Preclinical evaluation demonstrates that nebulized A20FMDV2-siRNA targeting ST6GAL1 reduces viral load and inflammation in lungs, suggesting a viable host-directed influenza prophylaxis.
Key Points
To evaluate whether aerosol delivery of a peptide-conjugated siRNA targeting the host gene ST6GAL1 can safely and durably prevent influenza A virus infection.
Engineered chemically modified St6gal1 siRNA conjugated to the targeting peptide A20FMDV2 and delivered it to respiratory tissue using nebulization.
Evaluated metabolic stability and duration of pulmonary St6gal1 gene silencing following a single dose.
Assessed viral nucleoprotein levels, infectious titers, neuraminidase activity, inflammation, and systemic toxicity following influenza A viral challenge.
A single nebulized dose resisted enzymatic breakdown and maintained pulmonary St6gal1 silencing for at least 14 days.
Prophylactic conjugate delivery delayed viral nucleoprotein RNA and protein accumulation while markedly lowering infectious titers, neuraminidase activity, and pulmonary inflammatory markers.
Nebulized administration produced no evident acute histopathological damage, hematological changes, or serum biochemical toxicity.