TY - JOUR T1 - Gene Drives beyond Proof of Concept: A Critical Review of Molecular Performance, Evolutionary Escape, Ecological Uncertainty, and Release Governance A1 - David Thompson A1 - Sarah Mitchell A1 - Rachel Adams A1 - James Brown A1 - Michael Lee JF - Entomology and Applied Science Letters JO - Entomol Appl Sci Lett SN - 2349-2864 Y1 - 2026 VL - 13 IS - 1 DO - 10.51847/7wjrQgb8h2 SP - 48 EP - 60 N2 - Gene drives offer a powerful means of altering inheritance to suppress harmful insect populations or introduce traits intended to reduce pathogen transmission. Their development has nevertheless advanced faster than the evidence needed to determine whether molecular success can be translated into durable, spatially predictable, controllable, and publicly legitimate environmental action. This critical review examines the evidentiary gap between proof-of-concept performance and defensible release decision-making. It integrates comparative evidence concerning gene-drive architectures and intended population effects, molecular efficiency and inheritance performance, resistance-allele formation and evolutionary escape, ecological uncertainty and spatial spread, containment and reversal, monitoring, and release governance. The evidence supports a central distinction between demonstrating an inheritance mechanism and establishing readiness for environmental use. High transmission or population suppression in contained systems may establish technical plausibility, but it does not demonstrate stable population modification, predictable movement through heterogeneous landscapes, ecological reversibility, or acceptable release conditions. Results remain contingent on construct architecture, target-site conservation, expression timing, repair outcomes, fitness costs, genetic background, demographic structure, migration, environmental variability, and the quality of monitoring and governance arrangements. The principal limitations of the evidence base are its concentration in laboratory and cage systems, incomplete representation of wild genetic and ecological heterogeneity, short evolutionary observation periods, and limited integration between technical studies and decision processes. Responsible progression therefore requires claim-specific evidence gates rather than a single readiness score. Molecular performance, evolutionary durability, ecological prediction, containment credibility, monitoring capacity, legitimacy, and formal authorization should be evaluated as separate but connected requirements, with explicit uncertainty, failure pathways, and return-to-design conditions. UR - https://easletters.com/article/gene-drives-beyond-proof-of-concept-a-critical-review-of-molecular-performance-evolutionary-escape-zsrqc1csflumevv ER -