CTRL Enables Gene-Specific RNA Regulation Using CRISPR-Cas7–11

Advancements in synthetic biology have enabled the development
of precision gene expression technologies for comprehensive investigations
of biological and biochemical networks. Here, we describe the development
of a refined and innovative tool, CRISPR-Cas Transgenic Repressible
eLement (CTRL), which utilizes the direct repeat processing activity
of the recently discovered CRISPR-Cas7–11 effector to site-specifically
target synthetic mRNA molecules. We demonstrate that CTRL exhibits
high efficiency, tunable regulation of expression, and gene-specific
repression of mRNA and protein expression. We engineered multiple
permutations of the Cas7–11 effector that differ in their ability
to reduce gene expression, suggesting flexibility for the application
of choice. CTRL is a novel variation on gene repression technology
that exhibits broad applicability across multiple model systems.