Continuous Suppression of Pathological Retinal and Choroidal Neovascularization in Cynomolgus Monkeys via Noninvasive Ophthalmic Delivery of a Novel Anti-VEGFA Nanobody and Proprietary Penetratin Analog Formulation
文献类型：期刊论文
| 作者 | Chen, Chong1; Zhu, Min2; Fan, Xingyan3; Lv, Kangjia1; Jiang, Kuan3,4,5; Zhang, Yuchen1; Zhang, Haoliang1; Qi, Xinming6; Lee, Benjamin T. K.7; Wan, Yakun2 |
| 刊名 | ADVANCED SCIENCE
 |
| 出版日期 | 2025-10-21 |
| 页码 | 13 |
| 关键词 | age-related macular degeneration cell-penetrating peptides diabetic retinopathy nanobody neovascularization noninvasive intraocular delivery single-domain antibody |
| DOI | 10.1002/advs.202504660 |
| 英文摘要 | Pathological retinal and choroidal neovascularization is a hallmark of several blinding diseases, including diabetic retinopathy and age-related macular degeneration. While intravitreal anti-VEGF therapies remain the standard of care, they necessitate frequent injections, posing risks such as endophthalmitis and elevated intraocular pressure, alongside economic and adherence challenges. Here, we present Pene/LQ015, a novel eye drop formulation comprising the anti-VEGFA nanobody (LQ015) and a proprietary penetratin analog for noninvasive delivery. LQ015 demonstrates superior VEGF-blocking activity, broad binding specificity across species, and robust stability and scalability using a yeast expression system. Topical administration of Pene/LQ015 achieved effective retinal-choroid complex drug levels and suppressed neovascularization in preclinical models. Notably, in the cynomolgus monkey laser-induced choroidal neovascularization model, 30 days of continuous topical application significantly reduced neovascularization and vascular leakage, with excellent safety and tolerability. These findings highlight Pene/LQ015's potential as a game-changer in treating neovascular eye diseases. It offers a groundbreaking, noninvasive alternative to intravitreal injections, addressing key limitations of current therapies by enabling continuous dosing, improving patient adherence, and reducing treatment burden. These findings underscore its potential to transform the management of neovascular retinal and choroidal diseases, with promising implications for clinical application. |
| WOS关键词 | INTRAVITREAL INJECTION ; PEPTIDE ; RETINOPATHY ; MODEL |
| 资助项目 | Lumitin Vision to Brightness Research Funding |
| WOS研究方向 | Chemistry ; Science & Technology - Other Topics ; Materials Science |
| 语种 | 英语 |
| WOS记录号 | WOS:001597692700001 |
| 出版者 | WILEY |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/320727]  |
| 专题 | 国家级研究中心_原创新药研究全国重点实验室 |
| 通讯作者 | Lee, Benjamin T. K.; Wan, Yakun; Wei, Gang; Liu, Kun; Xu, Xun |
| 作者单位 | 1.Shanghai Jiao Tong Univ, Shanghai Gen Hosp, Natl Clin Res Ctr Eye Dis, Sch Med,Shanghai Key Lab Ocular Fundus Dis,Dept Op, Shanghai 200080, Peoples R China 2.Shanghai Novamab Biopharmaceut Co Ltd, Shanghai 201315, Peoples R China 3.Fudan Univ, Sch Pharm, Dept Pharmaceut,Natl Key Lab Adv Drug Formulat Ove, Minist Educ,Key Lab Smart Drug Delivery, Shanghai 201203, Peoples R China 4.Fudan Univ, Eye & ENT Hosp, Eye Inst, Shanghai 200031, Peoples R China 5.Fudan Univ, Eye & ENT Hosp, Dept Ophthalmol, Shanghai 200031, Peoples R China 6.Chinese Acad Sci, Shanghai Inst Mat Med, Ctr Drug Safety Evaluat & Res, State Key Lab Drug Res, Shanghai 201203, Peoples R China 7.Alephoson Biopharmaceut Ltd, Hong Kong, Peoples R China 8.Fudan Univ, Inst Integrat Med, Shanghai Engn Res Ctr ImmunoTherapeut, Shanghai 201203, Peoples R China 9.Quzhou Fudan Inst, Quzhou 324003, Peoples R China |
| 推荐引用方式 GB/T 7714 | Chen, Chong,Zhu, Min,Fan, Xingyan,et al. Continuous Suppression of Pathological Retinal and Choroidal Neovascularization in Cynomolgus Monkeys via Noninvasive Ophthalmic Delivery of a Novel Anti-VEGFA Nanobody and Proprietary Penetratin Analog Formulation[J]. ADVANCED SCIENCE,2025:13. |
| APA | Chen, Chong.,Zhu, Min.,Fan, Xingyan.,Lv, Kangjia.,Jiang, Kuan.,...&Xu, Xun.(2025).Continuous Suppression of Pathological Retinal and Choroidal Neovascularization in Cynomolgus Monkeys via Noninvasive Ophthalmic Delivery of a Novel Anti-VEGFA Nanobody and Proprietary Penetratin Analog Formulation.ADVANCED SCIENCE,13. |
| MLA | Chen, Chong,et al."Continuous Suppression of Pathological Retinal and Choroidal Neovascularization in Cynomolgus Monkeys via Noninvasive Ophthalmic Delivery of a Novel Anti-VEGFA Nanobody and Proprietary Penetratin Analog Formulation".ADVANCED SCIENCE (2025):13. |
入库方式： OAI收割
来源：上海药物研究所
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