Fig. (4).

Meganucleases as antiviral agents. Pathways by which viral sequences belonging either to essential genes or regulatory regions can be inactivated are shown. Gene inactivation can result from small insertions/deletions that introduce lethal mutations in the viral genome by error-prone non-homologous recombination (panel a). Large deletions can be introduced by DNA cleavage and repair when using two different meganucleases targeting the same viral genome at different positions (panel b), or by rejoining DNA ends when cleavage occurs in a repeated region of the viral genome (panel c). Alternatively, when cleavage occurs between two direct repeats (e.g.: the LTR retroviral sequences), deletion of the intervening sequences can be generated by tandem repeat recombination (SSA, panels a and b). While the pathways depicted in panels a-c are valid for integrated as well as episomal viruses, the latter can also be targeted via the degradation and clearance of the viral genome upon DNA cleavage (panel d).