High-throughput in vivo discovery of microRNA leukemia therapeutics

Despite dramatic improvements in survival using current therapies, relapse is the most frequent cause of cancer-related death among children with B-cell precursor acute lymphoblastic leukemia (BCP-ALL). This is due, in part, to disease progression, drug resistance, and a lack of targeted drug delivery systems. MicroRNAs play a critical role in the initiation, progression, and drug resistance of ALL, and microRNA-based therapies can potentially overcome ALL drug resistance by reducing the expression of oncogenes. However, microRNA therapies have been hampered by a lack of efficacious nucleic acid delivery systems. As a novel paradigm for ALL therapy, we propose a nanotechnology platform that delivers microRNA therapeutics, reduces systemic toxicity, and overcomes ALL resistance to clinical therapeutics. The proposed studies have the potential to improve public health and patient outcomes through new therapeutics that alleviate suffering, replace less efficacious options, and reduce the overall treatment cost of ALL and potentially other hematologic malignancies.