Ionis is driven by an urgency to deliver medical breakthroughs for serious diseases that can change the course of human health. Our science is inspired by a deep understanding of the biology of disease and powered by our commitment to advancing next-generation technology.
We have a rich history of discovering and developing life-changing medicines that target RNA – a molecule that carries out the genetic instructions encoded in our DNA. Today, we are focused on harnessing advanced technology to create medicines that target and interact with both RNA and DNA to treat a variety of conditions – from common cardiometabolic disorders to intractable neurological conditions and rare diseases with few or no effective treatment options.
The advanced technology behind our medicines leverages oligonucleotides – small sequences of modified RNA – to precisely target and interact with RNA and DNA. We achieve this precision by tapping into the same biology used to store and process information in the genetic code – our genes. Our technology enables us to change the function or expression of a gene in a highly specific and directed manner, which, in turn, can help address the root cause of a disease.
For example, a gene called TTR contains instructions to make TTR protein, which can accumulate in tissues and cause disease. We have designed an RNA medicine that seeks out, binds to and destroys TTR RNA, which significantly reduces the levels of the disease-causing TTR protein.
Our technology can also increase or change the expression of a gene. For example, in spinal muscular atrophy (SMA) we have addressed the deficiency in a critical protein called SMN with a medicine that changes the “instructions” in RNA. This change enabled the production of the SMN protein, thereby addressing the root, genetic cause of the disease.
Advancing RNA and DNA Technologies to Power Future Medicines
We pioneered the field of RNA medicines and, specifically, antisense oligonucleotides (ASOs). ASOs are now a proven class of medicines that are used to treat a range of different diseases. Armed with our deep expertise and advanced technology, our focus is on discovering, developing and commercializing the RNA medicines of the future that hold the potential to change the lives of patients living with serious diseases.
Our approach is unique in that we employ multiple strategies to modulate gene expression:
Depending on the design of the ASO and the selected RNA target, we can modulate the function of the RNA in one of two ways:
- Degrade the RNA to inhibit its function, which can result in the reduction of a toxic RNA or a decrease in the production of an undesired protein
- Change the way the target RNA is processed to increase its function and any protein it encodes
Similar to ASOs, siRNAs can decrease the production of specific proteins involved in disease. Using our unique and proprietary chemistry we have engineered our siRNA therapies to have high potency, specificity and a long duration of effect.
With gene editing, we can add, remove or alter DNA sequences in a cell or organism. This allows us to increase, decrease or alter the function of a gene involved in a specific disease.
We translate these strategies into the RNA and DNA medicines of tomorrow by leveraging several chemical technologies, including some that are well-established in the field and others that represent more recent innovations.
We’re currently optimizing the following new and evolving technologies:
The MsPA backbone increases the biological stability and, therefore, duration of effect of RNA medicines – particularly ASOs. This innovation allows us to precisely tune the properties of an ASO for optimal performance in multiple tissues.
Bicycles are small peptide-based ligands that specifically bind proteins without adding much complexity to our medicines. We employ Bicycles that bind transferrin receptor 1 for use with oligonucleotides, which facilitates improved delivery of antisense medicines to muscle tissue, including cardiac muscle, as well as the potential to cross the blood brain barrier.
All of the potential first and/or best-in-class medicines in our clinical pipeline resulted from our innovative science and chemical technologies that allow us to target RNA and DNA. By unlocking the rapidly expanding potential of RNA and DNA medicines, we can transform their accuracy and efficacy and, ultimately, change the course of human health.