CRISPR-Cas is an adaptive immune system of prokaryotes (bacteria and archaea). Apart from protecting its host against invading viruses, also alternative biological functions of CRISPR-Cas have been revealed. The first mechanistic details of interference by a CRISPR-Cas system were obtained by molecular analysis of the Escherichia coli Cascade system (Class-1). These initial fundamental insights of the RNA-guided DNA interference mechanism of CRISPR-Cas have provided the basis for a broad spectrum of genome editing applications, initially for the analogous DNA-targeting Class-2 systems: Cas9 and Cas12. Recently, however, also applications of the Cascade/crRNA complex have been developed, either as stand-alone complex (silencing of gene expression), or in combination with the Cas3 nuclease (large genome deletions), with transposons (large genome insertions), and with the FokI-nuclease domain (precision engineering). Moreover, Cascade-like CRISPR-Cas systems have recently been repurposed as diagnostics tool, allowing for sensitive detection of target nucleic acids. Overall, it is concluded that the impact of CRISPR-Cas is unprecedented, from intriguing host-pathogen biology to spectacular applications in the fields of genome editing (human gene therapy) and diagnostics (COVID-19 monitoring) !
Join Prof. Dr. John van der Oost from Wageningen University and discover
- How have CRISPR-Cas systems been discovered, and what explains their diversity
- What mechanisms are used by CRISPR-Cas systems
- What CRISPR-Cas applications have been developed
John Van der Oost is considered a pioneer of the "CRISPR revolution" for his fundamental work on unravelling the mechanism of CRISPR-based immunity in bacteria, paving the way for developing CRISPR-mediated genome editing. In a seminal 2008 paper "Small CRISPR RNAs guide antiviral defense in prokaryotes", Van der Oost and co-workers were the first to demonstrate that CRISPR-Cas system uses an RNA-guided mechanism to specifically target DNA. Moreover, they successfully transplanted the system to another host bacterium, and demonstrated that an appropriately designed CRISPR allowed for specific targeting of any DNA sequence. This first example of programmable gene editing, subsequently developed for the CRISPR-Cas9 system that has been been further used by many research groups for applications ranging from fundamental protein research to revolutionary treatments for diseases including sickle cell anemia, cystic fibrosis, Huntington's disease, and HIV. The CRISPR-Cas research is considered as one of the most significant discoveries in the history of biology.