Hi @sorte,
Great find and thanks for bringing this study up. These therapies are depending on a technology similar to CRISPR/Cas (originally found in bacteria), but these were first discovered in algae in the 70s. My understanding is that Precision are able to make different versions of the ARCUS enzyme and “evolve” it to target a particular sequence with increasingly high specificity. They have developed one to HBV and have used it to deliver into cells and animal models, with HBsAg-lowering effects to enough of a degree that they have begun clinical trials. This press release describes the first of these.
These appear to be trials evaluating dosage and reporting findings so far for the lowest of 3 doses in 3 patients. It’s hard to say much about this without the data, but it sounds like the therapy itself is not harming the patients at this dose and that they see some reduction in viral targets (unknown how many patients and how much).
There is a worry about what happens to the HBV DNA after it is cut up with enzymes such as this. The strand of DNA is theoretically able to insert into the host genome (it’s unclear how often this happens) or reform into another cccDNA (which may contain mutations or still be able to express some viral proteins, even if it can’t produce more virus). There are a lot of unknowns at the moment for this, which hopefully will be clarified during the year as they present the results.
Hope this gives some context.
Cheers,
Thomas