合成生物学策略下的人工血液研究进展

doi:10.12211/2096-8280.2025-094

合成生物学

• 特约评述 •

合成生物学策略下的人工血液研究进展

黄如平¹, 孙文钊¹, 金娟¹, 吕雪丽², 盛静逸³, 黄斌¹, 顾宁¹^,³^,⁴

^1. 南京医科大学生物医学工程与信息学院，江苏省生物医学电磁精准诊疗重点实验室，江苏南京 210029
^2. 南京大学医学院附属鼓楼医院临床医学研究院，江苏省血管信息与健康工程医学重点实验室，江苏南京 210008
^3. 东南大学生物科学与医学工程学院，江苏省生物材料与器件重点实验室，江苏南京 210096
^4. 南京大学医学院工程医学研究组，南京生物与医学电子显微技术研究中心，江苏南京 210093

收稿日期:2025-10-11 修回日期:2025-11-12 出版日期:2025-11-17
通讯作者: 黄斌,顾宁
作者简介:黄如平（2002—），女，硕士研究生。研究方向为细胞膜仿生材料的制备与应用。E-mail：18260480971@163.com
黄斌（1980—），男，博士，副教授，硕士生导师，中国化学会会员，研究方向为生物医学材料及诊疗应用。主持国家自然科学基金面上项目、国家重点研发计划项目子课题等纵向科研项目8项。E-mail：huangbinhb31@njmu.edu.cn
顾宁（1964—），男，博士，博士生导师，中国科学院院士，南京市血管信息与健康工程医学重点实验室主任，现任南京大学医学院教授。研究方向为分子功能材料薄膜、纳米加工以及纳米材料制备、表征及其在生物医（药）学领域中的应用，完成并正在承担多项国家级及部省级科研项目。E-mail：guning@nju.edu.cn
基金资助:
国家重点研发计划(2023YFF0713600);国家自然科学基金(62375138);江苏省重大科技基础设施预研项目

Synthetic biology-driven advances in artificial blood research

HUANG Ruping¹, SUN Wenzhao¹, JIN Juan¹, LV Xueli², SHENG Jingyi³, HUANG Bin¹, GU Ning¹^,³^,⁴

^1. Jiangsu Key Laboratory for Biomedical Electromagnetic Precision Theranostics，School of Biomedical Engineering and Informatics，Nanjing Medical University，Nanjing 210029，Jiangsu，China
^2. Jiangsu Key Laboratory for Cardiovascular Information and Health Engineering Medicine，Institute of Clinical Medicine，Affiliated Drum Tower Hospital，Medical School of Nanjing University，Nanjing 210008，Jiangsu，China
^3. Jiangsu Key Laboratory for Biomaterials and Devices，School of Biological Science and Medical Engineering，Southeast University，Nanjing 210096，Jiangsu，China
^4. Engineering Medicine Research Group，and Nanjing Research Center for Biomedical Electron Microscopy，Nanjing University，Nanjing 210093，Jiangsu，China

Received:2025-10-11 Revised:2025-11-12 Online:2025-11-17
Contact: HUANG Bin, GU Ning

摘要/Abstract

摘要：

人工血液是一类具有载氧能力、可替代血液部分功能的液体制剂，其研发旨在缓解对献血供给的依赖，以应对血液供应不足及输血风险隐患。近年来，随着合成生物学技术的突破，人工血液主要成分如红细胞、血小板和血浆等在功能重构与系统集成方面取得了显著进展。本文基于合成生物学视角，系统阐述人工血液主要成分的构建策略与研究进展。在人工红细胞方面，通过血红蛋白结构优化、血红素合成通路重构及仿生膜封装，显著提升携氧效率和体内稳定性；在人工血小板方面，通过干细胞编程与基因编程，血小板生成效率显著提高；在人工血浆方面，通过核心功能蛋白表达优化与多功能融合蛋白设计，为实现稳定的血容量维持以及免疫支持提供可能性。最后，本文探讨了当前人工血液研究面临的挑战与未来发展方向。目前，人工血液的研究仍主要聚焦于单一功能模块的构建，且在生物相容性、长期稳定性、规模化制备及质量标准体系建设等方面存在诸多瓶颈。未来，可借助合成生物学的模块化设计理念与人工智能辅助，整合红细胞、血小板及血浆等关键功能模块，推动人工血液研究的临床转化，从而为开发更安全、高效的新一代血液替代品提供重要支撑。

关键词: 人工血液, 合成生物学, 人工红细胞, 人工血小板, 血浆替代品

Abstract:

Artificial blood refers to oxygen-carrying liquid formulations that can partially substitute the functions of natural blood. Its development seeks to lessen reliance on donor supplies, alleviate shortages, and reduce transfusion-related risks. In recent years, advances in synthetic biology have driven notable progress in both the functional reconstruction and the systems-level integration of the principal components of artificial blood—red blood cells, platelets, and plasma. Taking a synthetic-biology perspective, this review summarizes construction strategies and recent advances across these modules.For artificial red blood cells, three complementary strategies have proven highly effective: the rational optimization of hemoglobin structure, the reconstruction of heme-biosynthetic pathways to balance cofactor supply with globin expression, and biomimetic membrane encapsulation. Together, these strategies enhance oxygen-delivery efficiency and improve in vivo stability. In the platelet module, stem-cell programming and gene programming have markedly increased production efficiency, offering a path toward more controllable and scalable sources that are independent of donor availability. For artificial plasma, optimizing the expression of core functional proteins and designing multifunctional fusion proteins provide new possibilities for maintaining circulating volume and supporting immune function.The review also discusses the key challenges that currently limit translation. Present research remains largely focused on single functional modules, and substantial bottlenecks persist in biocompatibility, long-term stability, large-scale manufacturing, and the establishment of robust quality-standards systems. Addressing these gaps will require standardized evaluation criteria spanning safety, potency, and stability, alongside reproducible processes suitable for clinical-grade production. In the future, the field can leverage modular design principles in combination with artificial-intelligence assistance to integrate red-cell, platelet, and plasma functions into coherent, programmable architectures. Such integrative strategies are expected to accelerate the pathway from laboratory concepts to clinical applications and to support the development of safer and more effective next-generation blood substitutes. By integrating synthetic-biology toolkits with rigorous quality control and scalable production, artificial blood research is poised for clinical translation. This progress promises practical solutions for oxygen transport, volume maintenance, and immune support in settings with limited blood supplies or high transfusion risks.

Key words: artificial blood, synthetic biology, artificial red blood cells, artificial platelets, plasma substitutes

中图分类号:

R977.8

黄如平, 孙文钊, 金娟, 吕雪丽, 盛静逸, 黄斌, 顾宁. 合成生物学策略下的人工血液研究进展[J]. 合成生物学, DOI: 10.12211/2096-8280.2025-094.

HUANG Ruping, SUN Wenzhao, JIN Juan, LV Xueli, SHENG Jingyi, HUANG Bin, GU Ning. Synthetic biology-driven advances in artificial blood research[J]. Synthetic Biology Journal, DOI: 10.12211/2096-8280.2025-094.

图/表 4

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名称	构成	功能	研究进展
HemAssist ^[14]	2,3-二阿司匹林交联血红蛋白	急救输血扩容兼携氧	1999年未通过三期试验
PolyHeme ^[15]	吡哆醛磷酸盐交联戊二醛血红蛋白	紧急氧供应	2009在美国完成III期试验，但没有获得FDA批准
Hemolink ^[16]	O-棉子糖交联血红蛋白	即时携氧与扩容支持	已通过三期临床；已停止研究
Hemospan ^[17]	马来酰亚胺修饰的聚乙二醇化人血红蛋白	维持组织氧合减少血管收缩	已通过三期临床；2015年停止开发
Hemoximer ^[18]	共轭的磷酸化血红蛋白/交联的人血红蛋白	高效携氧与NO清除适应低温和极端环境	三期临床于2011年终止
Hemopure ^[19]	戊二醛聚合牛血红蛋白	手术贫血治疗无需血型匹配	III期临床试验完成并批准在南非和俄罗斯用于人体试验
OxyVita ^[20]	聚合牛血红蛋白	减少血管渗漏	临床试验进行中；研究进行中
Sanguinate^[21]	聚乙二醇化羧基血红蛋白	用于镰状细胞病和缺血性疾病	未通过三期临床，研究进行中
Synthoplate^{TM [22]}	脂质体共价修饰三类功能肽：RGD肽（聚集）、vWF肽（黏附）、胶原肽（定位）	可快速止血	在多动物模型中验证止血效果良好，正推进临床前安全性评估

名称	构成	功能	研究进展
HemAssist ^[14]	2,3-二阿司匹林交联血红蛋白	急救输血扩容兼携氧	1999年未通过三期试验
PolyHeme ^[15]	吡哆醛磷酸盐交联戊二醛血红蛋白	紧急氧供应	2009在美国完成III期试验，但没有获得FDA批准
Hemolink ^[16]	O-棉子糖交联血红蛋白	即时携氧与扩容支持	已通过三期临床；已停止研究
Hemospan ^[17]	马来酰亚胺修饰的聚乙二醇化人血红蛋白	维持组织氧合减少血管收缩	已通过三期临床；2015年停止开发
Hemoximer ^[18]	共轭的磷酸化血红蛋白/交联的人血红蛋白	高效携氧与NO清除适应低温和极端环境	三期临床于2011年终止
Hemopure ^[19]	戊二醛聚合牛血红蛋白	手术贫血治疗无需血型匹配	III期临床试验完成并批准在南非和俄罗斯用于人体试验
OxyVita ^[20]	聚合牛血红蛋白	减少血管渗漏	临床试验进行中；研究进行中
Sanguinate^[21]	聚乙二醇化羧基血红蛋白	用于镰状细胞病和缺血性疾病	未通过三期临床，研究进行中
Synthoplate^{TM [22]}	脂质体共价修饰三类功能肽：RGD肽（聚集）、vWF肽（黏附）、胶原肽（定位）	可快速止血	在多动物模型中验证止血效果良好，正推进临床前安全性评估

工具类型	核心原理	优势	局限性	参考文献
基因编辑与调控系统	利用 Cas 核酸酶对目标 DNA 精确切割与修复，实现基因定点插入或敲除	高精度、可编程、可实现多基因并行调控	潜在脱靶风险、伦理限制	[37]
底盘细胞与代谢工程	通过基因组与代谢优化，重构宿主的生产能力与安全性	支持多模块组合与迭代优化，实现高效生物合成	代谢负担大，调控复杂	[38]
无细胞与人工系统构建	通过细胞提取或纯化组分体系在体外重建转录翻译与代谢反应，实现蛋白合成与人工细胞构建	高可控性、模块化、支持多回路测试与人工细胞构建	能量维持时间短、体系成本高、缺乏自我复制与长期稳态	[39, 40]
AI与自动化DBTL循环	将机器学习嵌入DBTL循环，实现实验预测与迭代优化	加速设计迭代、提升预测精度、多变量优化，减少成本	需大规模数据支撑	[41]

工具类型	核心原理	优势	局限性	参考文献
基因编辑与调控系统	利用 Cas 核酸酶对目标 DNA 精确切割与修复，实现基因定点插入或敲除	高精度、可编程、可实现多基因并行调控	潜在脱靶风险、伦理限制	[37]
底盘细胞与代谢工程	通过基因组与代谢优化，重构宿主的生产能力与安全性	支持多模块组合与迭代优化，实现高效生物合成	代谢负担大，调控复杂	[38]
无细胞与人工系统构建	通过细胞提取或纯化组分体系在体外重建转录翻译与代谢反应，实现蛋白合成与人工细胞构建	高可控性、模块化、支持多回路测试与人工细胞构建	能量维持时间短、体系成本高、缺乏自我复制与长期稳态	[39, 40]
AI与自动化DBTL循环	将机器学习嵌入DBTL循环，实现实验预测与迭代优化	加速设计迭代、提升预测精度、多变量优化，减少成本	需大规模数据支撑	[41]

合成生物学策略下的人工血液研究进展

Synthetic biology-driven advances in artificial blood research

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