生物技术通报 ›› 2023, Vol. 39 ›› Issue (12): 118-127.doi: 10.13560/j.cnki.biotech.bull.1985.2023-0289
钟朝滨1(), 朱龙佼2, 张博洋2, 张洋子1, 陈可仁1, 许文涛2()
收稿日期:
2023-03-29
出版日期:
2023-12-26
发布日期:
2024-01-11
通讯作者:
许文涛,男,博士,教授,研究方向:功能核酸生物传感器;E-mail: xuwentao@cau.edu.cn作者简介:
钟朝滨,男,硕士研究生,研究方向:营养与食品安全;E-mail: zhaobin97@139.com
基金资助:
ZHONG Zhao-bin1(), ZHU Long-jiao2, ZHANG Bo-yang2, ZHANG Yang-zi1, CHEN Ke-ren1, XU Wen-tao2()
Received:
2023-03-29
Published:
2023-12-26
Online:
2024-01-11
摘要:
核酸适配体是由20-100个核苷酸组成的单链脱氧核糖核酸(ssDNA)或核糖核酸(RNA),一般是通过指数富集的配体系统进化技术(SELEX)进行筛选。核酸适配体可以与多种靶标物质特异性结合,包括毒素、金属离子、生物大分子、微生物等,已被广泛应用于食品检测、医疗诊断等领域。细胞作为人体最基本的组成单位是大多数疾病病理机制和治疗策略的研究重心。近年来,核酸疗法以更安全更高效的优势成为疾病治疗领域的研究重心,研究人员认识到核酸适配体的靶向结合能力可以应用到细胞的靶向治疗中。因此,开发出Cell-SELEX技术用于筛选可以靶向细胞标志物的核酸适配体。细胞特异性核酸适配体与传统的核酸适配体的区别,在于它们的特异性靶标是细胞成分,它们可以直接结合与细胞生长和代谢相关的物质影响细胞生理活动,也可以作为靶向递送工具递送药物,在疾病的精准治疗中具有突破性影响。因此,细胞特异性核酸适配体引发了广泛关注。本文对细胞特异性核酸适配体在多种疾病治疗中的研究进展进行了综述,以期为其在人类疾病治疗中的应用提供参考。
钟朝滨, 朱龙佼, 张博洋, 张洋子, 陈可仁, 许文涛. 细胞特异性核酸适配体在疾病治疗中的应用[J]. 生物技术通报, 2023, 39(12): 118-127.
ZHONG Zhao-bin, ZHU Long-jiao, ZHANG Bo-yang, ZHANG Yang-zi, CHEN Ke-ren, XU Wen-tao. Application of Cell-specific Nucleic Acid Aptamers in Disease Treatment[J]. Biotechnology Bulletin, 2023, 39(12): 118-127.
核酸适配体 Nucleic acid aptamer | 靶标 Target | 疾病 Disease | 临床阶段 Clinical phase | 用药方式 Medication administration | ClinicalTrials.gov标识符 ClinicalTrials.gov identifier |
---|---|---|---|---|---|
Macugen | VEGF | 年龄相关性黄斑变性 | 已上市 | 玻璃体内注射 | NCT01573572 |
E10030(Fovista) | PDGF | 新生血管性年龄相关性黄斑变性 | 临床III期 | 玻璃体内注射 | NCT01944839 |
ARC1905(Zimura) | C5 | 年龄相关性黄斑变性 | 临床II期 | 玻璃体内注射 | NCT03364153 |
REG1 | 凝血因子IXa | 冠状动脉疾病 | 临床II期 | 静脉注射 | NCT00715455 |
ARC1779 | 血管性血友病因子A1结构域 | 急性心肌梗死 | 临床II期 | - | NCT00507338 |
NU172 | 凝血酶 | 心脏病 | 临床II期 | 冠状动脉旁路移植术中静脉推注后持续输注 | NCT00808964 |
AS1411(AGRO001) | 核仁素 | 原发性难治或复发急性髓系白血病 | 临床II期 | - | NCT01034410 |
NOX-A12 | CXCL12/SDF-1 | 慢性淋巴细胞白血病 | 临床II期 | - | NCT01486797 |
NOX-E36 | CCL2/MCP-1 | 2型糖尿病;蛋白尿 | 临床II期 | 皮下注射 | NCT01547897 |
NOX-H94 | 铁调素 | 慢性病贫血 | 临床II期 | 静脉注射 | NCT01691040 |
BAX499(ARC19499) | 组织因子途径抑制物(TFPI) | 血友病 | 临床I期 | 注射 | NCT01191372 |
表1 进入临床试验中的核酸适配体
Table 1 Nucleic acid aptamers entering clinical trials
核酸适配体 Nucleic acid aptamer | 靶标 Target | 疾病 Disease | 临床阶段 Clinical phase | 用药方式 Medication administration | ClinicalTrials.gov标识符 ClinicalTrials.gov identifier |
---|---|---|---|---|---|
Macugen | VEGF | 年龄相关性黄斑变性 | 已上市 | 玻璃体内注射 | NCT01573572 |
E10030(Fovista) | PDGF | 新生血管性年龄相关性黄斑变性 | 临床III期 | 玻璃体内注射 | NCT01944839 |
ARC1905(Zimura) | C5 | 年龄相关性黄斑变性 | 临床II期 | 玻璃体内注射 | NCT03364153 |
REG1 | 凝血因子IXa | 冠状动脉疾病 | 临床II期 | 静脉注射 | NCT00715455 |
ARC1779 | 血管性血友病因子A1结构域 | 急性心肌梗死 | 临床II期 | - | NCT00507338 |
NU172 | 凝血酶 | 心脏病 | 临床II期 | 冠状动脉旁路移植术中静脉推注后持续输注 | NCT00808964 |
AS1411(AGRO001) | 核仁素 | 原发性难治或复发急性髓系白血病 | 临床II期 | - | NCT01034410 |
NOX-A12 | CXCL12/SDF-1 | 慢性淋巴细胞白血病 | 临床II期 | - | NCT01486797 |
NOX-E36 | CCL2/MCP-1 | 2型糖尿病;蛋白尿 | 临床II期 | 皮下注射 | NCT01547897 |
NOX-H94 | 铁调素 | 慢性病贫血 | 临床II期 | 静脉注射 | NCT01691040 |
BAX499(ARC19499) | 组织因子途径抑制物(TFPI) | 血友病 | 临床I期 | 注射 | NCT01191372 |
疾病类型 Disease type | 代表性适配体药物 Representative aptamer drugs | 药物类型 Types of drugs | 靶标 Targets |
---|---|---|---|
癌症 | AB3-Dox | 核酸适配体-药物偶联物(ApDCs) | 未成熟层黏连蛋白受体蛋白(OFA/iLRP) |
sgc8c-Dox | 蛋白酪氨酸激酶7(PTK7) | ||
AS1411适配体偶联脂质体 | 核酸适配体-siRNA缀合物 | 结直肠癌细胞 | |
MUC1适配体-CD16适配体 | 双特异性核酸适配体 | MUC1阳性肿瘤细胞和CD16阳性淋巴细胞 | |
ApEn-NK | 核酸适配体工程自然杀伤细胞 | 多种肿瘤细胞 | |
组织修复与再生 | GO-SA凝胶-适配体-GBF | 骨髓间充质干细胞核酸适配体支架 | 骨髓间充质干细胞(BM-MSCs) |
眼部疾病 | Macugen | 核酸适配体 | VEGF |
E10030 | PDGF | ||
ARC1905 | 补体成分5(C5) | ||
脑部疾病 | SYL3C-GS24 | 双功能核酸适配体 | 转铁蛋白受体(TfR) |
血管疾病 | REG1 | 核酸适配体 | 凝血因子IXa |
ARC1779 | 血管性血友病因子(VWF)A1结构域 | ||
BAX499 | 组织因子通路抑制剂(TFPI) | ||
NU172 | G-四链体DNA核酸适配体 | 凝血酶 | |
炎症疾病 | VR11功能化单层石墨烯 | 核酸适配体纳米传感器(用于检测) | TNFα |
NOX-E36 | 核酸适配体 | 趋化因子配体2(CCL 2) | |
NOX-H94 | 铁调素 |
表2 不同疾病治疗中开发的核酸适配体的应用
Table 2 Applications of nucleic acid aptamers developed in the treatment of different diseases
疾病类型 Disease type | 代表性适配体药物 Representative aptamer drugs | 药物类型 Types of drugs | 靶标 Targets |
---|---|---|---|
癌症 | AB3-Dox | 核酸适配体-药物偶联物(ApDCs) | 未成熟层黏连蛋白受体蛋白(OFA/iLRP) |
sgc8c-Dox | 蛋白酪氨酸激酶7(PTK7) | ||
AS1411适配体偶联脂质体 | 核酸适配体-siRNA缀合物 | 结直肠癌细胞 | |
MUC1适配体-CD16适配体 | 双特异性核酸适配体 | MUC1阳性肿瘤细胞和CD16阳性淋巴细胞 | |
ApEn-NK | 核酸适配体工程自然杀伤细胞 | 多种肿瘤细胞 | |
组织修复与再生 | GO-SA凝胶-适配体-GBF | 骨髓间充质干细胞核酸适配体支架 | 骨髓间充质干细胞(BM-MSCs) |
眼部疾病 | Macugen | 核酸适配体 | VEGF |
E10030 | PDGF | ||
ARC1905 | 补体成分5(C5) | ||
脑部疾病 | SYL3C-GS24 | 双功能核酸适配体 | 转铁蛋白受体(TfR) |
血管疾病 | REG1 | 核酸适配体 | 凝血因子IXa |
ARC1779 | 血管性血友病因子(VWF)A1结构域 | ||
BAX499 | 组织因子通路抑制剂(TFPI) | ||
NU172 | G-四链体DNA核酸适配体 | 凝血酶 | |
炎症疾病 | VR11功能化单层石墨烯 | 核酸适配体纳米传感器(用于检测) | TNFα |
NOX-E36 | 核酸适配体 | 趋化因子配体2(CCL 2) | |
NOX-H94 | 铁调素 |
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