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LASSO: A New Method for Highly Selective Biomolecule Isolation
The isolation of specific molecules from complex biological samples is crucial in healthcare and life sciences. Yet, many isolation methods are slow, expensive, and suffer from incomplete removal of contaminants. Now, reporting in Angewandte Chemie International Edition, a team led by Elisha Krieg describes LASSO (crossLink-Assisted Sequence-Selective isOlation), a new platform for sequence-selective biomolecule catch-and-release. LASSO uses DNA-based crosslinker libraries that self-assemble with a DNA-functionalized polymer, thereby forming highly permeable molecular networks. These networks capture targets and isolate them via a reversible phase-separation mechanism. Unlike conventional biomolecule pulldown assays, LASSO does not involve any solid-liquid interfaces, which prevents nonspecific adsorption and carryover of contaminants. The team demonstrates high performance across diverse target types, including DNA oligonucleotides, SARS-CoV-2 RNA, ribosomal RNA, and human thrombin protein. Relying on a fully synthetic set of components makes LASSO more stable, allows prolonged storage and cold-chain-free shipping, which is particularly beneficial in resource-limited settings.
Publication: Sarah K. Speed, Krishna Gupta, Yu-Hsuan Peng, and Elisha Krieg. Versatile and Selective Biomolecule Pulldown with Combinatorial DNA-Crosslinked Polymers. Angewandte Chemie International Edition. (2025).
05.01.2026