CRISPR Diagnostics Meets Genome Editing: Shared Enzymes, Shared Mechanisms

CRISPR systems sit at the core of modern genome engineering, yet the same enzymes and design principles that enable precise genome editing also underpin a fast-moving wave of CRISPR-based diagnostics. This Research Topic focuses on the shared molecular foundations of these two application spaces—programmable nucleic-acid recognition by guide RNAs, sequence-context constraints (e.g., PAM/PFS requirements), conformational activation, cleavage chemistry, and specificity–efficiency tradeoffs. By treating diagnostics and editing as two operating modes of a common biochemical toolkit, the collection aims to connect mechanistic insights across fields and accelerate the development of more predictable, tunable, and safe CRISPR technologies.A central premise is that many questions traditionally framed as “editing problems” are equally “detection problems,” and vice versa. Mismatch tolerance, kinetic control of target interrogation, off-target binding landscapes, guide architecture, nuclease engineering, and reaction environment (temperature, ionic strength, cofactors, crowding) influence editing outcomes in cells and detection performance in vitro. Diagnostic platforms—where enzyme kinetics and specificity can be measured with high quantitative control—can serve as powerful testbeds for understanding nuclease activation pathways, catalytic switching, and sequence discrimination, generating models and design rules that translate back into editing. Conversely, innovations from genome editing—high-fidelity variants, expanded targeting scope, programmable nicking, catalytically dead binders, base/prime editing-derived modules, and delivery-inspired stabilization strategies—can be repurposed to build assays that are more sensitive, multiplexable, and resilient to sequence variation.This Research Topic welcomes contributions that advance mechanistic understanding and tool development at the intersection of CRISPR diagnostics and genome editing, including but not limited to: comparative studies of Cas9/Cas12/Cas13 (and emerging or engineered effectors) that unify specificity metrics across cellular and cell-free contexts; enzyme and guide engineering to tune activation thresholds, mismatch discrimination, and catalytic outputs; strategies that exploit or suppress collateral activity; amplification-free and one-pot detection chemistries informed by editing-grade protein engineering; computational and biophysical models that predict targeting outcomes across environments; and standardized benchmarking approaches for sensitivity, specificity, and off-target assessment. We also encourage perspectives that outline best practices and conceptual frameworks to harmonize terminology and measurement across communities.By emphasizing shared enzymes and shared mechanisms, this collection aims to bridge communities that often publish separately, creating a coherent mechanistic picture of CRISPR function that supports both next-generation genome editing tools and robust CRISPR-enabled diagnostics. The outcome will be a resource for researchers designing new effectors, improving specificity, and translating CRISPR technologies toward biological discovery and clinical impact. Topic editors: KANISHT BATRA, Gaurav Charaya Source: https://www.frontiersin.org/research-topics/78237/crispr-diagnostics-meets-genome-editing-shared-enzymes-shared-mechanisms