遗传编码荧光探针在疾病诊断中的最新进展

李睿; 左方婷; 杨弋

doi:10.12211/2096-8280.2025-045

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遗传编码荧光探针在疾病诊断中的最新进展

特约评述 | 更新时间：2026-03-07

- 遗传编码荧光探针在疾病诊断中的最新进展
- Recent advances in genetically encoded fluorescent sensors for disease diagnosis
- 合成生物学 2026年7卷第1期页码：102-112
- 作者机构：
  
  1.华东理工大学光遗传学与合成生物学跨学科研究中心，生物反应器工程国家重点实验室，上海 200237
  2.华东理工大学药学院，上海市细胞代谢光遗传学技术前沿科学研究基地，上海 200237
  3.南方医科大学深圳医院，广东深圳 518110
  4.同济大学附属杨浦医院，上海 200090
- 作者简介：
  
  [ "李睿（1996—），女，博士研究生。研究方向为合成生物技术与生物传感技术结合在监测细胞内实时动态代谢过程。 E-mail： y20180020@mail.ecust.edu.cn" ]
  [ "杨弋（1973—），男，教授,博士生导师。主要研究方向为利用合成生物技术与光遗传学技术控制与监测细胞内分子过程的前沿技术；癌症及代谢类疾病药理及药物筛选技术；蛋白质特异性标记、翻译后修饰的鉴定、与细胞内原位成像；蛋白质药物生产技术等。E-mail： yiyang@ecust.edu.cn" ]
- 基金信息：
  
  国家重点研发计划“基因表达时空精准操控技术研究”(2022YFC3400100);国家自然科学基金-创新研究群体项目“细胞代谢监测与调控”(32121005);上海市青年科技英才扬帆计划“近红外荧光RNA的开发与应用研究”(24YF2709300);博士后创新人才支持计划“基于新型胆汁酸生物传感器在肠道菌群中时空动态监测与调控”
- DOI：10.12211/2096-8280.2025-045
  中图分类号： Q816
- 收稿：2025-05-13，
  
  修回：2025-08-28，
  
  纸质出版：2026-02-28
- 稿件说明：
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李睿，左方婷，杨弋. 遗传编码荧光探针在疾病诊断中的最新进展［J］. 合成生物学， 2026， 7（1）： 102-112

LI Rui， ZUO Fangting， YANG Yi. Recent advances in genetically encoded fluorescent sensors for disease diagnosis［J］. Synthetic Biology Journal， 2026， 7（1）： 102-112
李睿，左方婷，杨弋. 遗传编码荧光探针在疾病诊断中的最新进展［J］. 合成生物学， 2026， 7（1）： 102-112 DOI： 10.12211/2096-8280.2025-045.

LI Rui， ZUO Fangting， YANG Yi. Recent advances in genetically encoded fluorescent sensors for disease diagnosis［J］. Synthetic Biology Journal， 2026， 7（1）： 102-112 DOI： 10.12211/2096-8280.2025-045.

摘要

近年来，遗传编码荧光探针在结构优化与疾病诊断应用中取得了快速发展。通过蛋白质工程，荧光蛋白在光稳定性、灵敏度和光谱范围方面显著提升，并涌现出多种新型传感机制，实现了离子、代谢物及神经递质等生理信号的实时可视化。与此同时，荧光RNA在折叠稳定性、激活效率和亮度上不断突破，多色工具箱的建立使 RNA 动态成像成为可能。这两类探针已广泛应用于肿瘤代谢、糖尿病及神经疾病研究，在代谢监测、病理状态识别和早期诊断等方面展现出独特优势，推动了疾病机制解析与诊断技术进步。未来，随着探针性能持续优化和设计创新，遗传编码荧光探针有望在基础研究和临床转化中发挥更大作用，为精准诊断和个性化医疗提供有力支持。

Abstract

In recent years

significant advances have been made in genetically encoded fluorescent sensors. Fluorescent protein-based sensors have seen continuous improvements in performance

with researchers employing protein engineering techniques to develop brighter and more photostable fluorescent protein variants

as well as extending their emission spec

tra into the far-red region for deeper tissue imaging. Concurrently

innovative sensing mechanisms have emerged

such as the incorporation of genetically encoded unnatural fluorescent amino acids to construct miniaturized fluorescent reporter molecules

and strategies utilizing protein conformational changes or Förster resonance energy transfer (FRET) to sensitively detect biological signals. Researchers have also developed highly specific fluorescent sensors targeting particular biomarkers

including genetically encoded sensors for detecting ions

metabolites

or enzyme activities

providing powerful tools for precise monitoring of cellular physiological processes. Meanwhile

RNA fluorescent aptamers

another major category of genetically encoded sensors

have achieved substantial progress in structural optimization and functional expansion. Newly screened and engineered fluorescent aptamers exhibit enhanced affinity and specificity toward their fluorescent ligands

significantly improving fluorescence activation efficiency. Certain aptamer-ligand complexes now exhibit brightness comparable to

or even exceeding

traditional fluorescent proteins. Various combinations of aptamers and fluorophores currently cover emission spectra ranging from visible to near-infrared. These RNA-based sensors have successfully enabled the labeling and visualization of endogenous RNA molecules in living cells

facilitating real-time tracking of RNA localization and dynamics. Furthermore

combining fluorescent aptamers with small-molecule recognition aptamers has enabled the creation of novel fluorescent “switch” sensors

whose fluorescence is activated through conformational changes triggered by the presence of specific metabolites. Both types of genetically encoded sensors demonstrate substantial values in disease diagnosis. For instance

fluorescent protein-based biosensors can monitor abnormal fluctuations of intracellular metabolites and signaling molecules

such as glucose or ATP levels

aiding in the elucidation of metabolic c

haracteristics in diseases like diabetes and cancers. Utilizing improved near-infrared fluorescent proteins and fluorescent aptamers

in vivo

allows deeper tissue penetration and facilitates early detection of pathological changes

such as tumors. Additionally

fluorescent sensors specifically designed for pathological states-such as oxidative stress

pH imbalance

or particular enzyme activities—can directly report disease signals at the cellular level

supporting precise diagnostics. Overall

these advancements significantly enhance the sensitivity and specificity of biological imaging and molecular diagnostics. Looking forward

as sensor performance continues to improve and new sensing principles emerge

genetically encoded fluorescent sensors will increasingly play prominent roles in more complex biological systems and clinical diagnostics

exhibiting tremendous potentials for future applications.

关键词

Keywords

references

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