Therapeutic targeting of KRAS mutation-driven tumorigenesis by extracellular vesicles loaded with small interfering RNA

Abstract

AbstractRASis a well-known oncogene contributing to significant proportion of cancer incidences, yet it remains as an undruggable target to majority of therapeutic modalities. Here, we explored the potential of extracellular vesicles (EVs) for therapeutic targeting ofKRASmutation-driven tumorigenesis. EVs loaded with small interfering RNA (siRNA) againstKRASsuccessfully inhibited tumor xenograft growth when injected intratumorally in mice models. Intriguingly, when injected intravenously, EVs were still able to accumulate in tumors and deliverKRAStargeting siRNA payload in sufficient amount to show tumor growth inhibition. Therefore, EV-siRNA platform show great promises for therapeutic targeting ofKRASmutations and other undruggable targets.