Neurodegenerative disorders are a major public health problem because of the high frequency of these diseases. Genome editing with the CRISPR/Cas9 system is making it possible to modify the sequence of genes linked to these disorders. We designed the KamiCas9 self-inactivating editing system to achieve transient expression of the Cas9 protein and high editing efficiency. In the first application, the gene responsible for Huntington's disease (HD) was targeted in adult mouse neuronal and glial cells. Mutant huntingtin (HTT) was efficiently inactivated in mouse models of HD, leading to an improvement in key markers of the disease. Sequencing of potential off-targets with the constitutive Cas9 system in differentiated human iPSC revealed a very low incidence with only one site above background level. This off-target frequency was significantly reduced with the KamiCas9 system. These results demonstrate the potential of the self-inactivating CRISPR/Cas9 editing for applications in the context of neurodegenerative diseases.

Staphylococcus aureus is usually described as an extracellular opportunistic pathogen, infecting a wide range of organs and tissues.However, it also invades and replicates in various phagocytic or nonphagocytic host cells (Hamza & Li, 2014). To be successful as a pathogen, this bacterium needs to adapt to the hostile environment of the host and must acquire imposed nutriments for its survival.Consequently, the staphylococcal genome encodes several transporters for metabolites (sugars, metals, amino acids, etc.), which are

Transcriptional regulation in Chlamydiae is still poorly understood. The absence until recently of genetic tools is the main cause of this gap. We discovered three new potential DNA-associated proteins of Waddlia chondrophila, a Chlamydia-related bacterium, using heparin chromatography coupled to mass spectrometry (Wcw_0377, Wcw_1456, and Wcw_1460). By ChIP-seq analysis, we determined the regulatory landscape of these three proteins and we showed that Wcw_0377 binds all along the genome whereas Wcw_1456 and _1460 possess a wide regulon with a large number of co-regulated genes. Wcw_1456 and Wcw_1460 interact with RpoD (σ66), emerging as potential RpoD regulators. On the other hand, Wcw_0377 is able to reach the host nucleus, where it might interact with eukaryotic histones through its putative chromatin-remodelling SWIB/MDM2 domain.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.