CRISPR/Cas-Driven Biofortification: A New Frontier in Combating Hidden Hunger

Micronutrient malnutrition (“hidden hunger”) remains a pervasive global challenge, undermining growth, cognitive development, and health, particularly in vulnerable populations. Biofortification of staple crops offers a sustainable pathway to address these deficiencies, and the emergence of CRISPR/Cas genome editing has transformed this strategy by enabling precise and heritable enhancement of crop nutritional traits. This review summarizes recent advances in CRISPR/Cas-mediated biofortification across major crops such as rice, wheat, maize, and cassava, as well as underutilized species. It highlights the roles of key CRISPR platforms including Cas9, Cas12a, base editing, and prime editing in increasing essential micronutrients such as iron, zinc, provitamin A, folate, and omega-3 fatty acids. In addition to technical advancements, the review examines the biological and translational challenges that shape the effectiveness of CRISPR-based biofortification. These include off-target modifications, the complexity of polygenic nutritional traits, epigenetic influences on gene expression, and inconsistencies in regulatory frameworks across regions. It also addresses practical limitations such as the scarcity of multi-environment field data and the underrepresentation of orphan crops, which are often critical for regional food security. Looking forward, the review outlines emerging strategies to enhance the impact and scalability of CRISPR/Cas applications. These include multiplex genome editing to simultaneously target multiple pathways, integration with conventional breeding and genomic selection, and the need for multi-location and multi-generational validation. Emphasis is also placed on interdisciplinary collaboration spanning genomics, agronomy, nutrition, and socioeconomics to ensure equitable and effective deployment. Collectively, this review underscores the transformative potential of CRISPR/Cas-mediated biofortification in combating micronutrient deficiencies, strengthening food systems, and advancing progress toward Sustainable Development Goal 2 (Zero Hunger).