Therapeutic RNA aptamers in clinical trials.

RNA aptamers can fold into complex structures and bind with high affinity and selectivity to various macromolecules, viruses, and cells. They are isolated from a large pool of nucleic acids by a conceptually straightforward iterative selection process called SELEX. Aptamers have enormous potential as therapeutics due to their ability to bind to proteins and specifically inhibit their functions with minimal or no harmful side-effects. The first aptamer therapeutic was FDA approved in 2005 and a number of novel aptamer-based therapeutics are currently undergoing clinical trials for treating diseases such as macular degeneration, choroidal neovascularization, intravascular thrombus, acute coronary syndrome, von Willebrand factor related disorders, von Hippel-Lindau syndrome (VHL), angiomas, acute myeloid leukemia, renal cell carcinoma, non-small cell lung cancer, thrombotic thrombocytopenic purpura, and several others. In this review, we present aptamers in on-going, completed, and terminated clinical studies highlighting their mechanism of action as well as the inherent challenges of aptamer production and use.