The results from our study led to formulation of PI3K small molecule inhibitors selection guidelines for conjugation to RNA nanoparticles: 1) conjugation drug candidates must demonstrate high activity in the nM range; 2) broad sensitivity of cancer cells to a select agent; 3) long duration of pathway inhibition; and 4) drug stability in extracellular space in vivo. The gene discussed is PIK3CA; the disease is cancer.