Exploring ALS (Acetolactate synthase) gene as a target for herbicide resistance through CRISPR/Cas mediated genome editing

The increasing global population, combined with escalating climate change, has necessitated the adoption of innovative agricultural practices to ensure sustainable food production. Traditional crop cultivation system relies on conventional weed management practices that are labour and resource intensive. To address this challenge, the development of herbicide-resistant (HR) crops has emerged as a critical solution. CRISPR/Cas-based genome editing has revolutionized HR crop development, offering precision and efficiency over conventional breeding and transgenic approaches. The acetolactate synthase (ALS) gene, which is essential for biosynthesis of branched-chain amino acids (BCAAs) such as leucine, isoleucine and valine, serves as a key target for ALS-inhibiting herbicides to control broad spectrum of weed species. Notably, several weed species were identified with natural mutations in ALS gene that confers strong level of resistance to different ALS-inhibiting herbicides. Advanced genome editing technologies like CRISPR/Cas9, CRISPR/Cas mediated base editing (BE) and prime editing (PE) have been successfully utilized to mimic these natural mutations or introduce novel mutations in ALS gene, thereby creating heritable herbicide resistance in various crops. In this review, we summarize the remarkable achievements reported so far in the development of herbicide-resistant crops specifically by targeting the ALS gene using CRISPR/Cas genome editing approach. Furthermore, we propose forward-looking perspectives on integrating multiplex gene editing and gene stacking. The synergy between CRISPR (Clustered Regularly Interspaced Palindromic Repeat) technology and advanced phenotyping platforms holds significant promise for next generation of climate-resilient herbicide resistance crop varieties. These insights offer a valuable roadmap for researchers to design tailored, sustainable weed management strategies and accelerate the global transition towards precision agriculture.