Emergence of Covid-19 and High Prevalence of Neurological Diseases to Boost Demand for Antisense Oligonucleotides

 

Antisense oligonucleotides are short, synthetic, single-stranded oligodeoxynucleotides that hybridize to a target RNA in a sequence-specific manner. These synthetic DNA oligomers find application in antisense therapy for the treatment of cancer, virus infections, and inflammatory diseases. A major benefit of antisense oligonucleotides-mediated therapies is their ability to target the source of the pathogenesis, which increases the outcome of the treatment. Such benefits have prompted approval of these therapies in the U.S. for the treatment of diseases such as Duchenne muscular dystrophy and spinal muscular atrophy. Other approved conditions include, Batten disease, cytomegalovirus retinitis, familial chylomicronaemia syndrome, familial hypercholesterolemia, and hereditary transthyretin-mediated amyloidosis.

Recently, emergence of Covid-19 has led to R&D in designing antisense oligonucleotide gapmers to cleave the RNA and disrupt virus replication. This can be attributed to highly conservative nature of a part of the SARS-CoV-2 viral RNA. The novel approach can allow use of s2m or stem-loop 2 motif (s2m), a highly conserved sequence in the Sarbecovirus genus, as a potential target for developing antivirals.

Antisense oligonucleotides can be used to inhibit gene expression, modulate splicing of a precursor messenger RNA, or inactivate microRNAs. It has also been observed that targeted cell- and tissue- specific delivery of these oligonucleotides help in treatment of various diseases with high unmet medical need. In this regard, in January 2020, Aro Biotherapeutics, a company focused on R&D of a new generation of protein biologics, collaborated with Ionis Pharmaceuticals, Inc., a developer of RNA-targeted therapeutic solutions, to develop targeted cell- and tissue- specific delivery of antisense oligonucleotides.

Antisense oligonucleotides have shown potential in the treatment of Prion disease, a type of proteopathy, or disease of structurally abnormal proteins. This neurodegenerative disease can adversely impact the nervous system. Use of antisense oligonucleotides has been found to prolong the lives of mice in lab experiments.