一种高亲和力、高浓度的生物工程抗血管内皮生长因子蛋白,用于玻璃体内治疗湿性老年性黄斑变性

IF 6.1 2区 医学 Q1 ENGINEERING, BIOMEDICAL Bioengineering & Translational Medicine Pub Date : 2023-12-19 DOI:10.1002/btm2.10632
Chengnan Huang, Yuelin Wang, Jinliang Huang, Huiqin Liu, Zhidong Chen, Yang Jiang, Youxin Chen, Feng Qian
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引用次数: 0

摘要

抗血管内皮生长因子(anti-VEGF)的玻璃体内注射(IVT)大大改善了许多视网膜疾病的治疗,包括湿性年龄相关性黄斑变性(wAMD),它是导致失明的第三大原因。然而,频繁注射会给患者带来困难,并可能导致眼压升高、感染和视网膜脱离等各种风险。为解决这一问题,研究人员发现,以最大可行浓度和剂量静脉注射抗血管内皮生长因子蛋白是一种有效的策略。然而,由于稳定性和溶液粘度的原因,蛋白质的固有结构会限制最大浓度。为了克服这一难题,我们通过将抗血管内皮生长因子纳米抗体与可结晶片段(Fc)融合,开发出了一种名为 nanoFc 的新型抗血管内皮生长因子蛋白。NanoFc 在各种生物测定中通过多价性和强效生物活性证明了与 VEGF165 的高结合亲和力。此外,nanoFc 还能在 4°C 温度下保持令人满意的化学和物理稳定性达 1 个月之久,而且由于其独特的结构产生了较小的形状系数,因此注射浓度高达 200 mg/mL,注射十分方便。nanoFc 的设计提供了一种生物工程策略,既能确保较强的抗 VEGF 结合亲和力,又能确保较高的蛋白质浓度,从而达到减少静脉注射次数的目的。
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A bioengineered anti-VEGF protein with high affinity and high concentration for intravitreal treatment of wet age-related macular degeneration

Intravitreal (IVT) injection of anti-vascular endothelial growth factor (anti-VEGF) has greatly improved the treatment of many retinal disorders, including wet age-related macular degeneration (wAMD), which is the third leading cause of blindness. However, frequent injections can be difficult for patients and may lead to various risks such as elevated intraocular pressure, infection, and retinal detachment. To address this issue, researchers have found that IVT injection of anti-VEGF proteins at their maximally viable concentration and dose can be an effective strategy. However, the intrinsic protein structure can limit the maximum concentration due to stability and solution viscosity. To overcome this challenge, we developed a novel anti-VEGF protein called nanoFc by fusing anti-VEGF nanobodies with a crystallizable fragment (Fc). NanoFc has demonstrated high binding affinity to VEGF165 through multivalency and potent bioactivity in various bioassays. Furthermore, nanoFc maintains satisfactory chemical and physical stability at 4°C over 1 month and is easily injectable at concentrations up to 200 mg/mL due to its unique architecture that yields a smaller shape factor. The design of nanoFc offers a bioengineering strategy to ensure both strong anti-VEGF binding affinity and high protein concentration, with the goal of reducing the frequency of IV injections.

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来源期刊
Bioengineering & Translational Medicine
Bioengineering & Translational Medicine Pharmacology, Toxicology and Pharmaceutics-Pharmaceutical Science
CiteScore
8.40
自引率
4.10%
发文量
150
审稿时长
12 weeks
期刊介绍: Bioengineering & Translational Medicine, an official, peer-reviewed online open-access journal of the American Institute of Chemical Engineers (AIChE) and the Society for Biological Engineering (SBE), focuses on how chemical and biological engineering approaches drive innovative technologies and solutions that impact clinical practice and commercial healthcare products.
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