arXiv:2507.19568cs.CYcs.AI2025-07

用AI构建可编程虚拟人,实现体内药物测试新范式

Programmable Virtual Humans Toward Human Physiologically-Based Drug Discovery

  • 基于多尺度数据构建动态虚拟人体模型
  • 实现从分子到表型的药物作用全程模拟
  • 适合早期药物研发与安全评估团队使用

人工智能在药物发现中引发广泛关注,但现有方法仅数字化高通量实验,仍受限于传统流程,无法解决预测药物在人体中效应的根本难题。生物医学数字孪生虽基于真实数据与机制模型,却多用于后期开发,难以刻画分子相互作用及其系统性后果,限制其在早期发现中的应用。这种早期与后期之间的脱节正是药物研发高失败率的主要原因。真正的突破在于让AI不仅增强现有实验,更实现现实中不可能的虚拟实验:直接在体外模拟药物在人体内的作用。当前AI进展、高通量扰动检测及跨物种单细胞与空间组学技术的发展,使构建可编程虚拟人成为可能——即能从分子到表型层面动态模拟药物行为的多尺度模型。通过弥合转化鸿沟,这类模型为更早优化治疗效果与安全性提供了变革路径。本文提出可编程虚拟人的概念,探讨其在以人体生理为核心的新药物发现范式中的角色,并梳理关键机遇、挑战与实现路线图。

原文摘要 · Abstract (English)

Artificial intelligence (AI) has sparked immense interest in drug discovery, but most current approaches only digitize existing high-throughput experiments. They remain constrained by conventional pipelines. As a result, they do not address the fundamental challenges of predicting drug effects in humans. Similarly, biomedical digital twins, largely grounded in real-world data and mechanistic models, are tailored for late-phase drug development and lack the resolution to model molecular interactions or their systemic consequences, limiting their impact in early-stage discovery. This disconnect between early discovery and late development is one of the main drivers of high failure rates in drug discovery. The true promise of AI lies not in augmenting current experiments but in enabling virtual experiments that are impossible in the real world: testing novel compounds directly in silico in the human body. Recent advances in AI, high-throughput perturbation assays, and single-cell and spatial omics across species now make it possible to construct programmable virtual humans: dynamic, multiscale models that simulate drug actions from molecular to phenotypic levels. By bridging the translational gap, programmable virtual humans offer a transformative path to optimize therapeutic efficacy and safety earlier than ever before. This perspective introduces the concept of programmable virtual humans, explores their roles in a new paradigm of drug discovery centered on human physiology, and outlines key opportunities, challenges, and roadmaps for their realization.

虚拟人药物发现AI制药多尺度建模

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