Technology
SoAP selects for what a peptide does — not merely for how tightly it binds.
A functional phage display. The sole external requirement in a screening process is a defined target, usually an illness-related protein.
The premise
An idea from 2000 that turned out to be right.
Within the phage display family, most members return binders: sequences that stick to a target. AEBi's platform was designed around a harder question: whether selection, from the outset, can favour molecules that change what the target does.
SoAP does exactly that, and it does it against targets that have historically been awkward for this class of technology. That capability allows AEBi to operate on both sides of the business: as a screening partner for other companies, and as a drug discovery company in its own right.
Because selection is functional, the leads that come out already have a plausible mechanism — which is expected to reduce the attrition that normally eats the early phases of discovery. Selection biases the output toward function; it does not certify it, so whether a given peptide acts on the target is settled experimentally.
Throughout the process, ELISA is run on the peptides as displayed on the phage surface, never on free synthetic peptides. Synthesis, if required, follows the selection and is a separate step.
The problem SoAP addresses
A functional screen is only as good as the artefacts it removes.
Conventional phage display produces binders by construction, and several of them are artefacts of the method rather than properties of the target. SoAP's selection design is built around the four failure modes below.
- 01Target deformationAttaching a protein to a solid support can distort its native conformation, so selection runs against a partly artificial shape rather than the real target.
- 02Non-specific bindingSurfaces attract phage and peptides independently of the target. Such clones survive selection without recognising anything relevant.
- 03Deletion mutantsTruncated or misfolded library members can read as hits while carrying no usable sequence for downstream work.
- 04Infection biasClones that infect or grow more efficiently dominate the output regardless of how well — or whether — they act on the target.
Differentiating properties
Three properties that change the outcome.
Every round selects for function
In the SoAP platform each selection round carries both affinity and efficacy properties. The output is not the tightest binders but molecules selected for a defined effect on the target. This is selective pressure toward functionality, not a guarantee: SoAP does not undertake that every peptide delivered will prove functional, and functional activity is confirmed experimentally for each candidate.
Capacity from a vast library
Leads are isolated from combinatorial peptide libraries large enough to reach targets that conventional campaigns struggle with — including difficult and previously unexplored proteins.
Controllable selection conditions
Selection conditions can be altered to isolate leads with particular functional characteristics: agonists, antagonists, inhibitors. Unusually high signal-to-noise is what makes that possible.
Advantages
Compared with existing technologies.
- Success rate
- Rapid isolation and identification of lead compounds — and a platform built to hit and activate or deactivate protein-based targets.
- Capacity
- Isolation of leads from vast libraries, which dramatically expands the range of targets, including the most challenging ones.
- Optimization
- Selection can be tuned toward a desired functional profile rather than a generic binding event.
History
From an idea to a working platform.
2000
Dr. Ilan Morad proposes a functional phage display, and applies to the ITEK incubator at the Weizmann Science Park.
2006
AEBi demonstrates experimentally that the platform — SoAP — works.
Today
The same platform screens partners' targets and drives AEBi's own MuTaTo programme. The IP is protected.
Collaboration
Evaluation of a specific target.
A target description is sufficient to begin: AEBi will assess, objectively, whether SoAP is technically appropriate for it.
Discuss a target