text: Since at least the mid-2000s, there has been intensifying interest in developing short interfering RNAs for biomedical and therapeutic applications. Bolstering this interest is a growing number of experiments which have successfully demonstrated the clinical potential and safety of small RNAs for combatting diseases ranging from viral infections to cancer as well as neurodegenerative disorders. In 2004, the first Investigational New Drug applications for siRNA were filed in the United States with the Food and Drug Administration; it was intended as a therapy for age-related macular degeneration. RNA silencing in vitro and in vivo has been accomplished by creating triggers (nucleic acids that induce RNAi) either via expression in viruses or synthesis of oligonucleotides. Optimistically many studies indicate that small RNA-based therapies may offer novel and potent weapons against pathogens and diseases where small molecule/pharmacologic and vaccine/biologic treatments have failed or proved less effective in the past. However, it is also warned that the design and delivery of small RNA effector molecules should be carefully considered in order to ensure safety and efficacy.
  The role of RNA silencing in therapeutics, clinical medicine, and diagnostics is a fast developing area and it is expected that in the next few years some of the compounds using this technology will reach market approval. A report has been summarized below to highlight the many clinical domains in which RNA silencing is playing an increasingly important role, chief among them are ocular and retinal disorders, cancer, kidney disorders, LDL lowering, and antiviral. The following table displays a listing of RNAi based therapy currently in various phases of clinical trials. The status of these trials can be monitored on the ClinicalTrials.gov website, a service of the National Institutes of Health (NIH). Of note are treatments in development for ocular and retinal disorders, that were among the first compounds to reach clinical development.  AGN211745 (sirna027) (Allergan) and bevasiranib (Cand5) (Opko) underwent clinical development for the treatment of age-related macular degeneration,  but trials were terminated before the compounds reached the market. Other compounds in development for ocular conditions include SYL040012 (Sylentis) and QPI-007 (Quark). SYL040012 (bamosinan) is a drug candidate under clinical development for glaucoma, a progressive optic neurdegeneration frequently associated to increased intraocular pressure; QPI-007 is a candidate for the treatment of angle-closure glaucoma and Non-arteritic anterior ischaemic optic neuropathy; both compounds are currently undergoing phase II clinical trials. Several compounds are also under development for conditions such as cancer and rare diseases.