CRISPR-based therapeutics to combat respiratory viral infections

Respiratory viral infections remain a major global health challenge, underscored by seasonal influenza, respiratory syncytial virus (RSV), and the COVID-19 pandemic. Although vaccines and antiviral drugs are central to control strategies, their effectiveness can be limited by viral evolution, resistance, and delayed development. CRISPR-based antivirals have emerged as a programmable approach to directly target viral genomes or host factors required for infection. This review summarizes current CRISPR strategies for respiratory viruses, focusing on RNA-targeting systems such as Cas13 and DNA-targeting approaches, including Cas9 and Cas12. We synthesize evidence from preclinical studies in cell culture, primary human airway models, and animal lungs, highlighting how guide design, multiplex targeting, and conserved viral regions can limit viral escape. We also discuss key translational challenges, including pulmonary delivery, biodistribution, off-target profiling, immune responses, and regulatory considerations. Finally, we outline future directions, including integration with antimicrobial peptides, rapid viral genotyping, and combination therapies. Together, this review provides a practical assessment of what CRISPR antivirals can realistically offer for respiratory viral infections and identifies the critical steps needed to advance these approaches toward clinical use.