Dose-dependent activation of gene expression is achieved using CRISPR and small molecules that recruit endogenous chromatin machinery

[axolotl]

Dose-dependent activation of gene expression is achieved using CRISPR and small molecules that recruit endogenous chromatin machinery

Abstract

Gene expression can be activated or suppressed using CRISPR­–Cas9 systems. However, tools that enable dose-dependent activation of gene expression without the use of exogenous transcription regulatory proteins are lacking. Here we describe chemical epigenetic modifiers (CEMs) designed to activate the expression of target genes by recruiting components of the endogenous chromatin-activating machinery, eliminating the need for exogenous transcriptional activators. The system has two parts: catalytically inactive Cas9 (dCas9) in complex with FK506-binding protein (FKBP) and a CEM consisting of FK506 linked to a molecule that interacts with cellular epigenetic machinery. We show that CEMs upregulate gene expression at target endogenous loci up to 20-fold or more depending on the gene. We also demonstrate dose-dependent control of transcriptional activation, function across multiple diverse genes, reversibility of CEM activity and specificity of our best-in-class CEM across the genome.

https://www.nature.com/articles/s41587-019-0296-7

[trav]

So the TLDR is; 1. Traditional CRISPR methods involve removed cells into a petri dish or something of the sort. 2. inserting a virus to modify the genes 3. injecting the edited cells back into the body

This is saying that it would skip step #2? So is this just an increase in time efficiency or also an increase in the actual underlying mechanism?

[axolotl]

I will get the full text next week but I believe the previous methods involved larger foreign enzymes such as tet1 that could have had other effects in the cell, whereas this method appears to leverage the cellular machinery to make the adjustments.