Publications by authors named "J Oki"
Background: Cerebral blood flow normally places a limit on the magnitude of brain vascular permeability (P) that can be measured in vivo. At normal cerebral blood flow, this limit falls at the lower end of lipophilicity for most FDA-approved CNS drugs. In this study, we report on two methods that can be used to overcome this limitation and measure brain vascular permeability values that are up to ~1000 times higher using the in situ brain perfusion technique.
View Article and Find Full Text PDFType II Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)-Cas9 nucleases have been extensively used in biotechnology and therapeutics. However, many applications are not possible owing to the size, targetability, and potential off-target effects associated with currently known systems. In this study, we identified thousands of CRISPR type II effectors by mining an extensive, genome-resolved metagenomics database encompassing hundreds of thousands of microbial genomes.
View Article and Find Full Text PDFDevelopment of medicines using gene editing has been hampered by enzymological and immunological impediments. We described previously the discovery and characterization of improved, novel gene-editing systems from metagenomic data. In this study, we substantially advance this work with three such gene-editing systems, demonstrating their utility for cell therapy development.
View Article and Find Full Text PDFArticle Synopsis
- - Inhibitors of BET proteins might seem like a good option for preventing SARS-CoV-2 because they lower levels of ACE2, but this strategy could backfire.
- - Using BET inhibitors increases the severity of SARS-CoV-2 infections by reducing critical antiviral responses and interferon production, potentially leading to higher viral replication and mortality in infected cells and mice.
- - The envelope (E) protein of SARS-CoV-2 has evolved to suppress interferon responses by targeting BET proteins, suggesting that treating with BET inhibitors could worsen outcomes instead of helping.
Article Synopsis
- Interferon can limit SARS-CoV-2 replication, but only a few Interferon Stimulated Genes (ISGs) with antiviral properties have been discovered.
- A CRISPR/Cas9 screening identified DAXX as a potent inhibitor of SARS-CoV-2, showing that its basic expression can restrict virus replication, especially during early infection stages.
- The study revealed that SARS-CoV-2 triggers DAXX's movement to the cytoplasm and promotes its degradation through mechanisms involving the viral protease PLpro and the proteasome, illustrating a viral strategy to evade DAXX's inhibitory effects.