Chronic feline herpesvirus-1 (FHV-1) infection mainly affects the eyes; repeated recrudescence can lead to blindness. Small interfering RNAs (siRNAs) can target essential genes of FHV-1. Ideally, a siRNA preparation would be delivered topically to the cornea, as this would allow for higher concentrations of siRNAs in the infected cells. Challenges to topical delivery include the hydrodynamics of blinking and tear flow, which quickly remove siRNAs from the corneal surface.
Agents delivering siRNAs into feline corneal cells, toxicity of the delivery agents, and functionality of anti-FHV-1–specific siRNA combinations were evaluated. Despite rapid transfection of siRNAs into corneal cells in vitro, none of the agents tested in vivo were effective in delivering siRNAs into the corneal cells. It is likely the siRNA solutions were diluted and removed too rapidly to be effective because of tear film turnover. Although multiple applications of the siRNA solutions may enhance delivery, this might negatively affect compliance. Further studies to identify ways to increase contact time between siRNAs and corneal cells (eg, use of ointments for delivery) are needed.
Evaluation of delivery agents used for introduction of small interfering RNAs into feline corneal cells. Wilkes RP, Ward DA, Newkirk KM, et al. AM J Vet Res 74:243-247, 2013.