Epstein-Barr virus (EBV) infects over 90% of people worldwide and can drive B cell lymphomas in a fraction of infected individuals. Latent Membrane Protein 1 (LMP1) is the primary oncogene of EBV and is known to affect host cell microRNAs (miRs); small RNAs that interfere with translation of mRNA to protein. One of the miRs that LMP1 upregulates is miR-155, an oncogenic miR highly implicated in B cell transformation. miR-155 likely transforms B cells by targeting mRNAs encoding multiple known tumor suppressors, transcription factors, and cell cycle regulators. One such miR-155 gene target is FOXO3, which encodes a known tumor suppressor, FOXO3a. A new mechanism by which LMP1 activation leads to the upregulation of miR-155 and the downregulation of FOXO3a, the protein product of miR155 target FOXO3, was recently identified (Hatton et al, 2019). Researchers identified PI3K p110α as an intermediate activator in the pathway by which LMP1 upregulates miR-155 and downregulates FOXO3a with the use of small molecule inhibitors (Hatton et al., 2019). This study sought to validate these results using small-interfering RNAs (siRNAs) targeting PI3KCA, the transcript that encodes PI3K p110α. We first had to optimize the conditions for siRNA transfection and knockdown of proteins encoded by miR155 target transcripts. We found that viability was optimal when complete RPMI media was added back after 72 hours of incubation. Transfection efficiency was optimal when cells were incubated with 5 μM siRNA in Accell media with 0% FBS. We were unable to confirm knockdown by qPCR due to unreliable RNA isolation. However, we were able to visualize partial knockdown of GAPDH, our endogenous positive control, via Western blot after implementing our optimal conditions with an extended incubation of 120 hours and seeding the incubation wells with 0.5 x 106 cells/mL. This optimized system of siRNA delivery into BL41 cells can be utilized to validate that PI3K p110α is activated by LMP1 and is important to the upregulation of miR155 by LMP1 and subsequent downregulation of FOXO3a. siRNA transfection of BL41 cells can further be utilized in further study of transformation of host B cells by LMP1.