RheumaGen innovation starts with our breakthrough HLA gene-editing technology.
Human leukocyte antigen (HLA) markers are genetic sequences that the immune system uses to identify which cells belong in your body and which do not.
In people with autoimmune diseases, the HLA molecules erroneously identify and present healthy cells to be attacked by the body’s defenses.
Each person has a specific HLA type, recognized by the body as its own, that is embedded in its cells. This is why, for example, organ donors and recipients must match HLA type (among other requirements) for a successful organ transplant. If the HLA type doesn’t match, the recipient’s immune system will reject the organ.
For more than forty years, immunology canon has maintained that you can’t introduce a new or altered HLA molecule into the body. Just as the immune system would reject an organ with a non-matching HLA type, it’s expected that the immune system would reject cells with an altered HLA molecule. As a result, most therapies targeting autoimmune diseases attempt to address disease processes downstream from the initial HLA trigger. These therapies can have limited success and cause major side-effects, such as suppressing the entire immune system (so it’s harder to fight off the cells that really don’t belong, like viruses and infections).
Here’s where RheumaGen’s technology changes everything.
Using bioinformatics, our expertise in HLA immunology (honed by 25 years of organ transplant and stem cell research), and new advances in gene editing, we’ve been able to engineer tiny changes to sequences deep within the HLA gene that are invisible to the immune system, but can still stop autoimmune disease.
Our lead preclinical therapy for refractory rheumatoid arthritis (RA), RG0401 edits the HLA gene so that it no longer triggers the patient’s immune system to attack the body’s healthy collagen cells. Instead, RG0401 edits the gene so that it creates HLA molecules like those of a person who is resistant to RA. This precision editing, however, leaves the rest of the immune system intact and unchanged, so it’s able to fight off viruses and other diseases the way it should.
Without the HLA gene triggering the T-cells to attack its own healthy cells, the T-cells go quiet and the disease process stops – without compromising the body’s overall immune response.
RG0401 is being designed as a one-time, outpatient procedure for patients with refractory rheumatoid arthritis:
The ability to modify the HLA molecule without rejection makes possible our revolutionary therapeutic approach to autoimmune disease.
We are using this technology to develop treatments for rheumatoid arthritis, ankylosing spondylitis, multiple sclerosis, type 1 diabetes, and celiac disease.
