Figure 7.

Proposed model for the target expression threshold as a determinant of Cas13-based defense and autoimmunity. Any transcript with extensive complementarity to the crRNA guide flanked by a PFS can be targeted by Cas13. However, the resulting impact on the target gene and the host cell depends on a third factor: target expression. Exceeding a threshold of target expression potentially represents when a sufficient number of Cas13:crRNA complexes are activated to enact widespread RNA cleavage and cellular dormancy. Target expression under the threshold is tolerated and can lead to targeted gene silencing. Target expression above the threshold leads to cytotoxicity for self-targeting and immunity for invader targeting. The exact threshold is target-dependent, likely due to factors that influence guide performance (e.g., local secondary structure, GC content).