組織内の数千種類のタンパク質を「衛星地図」のように可視化(Creating ‘Satellite Maps’ of Thousands of Proteins Across Tissue Could Transform Drug Therapies)

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2026-10-20 バッファロー大学(UB)

米国ニューヨーク州立大学バッファロー校のJun Qu教授らは、組織全体におけるタンパク質の分布を高精度で可視化する「六角形マイクロ足場支援空間プロテオミクス(hex-MASP)」技術を開発した。3Dプリンターで作製した六角形の微小区画を持つ足場で組織を細分化し、各試料の位置情報を維持したまま、超高感度質量分析によってタンパク質を定量する。これにより、組織切片全体における数千種類のタンパク質の分布を個別の地図として再構築できる。マウス脳にモノクローナル抗体を投与した実験では、薬剤の分布と6,000種類を超える脳内タンパク質の分布を同時にマッピングした。この手法により、薬剤が標的部位に到達しているか、組織内のどこで作用し、どのような生物学的変化を引き起こすかを詳細に調べられる。アルツハイマー病などの難治性疾患について、新たな創薬標的の発見、薬効や副作用の予測、臨床試験前の候補薬評価の改善につながることが期待される。

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Hex -MASPを用いた組織全体の空間プロテオームマッピングおよびモノクローナル抗体の脳内分布解析 Hex-MASP for mapping the whole-tissue spatial proteome and the intrabrain distribution of monoclonal antibodies

Shihan Huo, Min Ma, Shuo Qian, +7 , and Jun Qu
Proceedings of the national academy of Sciences  Published:September 3, 2026
DOI:https://doi.org/10.1073/pnas.2532946123

組織内の数千種類のタンパク質を「衛星地図」のように可視化(Creating ‘Satellite Maps’ of Thousands of Proteins Across Tissue Could Transform Drug Therapies)

Abstract

Whole-tissue level spatial proteomics provides critical insights into region-specific biological regulations but remains challenging. Previously, we introduced the micro-scaffold assisted spatial proteomics (MASP) concept for whole-tissue mapping. However, this prototype required substantial development in spatial resolution, practicality, and throughput for practical application. Here we present a next-generation MASP technique (hex-MASP) featuring i) a new design of hexagonal-micro-wells fabricated with optimized projection micro-stereolithography 3D-printing, achieving high spatial resolution, sampling robustness, and mechanical strength for reproducibly compartmentalizing even tough tissues; ii) enhanced throughput/effectiveness in sample preparation and LC–MS analysis with high quantitative quality. Applied to mouse brain, hex-MASP achieved in-depth, whole-tissue mapping for >6,000 proteins in mouse brains, with high spatial accuracy and excellent data quality. The substantially improved resolution revealed critical regional details across the entire brain, that were not previously captured, enabling precise depiction of protein distribution heterogeneity. This technique enabled the identification of many unreported regionally enriched proteins across brain structures. We further applied hex-MASP to investigate the intrabrain distribution of intracerebroventricularly dosed antibody therapeutics and related proteins, which enabled whole-tissue mapping of protein drugs revealed insights into antibody brain penetration and distribution. Hex-MASP represents a robust, scalable platform for whole-tissue spatial proteomics.

生物化学工学
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