CRISPR-ERA for Switching Off (Onco) Genes

Abstract

Genome-editing nucleases like the popular CRISPR/Cas9 enable the generation of knock- out cell lines and null zygotes by inducing site-specific double-stranded breaks (DSBs) within a genome. In most cases, when a DNA template is not present, the DSB is repaired by nonhomologous end joining (NHEJ), resulting in small nucleotide insertions or dele tions that can be used to construct knockout alleles. However, for several reasons, these mutations do not produce the desired null result in all cases, instead generating a similar protein with functional activity. This undesirable effect could limit the therapeutic effi - ciency of gene therapy strategies focused on abrogating oncogene expression by CRISPR/ Cas9 and should be taken into account. This chapter reviews the irruption of CRISPR technology for gene silencing and its application in gene therapy.