Agency: Cordis | Branch: FP7 | Program: CP-IP | Phase: HEALTH.2010.2.3.3-2 | Award Amount: 21.90M | Year: 2010
RNA virus infections kill millions of humans annually, largely due to the lack of suitable vaccines and drugs to control them. This problem is addressed in this FP7 call and in response a consortium of Europes and Asias leading molecular virologists, structural biologists, medicinal chemists and bioinformaticians has been brought together to generate a state-of-the-art drug discovery and design programme. The project aims to identify Small molecule Inhibitor Leads Versus Emerging and neglected RNA viruses (SILVER). It will focus its activities on selected medically important RNA viruses for which the development of drugs is considered essential (Dengue-, entero- and paramyxoviruses), whereas other relatively neglected and/or emerging RNA viruses will be explored to identify the most promising viral protein targets and antiviral compounds. A pipeline strategy has been developed to enable the inclusion in SILVER of viruses at all levels of existing knowledge. Targets for potential drugs include infectious virus, structurally characterised viral enzymes and other proteins. Leads for currently available antiviral drugs have been identified by screening compound libraries in virus-infected cell culture systems and in vitro assays using purified viral enzymes. Selective inhibitors of viral replication have also been (and are being) derived using detailed structural knowledge of viral proteins and structure-based drug design. Hits will be assayed using individual viral protein targets and replicative proteins in complex with viral RNA. The potential protective activity of the most potent inhibitors, that have a favourable (in vitro) ADME-tox profile, will be assessed in relevant infection models in animals. Licenses on promising compounds or compound classes will be presented to the interested pharmaceutical industry. The SILVER consortium will be well placed to play a major role in contributing to the international effort to develop strategies to improve world health.
Agency: Cordis | Branch: FP7 | Program: MC-ITN | Phase: FP7-PEOPLE-2010-ITN | Award Amount: 4.98M | Year: 2011
Virus infections remain a major cause of disease, with dramatic costs in mortality, morbidity, and economic loss worldwide. There is an unmet need for potent antiviral drugs, in particular against viruses with a (\)RNA genome which include many important pathogens of humans and animals. Antiviral drug development requires a detailed understanding of virus replication and effective translation of this knowledge into drug discovery. Europe needs well-trained experts with multidisciplinary skills to advance this field. However, few, if any, European training institutes have the broad know-how required to provide such a comprehensive training programme. The EUVIRNA partnership aims to fill this gap with the proposed EUVIRNA training programme. The EUVIRNA partnership consists of six outstanding European academic partners and four industrial partners (one pharmaceutical R&D company and three SMEs), and an associated partner (SME specialized in education). All EUVIRNA partners are recognized leaders in their field, ensuring state-of-the-art training possibilities, and their skills are highly complementary. Three Visiting Researchers will complement the expertise of the partners. EUVIRNA aims to introduce 18 ESRs and 2 ERs to state-of-the-art knowledge and technology applied in molecular virology and antiviral therapy, with both local and network-wide training activities. Individual research projects, research training workshops and intersectoral secondments will be supplemented with complementary skills courses to improve career development and perspectives. The industrial partners are actively involved in the entire programme, and will furthermore organize a 1-week industry-oriented conference aimed at further bridging the gap between academia and industry. Thus, EUVIRNA offers talented researchers a multidisciplinary and intersectoral training programme and prepares them for a future leading role in European molecular virology research and antiviral dru
Naumann K.,Riboxx GmbH |
Wehner R.,Carl Gustav Carus Institute |
Schwarze A.,Carl Gustav Carus Institute |
Petzold C.,Riboxx GmbH |
And 3 more authors.
Clinical and Developmental Immunology | Year: 2013
Toll-like receptor (TLR) 3 agonists emerged as attractive candidates for vaccination strategies against tumors and pathogens. An important mechanism of action of such agonists is based on the activation of TLR3-expressing dendritic cells (DCs), which display a unique capacity to induce and stimulate T-cell responses. In this context, it has been demonstrated that targeting of TLR3 by double-stranded RNA such as poly(I:C) results in potent activation of DCs. Major disadvantages of poly(I:C) comprise its undefined chemical structure and very poor homogeneity, with subsequent unpredictable pharmacokinetics and high toxicity. In the present study, we evaluated the physicochemical properties and biological activity of the novel TLR3 agonist RGC100. RGC100 has a defined chemical structure, with a defined length (100 bp) and molecular weight (64.9 KDa) and a good solubility. RGC100 is stable in serum and activates myeloid DCs through TLR3 targeting, as evidenced by gene silencing experiments. Activation of mouse and human myeloid CD1c+ DCs by RGC100 leads to secretion of several proinflammatory cytokines. In addition, RGC100 improves the ability of CD1c+ DCs to stimulate T-cell proliferation. Due to its physicochemical properties and its immunostimulatory properties, RGC100 may represent a promising adjuvant for prophylactic and therapeutic vaccination strategies. © 2013 Kai Naumann et al.
Nolte A.,University of Tübingen |
Ott K.,University of Tübingen |
Rohayem J.,Riboxx GmbH |
Rohayem J.,TU Dresden |
And 3 more authors.
New Biotechnology | Year: 2013
Objective: There is a broad therapeutic potential for the application of small interfering RNAs (siRNAs). However, one has to ensure that siRNAs act specifically, only targeting the expression of one gene. Off-target effects raised by the sense strand have to be eliminated. Methods and results: We examined a particular bidirectional siRNA molecule, able to knockdown intercellular adhesion molecule-1 (ICAM-1) and tumor necrosis factor receptor-1 (TNFR-1) by the sense or antisense strand, respectively. Transfection of human venous endothelial cells with an unmodified siRNA molecule led to equal silencing of ICAM-1 and TNFR-1. In contrast, modified siRNA was able to knockdown ICAM-1 and TNFR-1 separately, with only the antisense strand. Discussion: We found the modified siRNAs to inhibit off-target effects originated by the sense strand. Our approach demonstrates one possibility to modify siRNAs before starting a clinical approach to eliminate off-target effects. © 2012 Elsevier B.V.
RiboxX GmbH | Date: 2010-10-21
The present invention relates to a method for exponential amplification of RNA using a primer independent RNA-dependent RNA polymerase (RdRp) wherein reactants are premixed cycle and then transferred into the reaction chamber in which the steps of polymerisation of the complementary strand and separation of the resulting double-stranded RNA occur. The invention also relates to a RNA reactor for carrying out the exponential RNA amplification.
RiboxX GmbH | Date: 2010-10-21
The present invention relates to a method for exponential amplification of RNA in vitro by using a thermostable RNA-dependent RNA polymerase (RdRp) of a sapovirus or norovirus.
RiboxX GmbH | Date: 2014-12-16
The present invention relates to polyC:poly(G/1) dsRNAs for triggering innate immunity, in particular through toll-like receptor 3 (TLR-3) and, optionally, RIG-I or RIG-Ilike receptors (RLRs), as well as compositions and medicaments containing such dsRNAs, methods for their production and their use in medicine, especially immunostimulation and prevention and/or therapy of infections and tumor diseases.
RiboxX GmbH | Date: 2012-06-13
The present invention relates to a kit for carrying out methods for the detection of target RNA sequences making use of strand displacement techniques employing RNA-dependent RNA polymerases of viruses of the Caliciviridae family having RNA-oligonucleotide duplex separation activity and being capable of de novo RNA synthesis in the absence of a primer.
Riboxx Gmbh | Date: 2012-10-31
The present invention relates to a ribonucleic acid (RNA) of double-stranded structure which is capable of triggering Toll-like receptor 3 (TLR-3) and which shows an increased serum stability while simultaneously being unable to be processed by the DICER complex.
Riboxx Gmbh | Date: 2010-02-24
The present invention relates to small-interfering RNA molecules displaying an increased thermodynamic stability at the 3 end of the antisense strand (guide strand) and the 5 end of the sense strand (passenger strand), respectively, in comparison to the base pairing in the seed region. The siRNAs of the present invention display an increased knock-down activity against targeted genes and show an improved resistance to RNAses, in particular serum RNAses. The present invention also relates to a method for the production of the siRNA molecules, a method of target-specific RNA interference making use of the improved siRNA molecules of the invention and pharmaceutical compositions containing the siRNA molecules.