White Paper:

Although meaningful progress toward the development of oligonucleotide therapeutics began in the 1970s, nearly a half century later, only three oligonucleotide drugs have been approved by the FDA. However, the field is gaining momentum and the clinical benefits of the more than 135 oligonucleotide therapeutics currently in various stages of clinical trials are extremely promising.

THE PROMISE & OPPORTUNITIES
What is so attractive about oligonucleotide therapeutics? Although this class of therapeutics is quite diverse, the excitement and dedication to this work is rooted in the following factors:

• Oligonucleotides offer promising treatment for a wide range of medical conditions.

• They allow for the development of therapeutics that affect protein targets that cannot be effectively treated by small-molecule or protein therapeutics.

• Interfering with RNA function at the cellular level, specific malfunctioning genes can be targeted, manipulated, silenced and/or modulated.

• Immune system modification is possible, offering the possibility of treatment for a multitude of autoimmune disorders that are in many cases extremely challenging to treat with currently available drugs.

• Oligonucleotides are synthesized pieces of chemically modified RNA or DNA. Scaling up for commercial-scale GMP production is more feasible than it is for many cell therapies or other biologic therapies.

• Side effects for many oligonucleotides are more controllable and minimal than the side effects experienced with other classes of drugs.

• As reported by Ryszard Kole in 1993, oligonucleotides can be used to modulate pre-mRNA splicing. Much work has been done to develop therapies targeting Duchenne muscular dystrophy, including progress treating the splicing mutation that causes Duchenne muscular dystrophy. These learnings hold much promise for a number of other conditions as well.

• In concept, when compared to small-molecular drugs as well as to large-molecule biopharmaceuticals, oligonucleotide pharmaceuticals are much more straightforward to both design and develop.