Clinical bottom line
Novel gene editing therapies designed to confer inherited resistance to infectious diseases represent an emerging frontier in infectious disease management. While these therapies hold promise for reducing susceptibility to specific pathogens, their impact on infection risk profiles and clinical management remains incompletely characterized. Current evidence is largely preclinical or extrapolated from analogous biologic and cellular therapies, underscoring the need for cautious interpretation. Infectious disease clinicians should be aware of potential altered immune responses, atypical infection presentations, and the necessity for tailored monitoring strategies in patients receiving such gene editing interventions.
What the evidence shows
Gene editing approaches, including CRISPR-Cas9 and related technologies, are being developed to correct or modify host genes implicated in susceptibility to infectious agents. Although much of the clinical experience is in inherited retinal dystrophies (Stieger et al., 2017; Chirco et al., 2023), the principles are increasingly applied to infectious disease resistance, such as editing CCR5 to reduce HIV entry or modifying genes involved in mycobacterial susceptibility.
Direct clinical data on infection risks following gene editing therapies for infectious disease resistance are sparse. However, analogous insights can be drawn from experiences with novel biologic and cellular therapies. For example, patients receiving anti-tumor necrosis factor (TNF) agents and other biologics show increased risks of serious infections, including mycobacterial diseases (Winthrop et al., 2008; Pediatric Infectious Disease Journal, 2008). Similarly, hematopoietic cell transplant recipients and patients undergoing cellular therapies face complex infectious risks due to immune modulation (Garner et al., 2023). These data highlight that immune perturbations, even when targeted, can predispose to opportunistic or atypical infections.
Gene editing therapies may alter immune surveillance or inflammatory pathways in ways that are not yet fully understood, potentially leading to unexpected infectious complications. For instance, complement inhibition with eculizumab has been associated with disseminated gonococcal infections (Pediatric Infectious Disease Journal, 2019), illustrating how targeted immune interventions can shift infection susceptibility.
Central nervous system infections have also been reported in patients receiving cancer therapies that modulate immunity (Pruitt et al., 2017), reinforcing the need for vigilance in patients undergoing novel immunomodulatory interventions.
Caveats and uncertainty
The field of gene editing for infectious disease resistance is nascent, and robust clinical outcome data on infection risks are lacking. Most evidence is extrapolated from other immunomodulatory therapies rather than direct studies of gene editing interventions. The heterogeneity of gene targets, editing platforms, and patient populations complicates risk assessment.
Long-term effects on immune function and infection susceptibility remain unknown. Off-target gene effects or unintended immune consequences could alter infection risk profiles unpredictably. Additionally, the durability of gene edits and their impact on host-pathogen interactions over time require further study.
Current clinical guidelines do not yet address infection monitoring or prophylaxis specifically for patients receiving gene editing therapies for infectious disease resistance. Thus, infectious disease clinicians must integrate evolving evidence with individualized risk assessment.
How this may change practice
Clinicians should maintain a high index of suspicion for unusual or opportunistic infections in patients treated with gene editing therapies, especially as these become more widely used. Pre-treatment infectious risk assessment and baseline screening remain essential.
Close collaboration with gene therapy and immunology specialists is recommended to tailor infection prevention strategies, including vaccination, antimicrobial prophylaxis, and monitoring protocols. Awareness of potential atypical infection presentations or immune dysregulation is critical.
As clinical data accumulate, infectious disease specialists will need to update practice guidelines to incorporate gene editing therapy–specific recommendations. Participation in registries and post-marketing surveillance will be important to elucidate infection risks and optimize management.