Abstract LB222: MRD Express: Rapid, scalable, and high-performance custom target enrichment for minimal residual disease monitoring

Abstract Detection of minimal residual disease (MRD) via liquid biopsy offers a high-sensitivity alternative to conventional radiographic imaging, enabling early detection of molecular relapse within clinically actionable decision windows. To achieve the necessary analytical sensitivity, MRD assays require tracking patient-specific circulating tumor DNA (ctDNA) variants using highly optimized, personalized NGS panels. However, the clinical utility of personalized MRD monitoring is often constrained by the complexity of panel design and lengthy manufacturing lead times. We present the Twist Bioscience MRD Express Panel, a scalable target enrichment workflow engineered to streamline the transition from variant characterization to repeat analysis across multiple samples. Leveraging a silicon-based DNA synthesis platform and proprietary design algorithms, we have automated the pipeline to achieve a rapid turnaround time of as little as one business day from synthesis to shipment. To ensure robust performance across challenging genomic regions, we implemented an innovative LNA (Locked Nucleic Acid) boosting strategy, enhancing coverage uniformity for probes with extreme GC content. Additionally, we assessed the feasibility of using LNAs to perform allele-specific targeting in the context of this capture system. This platform supports ultra-flexible panel sizes ranging from 1 to 10, 000 probes, allowing researchers to perform highly focused MRD tracking or broader exploratory research strategies. Fully compatible with existing Twist NGS library preparation and hybrid capture workflows, MRD Express provides a high-throughput, "N-of-1" solution that maintains the performance of centralized manufacturing with the speed required for precision oncology research. Citation Format: Shawn Gorda, Elian Lee, Michael Bocek, Sean Tighe, Siyuan Chen. MRD Express: Rapid, scalable, and high-performance custom target enrichment for minimal residual disease monitoring abstract. In: Proceedings of the American Association for Cancer Research Annual Meeting 2026; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts) ; 2026 Apr 17-22; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2026;86 (8Suppl): Abstract nr LB222.