Applications of the CRISPR-Cas9 system in kidney research

Abstract

The recently discovered clustered regularly interspaced short palindromic repeat (CRISPR)-CRISPR-associated protein 9 (Cas9) is an RNA-guided DNA nuclease, and has been harnessed for the development of simple, efficient, and relatively inexpensive technologies to precisely manipulate the genomic information in virtually all cell types and organisms. The CRIPSR-Cas9 systems have already been effectively used to disrupt multiple genes simultaneously, create conditional alleles, and generate reporter proteins, even in vivo. The ability of Cas9 to target a specific genomic region has also been exploited for various applications, such as transcriptional regulation, epigenetic control, and chromosome labeling. Here we first describe the molecular mechanism of the RNA-guided DNA targeting by the CRISPR-Cas9 system and then outline the current applications of this system as a genome-editing tool in mice and other species, to better model and study human diseases. We also discuss the practical and potential uses of the CRISPR-Cas9 system in kidney research and highlight the further applications of this technology beyond genome editing. Undoubtedly, the CRISPR-Cas9 system holds enormous potential for revolutionizing and accelerating kidney research and therapeutic applications in the future.

Targeting the IGF1R Pathway in Breast Cancer Using Antisense lncRNA-Mediated Promoter cis Competition

“…CRISPR-Cas9 technology has been employed as a simple, efficient, and relatively inexpensive technology to precisely edit genes for various applications, including transcriptional regulation, epigenetic control, and chromosome translocation. 27 , 28 , 29 Recently, this editing system has been harnessed to correct disease genes in human embryo genomes. 30 , 31 , 32 By tethering the C terminus of the catalytically inactive dCas9 to three epigenetic suppressor domains, we found that the synthetic dCas9 epi-suppressor gRNAs induced significant decreases in the transcription activity of the GRN target gene promoter in Hep3B hepatoma cells.…”

Generating mouse models for biomedical research: technological advances

“…The RNA-guided Cas9 nuclease system has also become a powerful tool for both forward and reverse genetics (Gurumurthy et al, 2016c), generating models that are relevant for many diseases, including cancer (Platt et al, 2014). Several recent review articles discuss the Cas9-nuclease-generated mouse models for different disease types, including for cancer (Mou et al, 2015; Roper et al, 2017), cardiovascular diseases (Miano et al, 2016), neurodegenerative diseases (Yang et al, 2016) and kidney diseases (Higashijima et al, 2017). In addition, several reviews on Cas9-nuclease-generated models have been recently published that discuss their human disease relevance (Dow, 2015; Tschaharganeh et al, 2016; Cai et al, 2016; Yang et al, 2016; Birling et al, 2017).…”

CRISPR/Cas9-related technologies in liver diseases: from feasibility to future diversity

“…It was reported that the CRISPR/Cas9 system can be used for genome editing in mammalian cells. The following studies found that the CRISPR/ Cas9 system can be utilized to generate KO mice efficiently [18]. At this point, CRISPR/Cas9 ultimately came to the world as genetic engineering technology.…”