An ounce of prevention is worth a pound of purification
Anonymous
The dsRNA impurities that arise during current RNA manufacturing approaches are generated from the target RNA itself, with >50 additional bases added to its end. The resulting double stranded (dsRNA) triggers our innate immune response, thinking that the cells is being attacked (it’s not!). In addition to triggering inflammation (acceptable at low levels for vaccines), this can lead to a shut down of translation, requiring higher levels of therapeutic.
Purifying 4,000 base target RNA from 4,050 base dsRNA (for example) is very hard. It is costly. It reduces yield. And it is essentially impossible to knock dsRNA down to zero through purification post-synthesis.
dsRNA is generated during the initial synthesis, by the RNA polymerase itself. We understand how/why this happens. And we understand how to prevent it at the outset. Our goal is zero detectable levels of dsRNA, before purification. This can lead to lower dosing, but more importantly, it will allow progression of therapies currently stuck in the pipeline. Our goal is clinical trials that allow a wide variety of RNA therapeutics to reach their full potential!
As an extra benefit, the streamlined manufacturing process will be substantially less expensive and more amenable to GMP grade production of therapeutics.