repeated DNA sequences decrease the target specificity of the CRISPR-Cas system, and may lead to off-target effects
Explanation:
The CRISPR-Cas system is a versatile and powerful tool for gene editing. This gene-editing tool consists of a single guide RNA (sgRNA) that guides the Cas endonuclease protein to the appropriate genomic locus, where Cas generate a double-strand break in the DNA and thus induces DNA repair either by Non-homologous end joining (NHEJ) or Homologous Recombination (HR) repair pathways. The sgRNA consists of a 17-20 nucleotide sequence which is complementary to the target DNA, this sequence is called crispr RNA (crRNA). The existence of repeated DNA sequences hampers the specificity of the CRISPR-Cas tool because a particular sgRNA is able to guide Cas9 to different genomic loci that have the same (repeated) nucleotide sequence complementary to the crRNA. In consequence, repeated DNA sequences may lead to undesired off-target effects, i.e., unintended cleavage (and therefore unintended mutations) at untargeted genomic sites.