BLV: Lessons on vaccine development

Vaccination against retroviruses is a challenge because of their ability to stably integrate into the host genome, undergo long-term latency in a proportion of infected cells and thereby escape immune response. Since clearance of the virus is almost impossible once infection is established, the primary goal is to achieve sterilizing immunity. Besides efficacy, safety is the major issue since vaccination has been associated with increased infection or reversion to pathogenicity. In this review, we discuss the different issues that we faced during the development of an efficient vaccine against bovine leukemia virus (BLV). We summarize the historical failures of inactivated vaccines, the efficacy and safety of a live-attenuated vaccine and the economical constraints of further industrial development.Fil: Abdala, Alejandro Ariel. Instituto Nacional de Tecnología Agropecuaria. Centro Regional Santa Fe. Estación Experimental Agropecuaria Rafaela; ArgentinaFil: Alvarez, Irene. Instituto Nacional de Tecnología Agropecuaria. Centro de Investigación En Ciencias Veterinarias y Gastronómicas. Instituto de Virología E Innovaciones Tecnológicas. - Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Virología e Innovaciones Tecnológicas; ArgentinaFil: Brossel, Hélène. Université de Liège; BélgicaFil: Calvinho, Luis Fernando. Instituto Nacional de Tecnología Agropecuaria. Centro Regional Santa Fe. Estación Experimental Agropecuaria Rafaela; ArgentinaFil: Carignano, Hugo Adrián. Instituto Nacional de Tecnología Agropecuaria. Centro de Investigación En Ciencias Veterinarias y Gastronómicas. Instituto de Virología E Innovaciones Tecnológicas. - Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Virología e Innovaciones Tecnológicas; ArgentinaFil: Franco, Lautaro Nahuel. Instituto Nacional de Tecnología Agropecuaria. Centro de Investigación En Ciencias Veterinarias y Gastronómicas. Instituto de Virología E Innovaciones Tecnológicas. - Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Virología e Innovaciones Tecnológicas; ArgentinaFil: Gazon, Hélène. Université de Liège; BélgicaFil: Gillissen, Christelle. Université de Liège; BélgicaFil: Hamaidia, Malik. Université de Liège; BélgicaFil: Hoyos, Clotilde. Université de Liège; BélgicaFil: Jacques, Jean Rock. Université de Liège; BélgicaFil: Joris, Thomas. Université de Liège; BélgicaFil: Laval, Florent. Université de Liège; BélgicaFil: Petersen Cruceño, Marcos Iván. Instituto Nacional de Tecnología Agropecuaria. Centro de Investigación En Ciencias Veterinarias y Gastronómicas. Instituto de Virología E Innovaciones Tecnológicas. - Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Virología e Innovaciones Tecnológicas; ArgentinaFil: Porquet, Florent. Université de Liège; BélgicaFil: Porta, Natalia Gabriela. Instituto Nacional de Tecnología Agropecuaria. Centro de Investigación En Ciencias Veterinarias y Gastronómicas. Instituto de Virología E Innovaciones Tecnológicas. - Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Virología e Innovaciones Tecnológicas; ArgentinaFil: Ruiz, Vanesa. Instituto Nacional de Tecnología Agropecuaria. Centro de Investigación En Ciencias Veterinarias y Gastronómicas. Instituto de Virología E Innovaciones Tecnológicas. - Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Virología e Innovaciones Tecnológicas; ArgentinaFil: Safari, Roghaiyeh. Université de Liège; BélgicaFil: Suárez Archilla, Guillermo. Instituto Nacional de Tecnología Agropecuaria. Centro Regional Santa Fe. Estación Experimental Agropecuaria Rafaela; ArgentinaFil: Trono, Karina Gabriela. Instituto Nacional de Tecnología Agropecuaria. Centro de Investigación En Ciencias Veterinarias y Gastronómicas. Instituto de Virología E Innovaciones Tecnológicas. - Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Virología e Innovaciones Tecnológicas; ArgentinaFil: Willems, Luc. Université de Liège; Bélgic

Epigenetic silencing of HTLV-1 expression by the HBZ RNA through interference with the basal transcription machinery

FNRS; PDR T.0261.20; Télévie (7.4599.19); Fonds Spéciaux pour la Recherche of Ulieg

BIRDY : BIRDY: an interplanetary CubeSat to collect radiation data on the way to Mars and back

International audienceThe studies of the space radiations are facing a lack of observational data. Simultaneous measurements from multiple locations in the solar system are necessary to properly assess the knowledge about the solar wind and the cosmic rays. A specialized CubeSat is a smart and cheap solution to take part in the global effort: a new concept for autonomous space probes will be demonstrated by BIRDY. Moreover the "CubeSat" standard allows numerous students to get involved in the BIRDY team, managed by two major institutions for space science and technology, in France at the Paris Observatory and in Taiwan at the National Cheng Kung University. A prototype shall be ready to fly in Geostationary Transfer Orbit from 2018, before a flight model being sent on a free-return Earth-Mars-Earth trajectory

BIRDY : BIRDY: an interplanetary CubeSat to collect radiation data on the way to Mars and back

International audienceThe studies of the space radiations are facing a lack of observational data. Simultaneous measurements from multiple locations in the solar system are necessary to properly assess the knowledge about the solar wind and the cosmic rays. A specialized CubeSat is a smart and cheap solution to take part in the global effort: a new concept for autonomous space probes will be demonstrated by BIRDY. Moreover the "CubeSat" standard allows numerous students to get involved in the BIRDY team, managed by two major institutions for space science and technology, in France at the Paris Observatory and in Taiwan at the National Cheng Kung University. A prototype shall be ready to fly in Geostationary Transfer Orbit from 2018, before a flight model being sent on a free-return Earth-Mars-Earth trajectory

BIRDY : BIRDY: an interplanetary CubeSat to collect radiation data on the way to Mars and back

International audienceThe studies of the space radiations are facing a lack of observational data. Simultaneous measurements from multiple locations in the solar system are necessary to properly assess the knowledge about the solar wind and the cosmic rays. A specialized CubeSat is a smart and cheap solution to take part in the global effort: a new concept for autonomous space probes will be demonstrated by BIRDY. Moreover the "CubeSat" standard allows numerous students to get involved in the BIRDY team, managed by two major institutions for space science and technology, in France at the Paris Observatory and in Taiwan at the National Cheng Kung University. A prototype shall be ready to fly in Geostationary Transfer Orbit from 2018, before a flight model being sent on a free-return Earth-Mars-Earth trajectory

BIRDY: an interplanetary CubeSat to collect radiation data on the way to Mars and back to prepare the future manned missions

International audienc

DMPK promoter silencing by CRISPRi as a new therapeutic strategy in myotonic dystrophy type 1

"a. IntroductionMyotonic dystrophy type 1 (DM1) is a life threatening disease and causes severe physical and mental disabilities. Unfortunately, there are currently only symptomatic treatments. Therefore, our team aims at elaborating a new curative approach which consists in the DMPK promoter silencing by the CRISPRi system.b. MethodsThe DMPK promoter inhibition capacity of CRISPRi was tested in immortalized myoblasts from DM1 patients. For this purpose, lentiviral particles were produced using CRISPRi plasmids with their own sgRNAs. Next, these myoblasts were transduced and selected with blasticidin. Then, total DMPK mRNA was titrated by RT-qPCR and nuclear DMPK RNA foci were determinated by FISH.c. ResultsSome sgRNAs lead to near 70% inhibition of DMPK transcription as well as foci average particules in DM1 transduced myoblasts.d. ConclusionsThe CRISPRi system is able to efficiently prevent the DMPK mRNA production and foci formation in myoblast.

Specific DMPK-promoter targeting by CRISPRi reverses myotonic dystrophy type 1-associated defects in patient muscle cells

Myotonic dystrophy type 1 (DM1) is a neuromuscular disease that originates from an expansion of CTG microsatellites in the 3′ untranslated region of the DMPK gene, thus leading to the expression of transcripts containing expanded CUG repeats (CUGexp). The pathophysiology is explained by a toxic RNA gain of function where CUGexp RNAs form nuclear aggregates that sequester and alter the function of MBNL splicing factors, triggering splicing misregulation linked to the DM1 symptoms. There is currently no cure for DM1, and most therapeutic strategies aim at eliminating CUGexp-DMPK transcripts. Here, we investigate a DMPK-promoter silencing strategy using CRISPR interference as a new alternative approach. Different sgRNAs targeting the DMPK promoter are evaluated in DM1 patient muscle cells. The most effective guides allowed us to reduce the level of DMPK transcripts and CUGexp-RNA aggregates up to 80%. The CUGexp-DMPK repression corrects the overall transcriptome, including spliceopathy, and reverses a physiological parameter in DM1 muscle cells. Its action is specific and restricted to the DMPK gene, as confirmed by genome-wide expression analysis. Altogether, our findings highlight DMPK-promoter silencing by CRISPRi as a promising therapeutic approach for DM1