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Genetic Engineering Publications - GEG Tech top picks
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In this work, the authors used the CRISPR system to define cellular proteins essential to elicitation of the antiviral activity for alphavirus, Venezuelan Equine Encephalitis virus, and Sindbis virus. Their results allowed the identification of IRF3, the IRF3-activating adaptor molecule STING, and the IFN-associated transcription factor STAT1 as required for observed gene induction and antiviral effects. In vivo stimulation of STING-dependent activity by an unrelated small molecule in a mouse model of Chikungunya virus infection blocked viremia demonstrating that pharmacologic activation of this signaling pathway may represent a feasible strategy for combating emerging Alphaviruses. 
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Here, the scientists demonstrate that mRNA lipoplexes induce a potent type I IFN response upon subcutaneous, intradermal and intranodal injection. Regardless of the route of immunization applied, these type I IFNs interfered with the generation of potent cytolytic T cell responses. Most importantly, blocking type I IFN signalling at the site of immunization through the use of an IFNAR blocking antibody greatly enhanced the prophylactic and therapeutic anti-tumour efficacy of mRNA lipoplexes in the highly aggressive B16 melanoma model. As type I IFN induction appears to be inherent to the mRNA itself rather than to unique properties of the mRNA lipoplex formulation, preventing type I IFN induction and/or IFNAR signalling at the site of immunization might constitute a widely applicable strategy to improve the potency of mRNA vaccination