RNA aptamers can be designed to act as antagonists, agonists, or so-called ”RNA decoy aptamers." In the case of antagonists, the RNA aptamer is used either to prevent binding of a certain protein to its cell membrane receptor or to prevent the protein from performing its activity by binding to the proteins target. Currently, the only RNA aptamer-based therapies that have advanced to clinical trials act as antagonists. When RNA aptamers are designed to act as agonists, they promote immune cell activation as a co-stimulatory molecule, thus aiding in the mobilization of the bodys own defense system. For RNA decoy aptamers, the synthetic RNA aptamer resembles a native RNA molecule. As such, proteins(s) which bind to the native RNA target instead bind to the RNA aptamer, possibly interfering with the biomolecular pathway of a particular disease. In addition to their utility as direct therapeutic agents, RNA aptamers are also being considered for other therapeutic roles. For instance, by conjugating the RNA aptamer to a drug compound, the RNA aptamer can act as a targeted delivery system for that drug. Such RNA aptamers are known as ApDCs. Additionally, through conjugation to radioisotope or a fluorescent dye molecule, RNA aptamers may be useful in diagnostic imaging.
Because of the SELEX process utilized to select RNA aptamers, RNA aptamers can be generated for many potential targets. By directly introducing the RNA aptamers to the target during SELEX, a very selective, high-affinity, homogeneous pool of RNA aptamers can be produced. As such, RNA aptamers can be made to target small peptides and proteins, as well as cell fragments, whole cells, and even specific tissues. Examples of RNA aptamer molecular targets and potential targets include vascular endothelial growth factor, osteoblasts, and C-X-C Chemokine Ligand 12 (CXCL2).
An example of an RNA aptamer therapy includes Pegaptanib (aka Macugen ® ), the only FDA-approved RNA aptamer treatment. Originally approved in 2004 to treat age-related macular degeneration, Pegaptanib is a 28 nucleotide RNA aptamer that acts as a VEGF antagonist. However, it is not as effective as antibody-based treatments such as bevacizumab and ranibizumab. Another example of an RNA aptamer therapeutic is NOX-A12, a 45 nucleotide RNA aptamer that is in clinical trials for chronic lymphocytic leukemia, pancreatic cancer, as well as other cancers. NOX-A12 acts as antagonist for CXCL12/SDF-1, a chemokine involved in tumor growth.