By delivering rapid, native‑context aptamer identification with kinetic insight, SPARK‑seq can shorten development cycles for high‑affinity molecular probes, boosting targeted drug delivery and diagnostic assay design.
Aptamer discovery has long been hampered by low‑throughput screening and the difficulty of preserving native protein conformations. Traditional selection methods, such as SELEX, require multiple rounds of enrichment and often yield candidates that perform poorly in physiological settings. SPARK‑seq addresses these bottlenecks by embedding CRISPR‑mediated gene knockouts within a single‑cell multi‑omics workflow, allowing researchers to simultaneously capture gene expression, protein binding and genetic perturbations. This multimodal data stream transforms millions of binding events into high‑dimensional sequencing reads, enabling systematic exploration of the aptamer‑target landscape at unprecedented scale.
The platform’s analytical engine, SPARTA, leverages deep‑learning models trained on the rich single‑cell dataset to predict binding affinity and kinetic profiles. In the initial study, more than 8,000 cells were profiled, revealing over 5,500 unique aptamer sequences targeting proteins such as PTK7, CDCP1 and members of the PTPR family. Notably, SPARK‑seq preferentially enriches aptamers with slow dissociation rates, a characteristic essential for reliable diagnostics and therapeutic efficacy. The 97 % prediction accuracy reported demonstrates the power of integrating computational inference with experimental throughput, opening the door to rapid iteration of aptamer variants with optimized performance.
For the biotech industry, SPARK‑seq represents a paradigm shift in molecular probe development. Faster identification of high‑specificity aptamers reduces R&D timelines and costs, while kinetic profiling ensures candidates meet clinical stability requirements. The technology is poised to accelerate precision‑medicine initiatives, from targeted drug delivery systems to point‑of‑care diagnostic platforms. As the platform matures, broader adoption could catalyze an “aptomics” era, where large‑scale, data‑driven aptamer libraries become a standard resource for therapeutic and diagnostic innovation.
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