorma LoukoGiuseppe Gaetano LucianoNathan LundbladSteve MaddoxM. A. MahmoudAzadeh MaleknejadJohn March-RussellDidier MassonnetChristopher MccabeMatthias MeisterTadej MeznarsicSalvatore MicalizioFederica MigliaccioPeter MillingtonMilan MilosevicJeremiah MitchellGavin W. MorleyJurgen MullerEamonn MurphyOzgur E. MustecaplıogluVal OsheaDaniel K. L. OiJudith OlsonDebapriya PalDimitris G. PapazoglouElizabeth PasatembouMauro PaternostroKrzysztof PawlowskiEmanuele PelucchiFranck Pereira dos SantosAchim PetersIgor PikovskiApostolos PilaftsisAlexandra PintoMarco PrevedelliVishnupriya Puthiya-VeettilJohn QuenbyJohann RafelskiErnst M. RaselCornelis RavensbergenMirko ReguzzoniAndrea RichaudIsabelle RiouMarkus RothacherAlbert RouraAndreas RuschhauptDylan O. SabulskyMarianna SafronovaIppocratis D. SaltasLeonardo SalviMuhammed SameedPandey SaurabhStefan SchafferStephan SchillerManuel SchillingVladimir SchkolnikDennis SchlippertPiet O. SchmidtHarald SchnatzJean SchneiderUlrich SchneiderFlorian SchreckChristian SchubertArmin ShayeghiNathaniel SherrillIan ShipseyCarla SignoriniRajeev SinghYeshpal SinghConstantinos SkordisAugusto SmerziCarlos F. SopuertaFiodor SorrentinoParaskevas SphicasYevgeny V. StadnikPetruta StefanescuMarco G. TaralloSilvia TentindoGuglielmo M. TinoJonathan N. TinsleyVincenza TornatorePhilipp TreutleinAndrea TrombettoniYu-Dai TsaiPhilip TuckeyMelissa A UchidaTristan ValenzuelaMathias van Den BosscheVille VaskonenGunjan VermaFlavio VetranoChristian VogtWolf von KlitzingPierre WallerReinhold WalserEric Wille Jason WilliamsPatrick WindpassingerUlric WittrockPeter WolfMarian WoltmannLisa WornerAndre XuerebMohamed YahiaEfe YazganNan YuNassim ZahzamEmmanuel Zambrini CruzeiroMingsheng ZhanXinhao ZouJure ZupanErik Zupanic
• Organismes : DPHY, ONERA, Université Paris Saclay [Châtillon] DPHY, ONERA, Université Paris Saclay [Palaiseau] Laboratoire Photonique, Numérique et Nanosciences Laboratoire national de métrologie et d'essais - Systèmes de Référence Temps-Espace Laboratoire Univers et Théories DPHY, ONERA, Université Paris Saclay [Palaiseau]
• Publié dans European physical journal quantum technology le 03/02/2016

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Résumé : We summarise the discussions at a virtual Community Workshop on Cold Atoms in Space concerning the status of cold atom technologies, the prospective scientific and societal opportunities offered by their deployment in space, and the developments needed before cold atoms could be operated in space. The cold atom technologies discussed include atomic clocks, quantum gravimeters and accelerometers, and atom interferometers. Prospective applications include metrology, geodesy and measurement of terrestrial mass change due to, e.g., climate change, and fundamental science experiments such as tests of the equivalence principle, searches for dark matter, measurements of gravitational waves and tests of quantum mechanics. We review the current status of cold atom technologies and outline the requirements for their space qualification, including the development paths and the corresponding technical milestones, and identifying possible pathfinder missions to pave the way for missions to exploit the full potential of cold atoms in space. Finally, we present a first draft of a possible road-map for achieving these goals, that we propose for discussion by the interested cold atom, Earth Observation, fundamental physics and other prospective scientific user communities, together with ESA and national space and research funding agencies.

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Fichiers liés : s40507-022-00147-w.pdf

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• Type de publi. : Pré-publication, Document de travail
• Date de publi. : 18/11/2022
• Auteurs : Mathieu MévelVirginie PichardMohammed BouzelhaDimitri Alvarez-DortaPierre-Alban LalysNathalie ProvostMarine AllaisAlexandra MendesElodie LandagarayJean‐baptiste DucloyerAnne GalyNicole BrumentGaëlle M LefevreSebastien G. GouinCarolina IsiegasGuylène Le MeurT. CroninCaroline Le GuinerMichel WeberPhilippe P. MoullierEduard AyusoOumeya Adjali
• Organismes : Laboratoire de Thérapie Génique Translationnelle des Maladies Génétiques / Translational Research in Gene Therapy - UMR_S 1089 Laboratoire de Thérapie Génique Translationnelle des Maladies Génétiques / Translational Research in Gene Therapy - UMR_S 1089 Laboratoire de Thérapie Génique Translationnelle des Maladies Génétiques / Translational Research in Gene Therapy - UMR_S 1089 Chimie Et Interdisciplinarité : Synthèse, Analyse, Modélisation Chimie Et Interdisciplinarité : Synthèse, Analyse, Modélisation Laboratoire de Thérapie Génique Translationnelle des Maladies Génétiques / Translational Research in Gene Therapy - UMR_S 1089 Laboratoire de Thérapie Génique Translationnelle des Maladies Génétiques / Translational Research in Gene Therapy - UMR_S 1089 Laboratoire de Thérapie Génique Translationnelle des Maladies Génétiques / Translational Research in Gene Therapy - UMR_S 1089 Chimie Et Interdisciplinarité : Synthèse, Analyse, Modélisation Laboratoire de Thérapie Génique Translationnelle des Maladies Génétiques / Translational Research in Gene Therapy - UMR_S 1089 Coave Therapeutics Coave Therapeutics Coave Therapeutics Chimie Et Interdisciplinarité : Synthèse, Analyse, Modélisation Laboratoire de Thérapie Génique Translationnelle des Maladies Génétiques / Translational Research in Gene Therapy - UMR_S 1089 Laboratoire de Thérapie Génique Translationnelle des Maladies Génétiques / Translational Research in Gene Therapy - UMR_S 1089 Laboratoire de Thérapie Génique Translationnelle des Maladies Génétiques / Translational Research in Gene Therapy - UMR_S 1089 Laboratoire de Thérapie Génique Translationnelle des Maladies Génétiques / Translational Research in Gene Therapy - UMR_S 1089 Laboratoire de Thérapie Génique Translationnelle des Maladies Génétiques / Translational Research in Gene Therapy - UMR_S 1089 Laboratoire de Thérapie Génique Translationnelle des Maladies Génétiques / Translational Research in Gene Therapy - UMR_S 1089 Laboratoire de Thérapie Génique Translationnelle des Maladies Génétiques / Translational Research in Gene Therapy - UMR_S 1089 Laboratoire de Thérapie Génique Translationnelle des Maladies Génétiques / Translational Research in Gene Therapy - UMR_S 1089

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Résumé : Inherited retinal diseases are a leading and untreatable cause of blindness and are therefore candidate diseases for gene therapy. Recombinant vectors derived from adeno-associated virus (rAAV) are currently the most promising vehicles for in vivo therapeutic gene delivery to the retina. However, there is a need for novel AAV-based vectors with greater efficacy for ophthalmic applications, as underscored by recent reports of dose-related inflammatory responses in clinical trials of rAAV-based ocular gene therapies. Improved therapeutic efficacy of vectors would allow for decreases in the dose delivered, with consequent reductions in immune reactions. Here, we describe the development of new rAAV vectors using bioconjugation chemistry to modify the rAAV capsid, thereby improving the therapeutic index. Covalent coupling of a mannose ligand, via the formation of a thiourea bond, to the amino groups of the rAAV capsid significantly increases vector transduction efficiency of both rat and nonhuman primate retinas. These optimized rAAV vectors have important implications for the treatment of a wide range of retinal diseases.

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Fichiers liés : ManAAV_MainManuscriptHAL.pdf

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