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.
{"title":"A bioengineered anti-VEGF protein with high affinity and high concentration for intravitreal treatment of wet age-related macular degeneration","authors":"Chengnan Huang, Yuelin Wang, Jinliang Huang, Huiqin Liu, Zhidong Chen, Yang Jiang, Youxin Chen, Feng Qian","doi":"10.1002/btm2.10632","DOIUrl":"10.1002/btm2.10632","url":null,"abstract":"<p>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 VEGF<sub>165</sub> 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.</p>","PeriodicalId":9263,"journal":{"name":"Bioengineering & Translational Medicine","volume":null,"pages":null},"PeriodicalIF":7.4,"publicationDate":"2023-12-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/btm2.10632","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138823284","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Yannick Rösch, Thorald Stolte, Miriam Weisskopf, Sabrina Frey, Rob Schwartz, Nikola Cesarovic, Dominik Obrist
Microvascular obstruction (MVO) often occurs in ST-elevation myocardial infarction (STEMI) patients after percutaneous coronary intervention (PCI). Diagnosis and treatment of MVO lack appropriate and established procedures. This study focused on two major points by using an in vitro multiscale flow model, which comprised an aortic root model with physiological blood flow and a microfluidic model of the microcirculation with vessel diameters down to 50 μm. First, the influence of porcine microthrombi (MT), injected into the fluidic microchip, on perfusion was investigated. We found that only