How RNAi Therapeutics Work
Our medicines use RNA interference (RNAi) to “silence” or turn off the production of specific genes that cause disease or that contribute to disease.
RNAi is a natural biological process that regulates gene expression by “interfering” with messenger RNA (mRNA), which carries DNA’s instructions for making new proteins. Our RNAi therapeutics mimic this process by delivering specially designed small interfering RNAs (siRNAs) that, as part of RISC (RNA-induced silencing complex), bind to target disease-causing mRNA and guide their destruction like a pair of molecular scissors.
By addressing genetically validated targets, our RNAi therapeutics work “upstream” of most other classes of medicines, such as small molecules and monoclonal antibodies.
How siRNAs Work
When the siRNA duplex is delivered into the cell, it is recognized by a protein complex known as the RNA-induced silencing complex (RISC), which already resides in the cell as a primary component of the natural RNAi pathway. Our siRNA duplex is recognized by and loaded into RISC, which removes one of the two strands (the “passenger” strand). This functional RISC now has only the complementary (or “guide”) strand that stays bound to the RISC, helping it find and pair with its matching (or “complementary”) mRNA before it is converted into a protein by a ribosome. Once the match is found, like a pair of molecular scissors, the siRNA together with RISC cleaves the “unwanted” target mRNA, causing it to be degraded. This process is catalytic, meaning that a single siRNA-loaded RISC can degrade many copies of the target mRNA. As a result, the production of the specific “unwanted” protein that corresponds to that mRNA is reduced or “silenced.”
Additionally, we believe that siRNAs can be developed to address infectious diseases by directly targeting viral RNA or their host factors for destruction such that the virus is unable make copies of itself or to get inside cells in the first place.
Key features of our RNAi therapeutics:
- Ability to target potentially any gene in the genome, including targets that are “undruggable” by small molecules and antibodies
- Highly potent and durable effect (dosing as infrequently as biannual or annual)
- Administration through multiple routes—intravenous (IV), subcutaneous, and inhalation delivery
- Demonstrated clinical benefit with a lower dose and dose frequency, and an encouraging overall safety profile compared to other approaches to gene silencing
- Modular, reproducible, and consistent performance across organs and diseases
*Licensed to Novartis
Our Pipeline
Learn about how we are leading the translation of RNAi (RNA interference) into a whole new class of innovative medicines.