Technology for Nucleic Acid Delivery in the Treatment of Hematological Malignancies

Abstract

Blood (hematological) cancers display a wide spectrum of etiologies that can be attributed to specific molecular and chromosomal changes. While the uncontrolled proliferation of blood cells could be controlled to some degree by conventional anti-neoplastic agents, advanced therapies are needed to enhance the chances of survival. Nucleic acid therapeutics offer a great promise in combating blood cancers; they could be tailored to address the root cause of the diseases and can be deployed on their own or in combination with clinical drugs to achieve superior outcomes. In this review, we summarize the technology of delivering nucleic acids for the treatment of blood cancers. We start with the review of common types of hematological malignancies, highlighting the molecular pathology behind the malignancies. We then articulate the spectrum of nucleic acids promising for therapy as well as their critical features for delivery and securing efficacious outcomes. Since it is well recognized that the critical challenge is deploying nucleic acids safely in a clinical setting, we focus on the more-predictable, leading synthetic carriers promising for delivery of nucleic acids in clinics. We emphasize synthetic carriers that form supramolecular complexes with nucleic acids, resulting in nanoparticulate formulations, as well as approaches to derivatize the nucleic acids to make them suitable for cellular uptake and targeted delivery. We then summarize highly promising attempts to tackle blood cancers using new approaches, emphasizing microRNA-mediated gene regulation and the CRISPR-based gene editing approaches. These new approaches are interrogated especially from the perspective of delivery technology, with the purpose of designing improved delivery systems. We conclude with the authors' perspective on the future of nucleic acid therapeutics for the treatment of blood cancers, providing authors' perspectives for significant advances in the field.