Targeted RNA therapeutics for treatment of cancer and immunomodulation

RNA therapeutics have unique potential to target previously undruggable regulators of oncogenesis and tumor immunosuppression, making them an attractive tool for the treatment of cancer. However, the clinical application of oligonucleotide strategies has been limited by common challenges with the delivery of oligonucleotides to selected target cells and organs and by the unwanted immunostimulatory effects. Recent advances brought several strategies overcoming such limitations using conjugation of oligonucleotides with various types of targeting moieties such as monoclonal antibodies, DNA and RNA aptamers, TLR ligands, or small molecules. In addition, immune system has been recognized as a valuable target for oligonucleotide therapeutics that can address the complexity of immune cell network. In this chapter, we review these emerging oligonucleotide delivery strategies specifically for applications in cancer immunotherapy and immunomodulation.