The adaptive bacterial immune system CRISPR-Cas and its therapeutic potential.

The bacterial CRISPR-Cas-system is an adaptive and inheritable immune system for the defense against invasive genetic elements such as viral DNA or plasmids. CRISPR-Cas immunity acts by integrating short sequences of non-self DNA in the cell’s CRISPR locus which allows the cell to recognize, to remember and to destroy the invasive element. In the last years the type-II-system CRISPR-Cas9 was developed as a powerful and universal tool for the sequence-specific modification of the genome also known as genome editing. Type-II-systems rely solely on one single protein, Cas9, and a non-coding, trans-activating RNA that leads the Cas9 protein to its target DNA. The RNA-guided molecular scissor Cas9 is predestinated to correct mutated genes in line with a gene therapy and to heal chronic diseases like HIV infections or virus-induced forms of cancer via deleting viral DNA that is integrated as a provirus in the host’s genome. In addition, catalytically inactive Cas9 variants (dCas9) fused to effector domains can be used to specifically tag genome sections, regulate gene expression and modify epigenetic markers.