A novel advancement of CRISPR technology which allows tuning the magnitude and direction of gene expression levels independently at each individual gene target.
Currently, gene editing systems utilize TALEN proteins, Zn finger proteins and CRISPR technologies based on fusing protein effectors to the dCas9 proteins. CRISPR-Cas systems are faster and simpler than the others and are quickly replacing other gene editing systems as the gold standard. However, this new version of the CRISPR-dCas system is tailored toward simultaneous tunable directional control of gene expression. Most simply, this approach provides a straightforward and general method to switch on one set of genes while switching off another set.
Additional advantages of this invention are:
- Tuning the magnitude and direction of gene expression levels independently at each individual gene target
- Arbitrary genes can be targeted by engineering a small guide RNA (sgRNA) with the appropriate complementary sequence of bases
The scientists at UCSF have developed a system that represents an advance over prior CRISPR transcriptional systems. This system can be used to differentially control the expression of multiple genes simultaneously in eukaryotic cells including yeast, mammalian and plant cells. The CRISPR complex is targeted to specific sites in the genome with a small guide RNA (sgRNA) and a deactivated version of the nuclease Cas9 (dCas9). In this system, the sgRNA has been engineered to include RNA-motifs that serve as modular recruitment sites for effector proteins, which can be activators or repressors. Each sgRNA encodes both the gene target and the effector function to be recruited, unlike prior systems in which the effector domain is directly fused to the dCas9 protein.
1) Metabolic engineering (industrial microbes or cell lines)
2) Regenerative medicine/Cell fate reprogramming (mammalian cells)
3) Disease cell engineering (mammalian cells)
4) Plant engineering (plants)
To develop and commercialize this technology as a genome engineering system which could benefit tool-based genomic providers, genomic services providers, providers of gene expression systems.
|United States Of America||Published Application||20170233762||08/17/2017||2014-144|