Why promoter design is no longer just an expression checkbox, it’s the key to therapeutic endurance:
Advanced therapies Why promoter design is no longer just an expression checkbox, it’s the key…
27 July 2026
This week, the ALS community reached a significant milestone. Our partner, VectorY Therapeutics, announced the first patient has been dosed in their Phase 1/2 PIONEER-ALS clinical trial for VTx-002.
VTx-002 represents a potential paradigm shift in treating Amyotrophic Lateral Sclerosis (ALS) by targeting TDP-43 — the protein pathology found in nearly 97% of all ALS cases. At Annogen, we are proud to share that this first-in-class vectorized antibody is powered by a bespoke, human genome-based promoter identified by Annogen, underlining the value we bring to gene therapy development.
While we celebrate the clinical progress, this moment also signals a deeper shift in how the industry approaches gene therapy design.
The development of regulatory elements for the expression of gene therapies can go through various strategies.
On one side, “conservatives” remain tethered to traditional viral promoters including SV40, CMV and CBh. While familiar, these are blunt instruments; they often lack the cell-type precision and sophisticated safety profiles, frequently face both silencing and host immune responses.
On the other spectrum, a new wave of the industry has rushed toward AI-predicted promoters. Using computational predictions for the development of regulatory elements is powerful and will remain fundamental to the future of gene expression engineering, but this is on the assumption that it has high-quality, sensitive data to train on. AI is only as powerful as the data it consumes, and in the world of genomics, that data is frequently incomplete, unsensitive, or lacks the functional context of a patient’s body. Hence, when these computational predictions are biological reality, we know they often struggle to perform.
At Annogen, we believe the way to build a therapy that stands up to clinical rigor is to start from experimental data and thorough validations. We therefore don’t provide promoters, based on reasoning; we functionally screen the full genome in high redundancy.
Using our proprietary SuRE™ platform, we digest the human genome into 6 million fragments and test each of these individually, in parallel, a hundred times each. We then take the top performing elements – promoters and enhancers – and make >100,000 combinations and again test these, from which we pick and thoroughly validate the top candidates. The resulting promoter is ensured to be tailored to a therapy’s needs for specificity, strength and persistence, which outleagues any viral promoter or AI-based prediction.
