Perspectives of RNAi, CUAD and CRISPR/Cas as Innovative Antisense Technologies for Insect Pest Control: From Discovery to Practice

Pest management has entered a new era with the emergence of three innovative antisense technologies: RNAi, CUAD, and CRISPR/Cas. These technologies, which operate through sequence-specific nucleic acid duplex formation and guided nuclease activity, offer unprecedented potential for targeted pest control. While RNA-guided systems such as RNAi and CRISPR/Cas were initially discovered in non-insect models as fundamental biological mechanisms (primarily in antiviral defense), the DNA-guided CUAD system was first identified in insect pests as a practical tool for pest control, while its broader role in ribosomal RNA (rRNA) biogenesis only recently recognized. These surprising discoveries have unveiled an entirely new dimension of gene regulation, with profound implications for sustainable pest management. Despite certain similarities of these technologies, RNAi, CUAD, and CRISPR/Cas differ in their mode of action, specificity, and applicability. No single approach provides a universal solution for all insect pests; instead, each is likely to be most effective against specific pest groups. Moreover, these technologies enable the rapid adaptation of pest management strategies by countering target-site resistance, ensuring long-term efficacy. This review provides a critical synthesis of the unique advantages and limitations of each antisense technology, highlighting their complementary roles in eco-friendly, nucleic acid-guided insect pest control. By bridging fundamental discoveries with applied research, we offer new perspectives on their practical implementation, underscoring the urgent need for their integration into modern pest management strategies.