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Transient co-expression of engineered transcriptional repressors (ETRs) allows for 
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BigField GEG Tech's insight:
The authors analyzed the genome-wide effects of TALE- and CRISPR-based transcriptional activators in human cells. Their results show that these transcription factors are highly specific in both DNA-binding and gene regulation, and are able to open targeted regions of closed chromatin independent of gene activation. Collectively, these results underscore the potential for these technologies to make precise changes to gene expression for gene and cell therapies or fundamental studies of gene function.
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BigField GEG Tech's insight:
The authors report their improvements made to the existing SB vector system and present two new vector types for robust constitutive or inducible expression of any gene of interest.
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BigField GEG Tech's insight:
In this work, the authors used the ΦC31 integrase system to study the effects of the continuous exposure of exogenous sclerostin on bone. They injected Sost-attB plasmid with ΦC31 integrase plasmid into the mouse tail vein using a hydrodynamic-based method. Sclerostin was expressed in the hepatocytes, secreted into the blood flow, and maintained at high concentrations in the mice injected. These mice showed trabecular bone loss on micro-CT analysis. These findings may help to further ascertain the effects of sclerostin introduced exogenously on the skeleton.
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BigField GEG Tech's insight:
Off-target effects are a critical issue for genome editing and transcriptome modulation. Here the authors review the current status on the target specificity of the CRISPR-Cas9 system.
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BigField GEG Tech's insight:
A new study reports an extension of the CRISPR (clustered regularly interspaced short palindromic repeat) technology that enables the simultaneous, tunable and directional control of expression of multiple genes. At its most basic, this method allows switching on one set of genes while switching off another set to generate synthetic multigene transcriptional programmes that can be induced to, for example, 'rewire' cell fates or engineer metabolic pathways. To achieve flexible locus-specific transcriptional programming at multiple genes simultaneously, the researchers took advantage of features inherent to RNA, such as its modularity and programmability: RNA has previously been shown to form scaffolds that link DNA binding through base pairing to protein recruitment and the assembly of functional protein complexes.
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Here, the scientists repurpose the endogenous retroviruses’ silencing machinery of embryonic stem cells to stably silence three highly expressed genes in somatic cells by epigenetics. This was achieved by transiently expressing combinations of engineered transcriptional repressors that bind to and synergize at the target locus to instruct repressive histone marks and de novo DNA methylation, thus ensuring long-term memory of the repressive epigenetic state. They demonstrate the portability of this technology by multiplex gene silencing, adopting different DNA binding platforms and interrogating thousands of genomic loci in different cell types, including primary T lymphocytes. Targeted epigenome editing might have broad application in research and medicine.