When the drug fomivirsen was approved by the FDA in 1998 for the treatment of cytomegalovirus retinitis in patients with HIV/AIDs, it was hailed as a milestone in drug discovery because it was the first antisense oligonucleotide (ASO)—a class of drugs that works by targeting RNA to alter gene expression and control aberrant proteins in ways that traditional drugs can’t. An additional nine ASOs have since been approved by the FDA.To look into the future of the ASO class, it’s helpful to first understand its history. The method was first described in the late 1970s by two Harvard scientists who used unmodified DNA ASOs to inhibit viral RNA translation in the Rous sarcoma virus. The following decade brought rapid innovations in antisense methods, including improvements in the stability and binding affinity of ASOs, which in turn improved their potency.

More recently, scientists working in the ASO field discovered certain advantages when targeting RNA species in the cell nucleus. This led to the discovery of novel targets, including long-noncoding-RNAs, which are responsible for regulating gene transcription and post-translational modifications. During the 2010s, several ASO-class therapeutics were approved by the FDA, including nusinersen for spinal muscular atrophy, and eteplirsen and casimersen for Duchenne muscular dystrophy.Another factor bolstering the development of ASO therapeutics is the push that’s underway to support the development of new therapies to treat rare diseases. Earlier this year, the FDA’s Center for Biologics Evaluation and Research said it was preparing to pilot test a program aimed at rare diseases that’s modeled after Operation Warp Speed, the government’s effort to accelerate the development of Covid-19 vaccines. The hope is to reduce the time and expense of developing genomic therapies to treat rare diseases. Likewise, the Nucleic Acid Therapy

The N1C is a collaborative formed from several foundations and institutions with the goal of increasing the pace of development of treatments for rare genetic disorders via a variety of new technologies, including antisense, RNA interference, and CRISPR genome editing.

Source: https://medcitynews.com/2023/10/fostering-the-next-generation-of-antisense-oligonucleotide-therapies/