2025-10-09 ワシントン大学 (UW)
Therapies that are sensitive to multiple biomarkers could allow medicines to reach only the areas of the body where they are needed. The diagram above shows three theoretical biomarkers that are present in specific, sometimes overlapping areas of the body. A therapy designed to find the unique area of overlap between the three will act on only that area.DeForest et al./Nature Chemical Biology
<関連情報>
- https://www.washington.edu/news/2025/10/09/programmable-proteins-targeted-drug-delivery-synthetic-biology/
- https://www.nature.com/articles/s41589-025-02037-5
自律的にコンパイルされた分子トポロジーによるブール論理ゲート型タンパク質プレゼンテーション Boolean logic-gated protein presentation through autonomously compiled molecular topology
Ryan Gharios,Murial L. Ross,Annabella Li,Shivani P. Kottantharayil,Jack Hoye & Cole A. DeForest
Nature Chemical Biology Published:09 October 2025
DOI:https://doi.org/10.1038/s41589-025-02037-5
Abstract
Stimulus-responsive materials have enabled advanced applications in biosensing, tissue engineering and therapeutic delivery. Although controlled molecular topology has been demonstrated as an effective route toward creating materials that respond to prespecified input combinations, prior efforts suffer from a reliance on complicated and low-yielding multistep organic syntheses that dramatically limit their utility. Harnessing the power of recombinant expression, we integrate emerging chemical biology tools to create topologically specified protein cargos that can be site-specifically tethered to and conditionally released from biomaterials following user-programmable Boolean logic. Critically, construct topology is autonomously compiled during expression through spontaneous intramolecular ligations, enabling direct and scalable synthesis of advanced operators. Using this framework, we specify protein release from biomaterials following all 17 possible YES/OR/AND logic outputs from input combinations of three orthogonal protease actuators, multiplexed delivery of three distinct biomacromolecules from hydrogels, five-input-based conditional cargo liberation and logically defined protein localization on or within living mammalian cells.
