Our GalXC™ technology platform
Our proprietary GalXC technology leverages a naturally occurring biologic process, ribonucleic acid interference, RNAi, to create therapies that silence disease-causing genes. This platform enables Dicerna to create molecules that can effectively interfere with the RNAi processes that lead to defective or misregulated proteins that cause disease.
How RNAi therapies work and their advantages
The DNA within each of us is essentially an “instruction manual” for building proteins that greatly affect our health. Our messenger RNAs (mRNAs) carry these instructions from the DNA to sites in cells where proteins are made. During this biologic process, small interfering RNA (siRNA) molecules induce the destruction of the mRNAs of targeted genes.
Because scientists can easily create synthetic siRNAs that match almost any mRNA, this RNAi-based approach to drug development can silence virtually any gene and has distinct advantages over more traditional therapeutic approaches, including:
- RNAi has an impact earlier in the disease-causing process. RNAi can be used to target any gene because it targets the mRNA that encodes the disease-driving protein. While some conventional therapies block the activity of proteins responsible for disease, RNAi therapies prevent them from being created.
- RNAi is highly specific for the targeted gene because it uses a gene sequence match with the targeted gene and relies on naturally occurring cellular enzymes to mediate gene silencing. RNAi therapies are thought to be a safer option than permanently editing DNA, which could have unknown, unwanted and irreversible consequences. Conversely, RNAi therapies are reversible. RNAi therapies have the potential for fewer side effects compared to small molecules and antibodies.
- RNAi therapies also have the potential to reduce the treatment burden for patients. Their long duration of effect means they can be administered through infrequent injections under the skin.
GalXC: Liver diseases are just the start
GalXC molecules are Dicerna’s proprietary form of siRNAs. Our powerful platform enables us to develop highly selective and specific RNAi compounds that have a unique configuration known as a tetraloop. This configuration interfaces effectively with the RNAi process and allows us to easily modify a compound’s chemical structure to maximize stability and potency.
Dicerna’s Tetraloop Configuration
Our scientists are exploring the use of GalXC technology beyond the liver in other organ systems, including neural tissues, to address a broad range of other diseases.
Data from clinical and preclinical studies suggest that GalXC may offer several benefits, including:
- Potentially stronger potency than comparable RNAi therapies
- Highly specific binding to disease-causing targets
- Long duration of action
- An infrequent, subcutaneous dosing regimen, which can minimize treatment burden
- A high therapeutic index, which indicates broad applicability
Leaders in the RNAi revolution
Novo Nordisk and Dicerna announce a global licensing and research collaboration focused on cardiometabolic diseases.
Roche and Dicerna announce a global licensing and research collaboration focused on chronic hepatitis B virus infection.
Dicerna submits a clinical trial authorization (CTA) application to conduct a first-in-human Phase 1/2 study of DCR-A1AT for the treatment of alpha-1 antitrypsin (A1AT) deficiency-associated liver disease.
Dicerna initiates first dosing in Phase 1 clinical trial of DCR-HBVS for the treatment of hepatitis B virus infection.
Eli Lilly and Dicerna announce a global licensing and research collaboration focused on creating new medicines in cardiometabolic disease, neurodegeneration and pain.
Alexion Pharmaceuticals and Dicerna announce a collaboration to create RNAi therapies for complement-mediated diseases.
FDA approves first RNAi therapy.
Dicerna initiates PHYOX™ Phase 1 clinical trial in patients with primary hyperoxaluria type 1 (PH1) and type 2 (PH2)
Boehringer Ingelheim and Dicerna announce research collaboration and license agreement to develop novel GalXC RNAi therapies for chronic liver diseases, beginning with nonalcoholic steatohepatitis (NASH).
Dicerna introduces GalXC, our proprietary, next-generation, RNAi technology platform.
Dicerna receives a U.S. patent for its Dicer Substrate™ technology, a precursor to our current GalXC platform.
The City of Hope (COH) grants Dicerna exclusive worldwide license for Dicer substrate short interfering RNA (DsiRNA), the inspiration for Dicerna’s GalXC RNAi platform.
Fire and Mello receive the Nobel Prize for their discovery of RNAi.
Andrew Fire and Craig Mello publish their discovery of RNAi in Nature.