Emersion of persistent Staphylococcus aureus requires original research and developmental planning. Repression of virulence genes might be a committed therapeutic approach in this regard. Gene-quenching with short interfering RNA (siRNA) is considered an adequate factor strategy. The study demonstrates the potential of siRNA to effectively silence key genes involved in MRSA virulence and antibiotic resistance. As stated, the microbiological routine is approved to confirm bacterial isolates. TD tests were optimized for persistency affirmation. We devised 21-bp siRNA duplexes against staphylococcal protease. RT-PCR was employed to measure levels of agrII and MecA mRNA before and after siRNA treatment. The efficacy of siRNA was determined by using phenotypic, genotypic, and statistical protocols to confirm the results of the designed laboratory experiment for QS factor quenching. Results showed that siRNA targeting agrII significantly reduced the mRNA levels compared to controls. This reduction in agrII expression correlated with a decrease in quorum sensing activity, agrII silencing led to a marked decrease in the production of staphyloprotease, as appeared on the modified culture media for protease testing. This indicates that agrII is crucial for regulating virulence factors, its diminished virulence, making the infection less severe and easier to manage by the immune system. 
In conclusion, outcomes revealed that siRNA can effectively silence key genes involved in S. aureus virulence and antibiotic resistance. Targeting agrII disrupts quorum sensing and reduces staphyloprotease production, potentially mitigating the pathogenicity of this bacterium. Targeting protease by siRNA presents an incoming delineation for curing persistent methicillin-resistant Staphylococcus aureus infections.