# CRISPR-Cas Systems: Prospects for Use in Medicine
###### Abstract  
CRISPR-Cas systems, widespread in bacteria and archaea, are mainly responsible for adaptive cellular immunity against exogenous DNA (plasmid and phage). However, the latest research shows their involvement in other functions, such as gene expression regulation, DNA repair and virulence. In recent years, they have undergone intensive research as convenient tools for genomic editing, with Cas9 being the most commonly used nuclease. Gene editing may be of interest in biotechnology, medicine (treatment of inherited disorders, cancer, etc.), and in the development of model systems for various genetic diseases. The dCas9 system, based on a modified Cas9 devoid of nuclease activity, called CRISPR, is widely used to control gene expression in bacteria for new drug biotargets validation and is also promising for therapy of genetic diseases. In addition to direct use for genomic editing in medicine, CRISPR-Cas can also be used in diagnostics, for microorganisms' genotyping, controlling the spread of drug resistance, or even directly as \"smart\" antibiotics. This review focuses on the main applications of CRISPR-Cas in medicine, and challenges and perspectives of these approaches.  
CRISPR-Cas; genome editing; gene therapy; drug resistance +
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since the DR set usually differed within one species. It was only in the 2000s when the role of CRISPR-Cas systems in the bacterial immunity was described [5; 6].  
These systems were well studied subsequently, with other functions, such as gene expression regulation, DNA repair, and even indirect participation in the process of host infection, described for them aside from providing adaptive immune response [7; 8; 9; 10; 11; 12]. CRISPR-Cas systems evolve rather slowly, especially if compared to constantly changing viruses and mobile genetic elements, therefore, having only one function could have been shown to be evolutionarily disadvantageous [13]. Thus, in _Pseudomonas aeruginosa_, these systems have been shown to participate in biofilm formation and virulence [14]. In _Myxococcus xanthus_, Cas proteins are involved in the regulation of the fruiting body formation [15]. For _E. coli_, the involvement of CRISPR-Cas systems in the processes of DNA repair through the interaction of the Cas1 (YgbT) protein with the _recB_, _recC_, and _ruvB_ genes, which are key components of the repair systems, has been demonstrated [8]. These systems can also be involved in virulence. In 2013, the involvement of CRISPR-Cas in post-transcriptional control in _Francisella novicida_ was established, in which the gene encoding a virulence factor (lipoprotein that induces an inflammatory response in the host) is regulated by the Cas protein (namely Cas9) and CRISPR-associated small RNAs [16]. It is assumed that in this case Cas9 targets endogenous mRNA, rather than DNA. Currently, the relationship between CRISPR-Cas systems and the ability of bacterial strains to exhibit increased virulence or even drug resistance has been shown in a number of studies [17].  
Although genome editing (including the medical field) is the most important application of CRISPR-Cas, it is not the only one. The use of these systems in biotechnology for altering metabolic pathways of various prokaryotic and eukaryotic organisms used in industry may be also promising. In addition, CRISPR-Cas can be a tool for bacterial studies, including pathogenic ones. These studies include, but are not limited to: genotyping and epidemiological studies, studying the role of individual genes in the pathogenesis and survival of bacteria (including search for new drugs' biotargets), and for targeted killing of certain bacterial strains, including drug resistant ones.