CRISPRCa

CRISPRCa is a term used to describe a conceptual class of systems that aim to couple CRISPR-based genome regulation with intracellular calcium signaling to achieve calcium-dependent control of gene expression. The idea envisions using calcium dynamics as a trigger to activate or repress transcription or to influence genome editing events.

Conceptually, CRISPRCa designs may employ calcium-responsive elements to gate CRISPR activity. Possible approaches include fusing a dead or catalytically active Cas9 (dCas9) effector to calcium-binding domains such as calmodulin, so that increases in intracellular Ca2+ induce conformational changes that recruit transcriptional activators or repressors to target promoters. Alternatively, calcium-responsive promoters or riboswitches could regulate the expression of sgRNA or Cas proteins, creating a system that opens or closes in response to calcium thresholds. Some designs may also use calcium-activated transcription factors that translocate to the nucleus and recruit CRISPR machinery to specific genomic loci.

Implementation strategies are diverse and remain largely theoretical. Researchers may combine inducible degron systems, protease-cleavable linkers, or other calcium-sensitive switching mechanisms to achieve tighter control and reduce basal activity. Delivering such components in a coordinated, tissue-specific, and clinically safe manner represents a major technical challenge.

Applications envisioned include studies of neuronal and cardiac physiology, where calcium dynamics are central, as well as broader synthetic biology contexts where cellular activity governs gene regulation. Status-wise, CRISPRCa remains largely hypothetical with limited experimental demonstration and no standardized platform. If validated, it could add a physiologically gated layer to genome engineering beyond existing CRISPRa/CRISPRi approaches.