Project Background
A biotechnology client was pursuing a transcription factor program in oncology but had not identified a credible small-molecule warhead for the protein. The team wanted to explore whether a double-stranded oligonucleotide decoy could be converted into a degrader format capable of inducing target loss in tumor cells, while also generating stronger mechanistic evidence than standard binding assays could provide.
Our Support
We began by analyzing the target's DNA-recognition motif, nuclear localization behavior, and degradation suitability, then designed three decoy sequence families and two E3 recruitment formats in parallel. To improve the probability of success, we evaluated multiple attachment positions and linker architectures rather than relying on a single conjugation hypothesis. In the first design round, 18 conjugates were synthesized and screened in reporter and degradation-oriented assays. Several constructs showed target engagement but only modest protein reduction, so the second round focused on phosphorothioate optimization, terminal stabilization, and shorter linker variants. This produced 4 improved conjugates, of which 2 delivered reproducible target degradation, clear concentration dependence, and stronger downstream transcriptional suppression than the client's original decoy control. The project gave the client a practical starting series and a validated optimization direction.
Client Testimonial
BOC Sciences helped us translate a conceptually attractive but technically uncertain decoy idea into a structured degrader program. Their iterative design logic and mechanism-focused testing made the results much easier to interpret and act on.
Project Background
An innovative discovery company was interested in degrading an RNA-binding protein (RBP) linked to abnormal protein aggregation in neurodegeneration. The scientific challenge was not only target binding, but also how to balance RNA-motif recognition, oligonucleotide stability, and intracellular delivery in a format suitable for meaningful cellular proof of concept.
Our Support
We first mapped known RNA-recognition preferences of the target and selected two high-confidence motif classes for degrader design. The team then generated 24 candidate conjugates spanning different sequence lengths, terminal chemistries, and CRBN- or VHL-oriented recruitment options. Early screening identified one motif family with consistently better target engagement, but activity was limited by cellular uptake and conjugate stability. To address this, we refined the backbone chemistry, introduced end-protection modifications, and compared delivery-assisted versus non-assisted testing conditions. In the optimized set, 3 candidates showed marked improvement in intracellular exposure and target reduction, with the top construct combining the best degradation signal, acceptable stability, and a cleaner functional profile in the client's disease-relevant cell model. The client used the resulting data package to prioritize the next discovery phase.
Client Testimonial
The BOC Sciences team brought a strong understanding of both degrader design and oligonucleotide behavior. Their work helped us identify which variables really mattered and prevented us from spending time on low-value design directions.
Expands Access to Hard-to-Drug Targets
