1. What are siRNA therapeutics, and how do they work?
siRNA therapeutics belong to a class of gene-silencing drugs that utilize small interfering RNA (siRNA) molecules. siRNAs are short, noncoding, double-stranded RNAs that leverage the RNA interference (RNAi) pathway to achieve highly specific gene silencing. They suppress gene expression by targeting and selectively degrading complementary messenger RNA (mRNA), through RNA-induced silencing complex (RISC). This approach offers a highly specific and targeted method for treating diseases, particularly those involving genetic mutations or protein overexpression.
2. Which regions are leading in siRNA therapeutics clinical trials, and what drives their growth?
Globally, siRNA clinical trials are led by Asia-Pacific region followed by North America and Europe. Rapid growth in the biotechnology sector coupled with investment in research, particularly in countries like China, Japan, and India fuels the expansion of siRNA therapeutics in Asia-Pacific. Also, the increasing prevalence of diseases and genetic disorders creates a demand for innovative treatments. In North America, particularly the USA, strong research infrastructure, investment and funding coupled with a favorable regulatory framework and expedited approval processes have encouraged the development of siRNA therapeutics. In Europe, collaborative research networks, government initiatives and funding programs support the advancement of siRNA therapeutics. Countries like Germany, France and the UK have strong pharmaceutical hub that drive clinical trial activities.
3. What are the latest advancements in siRNA therapeutics delivery methods?
Chemical modifications, conjugation strategies with ligands and aptamers, and nanoparticle-based delivery.
Lipid nanoparticle and GalNAc conjugation have revolutionized siRNA delivery, enabling liver targeted therapies. Lipophilic conjugates and protein conjugates expand delivery to CNS, eyes, lungs and muscles. Exosome-based and polymeric nanoparticle are emerging technologies for broader tissue targeting. Self-assembled RNA nanostructures for enhanced stability, CRISPR/siRNA hybrid approaches for precise gene control and light activated siRNA are other emerging technologies in siRNA delivery.
4. How do siRNA drugs integrate with combination therapies to improve outcomes?
siRNA therapeutics are increasingly being integrated into combination therapies to enhance efficacy, overcome drug resistance, and reduce side effects. By silencing specific disease related genes, siRNA therapeutics can complement traditional treatments like small molecules, monoclonal antibodies, immunotherapies, and chemotherapy. Their clinical applications as a combination therapy are being explored in oncology, neurological disorders, cardiovascular diseases, and infectious diseases.
5. What is the regulatory landscape for siRNA therapeutics and how does it vary globally?
siRNA therapeutics are regulated by US FDA through CDER and are treated similar to small molecules. In the EU, EMA evaluates siRNA therapeutics under the Committee for Medicinal Products for Human Use (CHMP), and Advanced therapy medicinal product (ATMP) regulations can apply to certain drugs which are reviewed under a mandatory centralized procedure. Japan regulates siRNA therapeutics through the Pharmaceuticals and Medical devices Agency (PMDA) and offers conditional and time limited approval. In China, siRNA therapeutics fall under biologic drug regulations by the National Medical Products Administration (NMPA). Australia uses a risk-based framework with pathways for accelerated approval.
The FDA and EMA allow foreign data with limited additional studies and offer fast-track designations, whereas China and Japan often require local data.