RNA interference is a post transcriptional gene silencing process that is believed to have the potential to treat undruggable diseases. Unlike other drugs, which target a disease at the protein level, RNAi therapeutics target the mRNA that codes for proteins. Several companies, such as Alnylam Pharmaceuticals, Silence Therapeutics and Quark Pharmaceuticals have realized the potential of this market and are actively developing RNAi drugs to target various disease indications. The future of this market looks highly promising; however, careful analysis of the market indicates some challenges that need to be addressed. These factors are likely to determine the success and failure of the market and are anticipated to help in carving strategies for overcoming the weaknesses and threats to the market.
RNAi based therapeutics have demonstrated potential to treat previously undruggable targets, including rare genetic disorders, owing to its ability to perform sequence specific degradation of mRNA strands. Further, RNAi therapeutics are capable of treating different disease indications by targeting a common gene. For instance, Alnylam Pharmaceuticals has two RNAi therapeutics in its pipeline, Onpattro and Vutrisiran, that target the transthyretin (TTR) mutation. Although both the drug candidates, target the same gene, they are intended for different indications, namely hATTR amyloidosis and ATTR amyloidosis, respectively. It is worth mentioning that this market is characterized by the presence of a rich and growing pipeline, of which some drug candidates are likely to be approved in the near future.
One of the major challenges associated with the development of novel drug classes is the delivery of therapeutic agent to the target tissue. The challenge of delivering RNAi payload to target cells without metabolic clearance and immunogenicity is faced by players engaged in this domain. In order to elicit the therapeutic response properly, key considerations for a delivery technology include crossing RNAi payload through the biological barrier, selectively hitting the target, release of siRNA, high tolerance and high therapeutic index (ratio of therapeutic effect to toxicity). Often, size and charge of siRNA serves as an obstacle in the delivery to target cell or tissue. The current delivery vehicles used by developers include lipid-based nanoparticles, polymer-based nanoparticles, conjugated systems and delivery of naked siRNA.
Some disorders are caused due to multiple gene mutations along with other factors, such as lifestyle and environmental factors; these include cardiovascular disorders, genetic disorders and autoimmune disorders. Presently, not many effective treatments for such disorders are available in the market. However, RNAi based therapeutics have the potential to target multiple targets and thus, can effectively cure such diseases and provide relief to patients. It is worth noting that companies such as Alnylam and Arbutus Biopharma are developing RNAi based drugs that target disorders that are caused due to lifestyle habits and environmental factors; molecules of both the companies are currently in discovery stage.
Apart from RNAi, other technologies that use the gene silencing approach are also being developed. These technology platforms include CRISPR interference and antisense technology. RNAi technology regulates gene at mRNA level, while CRISPR interference controls expression at transcriptional level. This new technology could become a potential competitor of the RNAi as it provides additional advantages, such as inducing pluripotency in stem cells. Another competitor of the RNAi technique is antisense technology, which has significant number of approved therapies, such as Vitravene, Macugen and Exondys 51. This technology uses the antisense oligonucleotide to target the mRNA that binds with the single stranded mRNA. In addition, this technology has the scope to develop personalized oligonucleotides with therapeutic potential.