Decoding heavy metal tolerance in rice: Nucleic acid-based technologies shaping global food security

Global rice production is critically threatened by heavy metal contamination, particularly cadmium (Cd) and arsenic (As), which compromises yield, diminishes grain nutritional quality, and exposes billions of consumers to nephrotoxic and carcinogenic risks. Conventional remediation strategies (soil amendments, water management, phytoremediation) are prohibitively expensive, temporally protracted, and fundamentally reactive, while conventional breeding is constrained by linkage drag, polygenic trait architecture, and absence of natural alleles that restrict toxic metal uptake from essential mineral nutrition. This review critically examines how nucleic acid-based technologies have fundamentally reconfigured the discovery-to-deployment pipeline for heavy metal tolerance in rice. We trace the progression from early QTL mapping and positional cloning of transporters through population-scale GWAS and pan-genomics, which have resolved the full allelic series at these loci, to contemporary CRISPR-mediated genome editing, that generated transgene-free, field-validated low-accumulating lines. Transcriptomic, epigenomic, and metagenomic tools have further illuminated the dynamic stress response, non-coding regulatory networks, and rhizosphere microbiome contributions to metal exclusion. Translational case studies including Japan's marker-assisted deployment of OsHMA3 for Cd mitigation and South Asia's development of OsLsi2-edited low-As lines demonstrate that these technologies are not merely academic instruments but operational solutions. However, specificity-versus-essentiality dilemma, multi-metal antagonism (Cd/As redox conflict), and profound regulatory divergence (SDN-1 exemption in the Americas, Japan, and India versus GMO classification in the EU) remain formidable barriers. We conclude that nucleic acid technologies constitute the cornerstone of a second Green Revolution focused on grain quality and safety, contingent upon sustained investment in synthetic biology, digital integration, and internationally harmonized governance frameworks.