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Polymorphic nanobody crystals as long-acting intravitreal therapy for wet age-related macular degeneration.

ABSTRACT: Wet age-related macular degeneration (wet AMD) is the most common cause of blindness, and chronic intravitreal injection of anti-vascular endothelial growth factor (VEGF) proteins has been the dominant therapeutic approach. Less intravitreal injection and a prolonged inter-injection interval are the main drivers behind new wet AMD drug innovations. By rationally engineering the surface residues of a model anti-VEGF nanobody, we obtained a series of anti-VEGF nanobodies with identical protein structures and VEGF binding affinities, while drastically different crystallization propensities and crystal lattice structures. Among these nanobody crystals, the P2₁2₁2₁ lattice appeared to be denser and released protein slower than the P1 lattice, while nanobody crystals embedding zinc coordination further slowed the protein release rate. The polymorphic protein crystals could be a potentially breakthrough strategy for chronic intravitreal administration of anti-VEGF proteins.

SUBMITTER: Zhu S

PROVIDER: S-EPMC10658565 | biostudies-literature | 2023 Nov

REPOSITORIES: biostudies-literature

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Polymorphic nanobody crystals as long-acting intravitreal therapy for wet age-related macular degeneration.

Zhu Shuqian S Fan Shilong S Tang Tianxin T Huang Jinliang J Zhou Heng H Huang Chengnan C Chen Youxin Y Qian Feng F

Bioengineering & translational medicine 20230504 6

Wet age-related macular degeneration (wet AMD) is the most common cause of blindness, and chronic intravitreal injection of anti-vascular endothelial growth factor (VEGF) proteins has been the dominant therapeutic approach. Less intravitreal injection and a prolonged inter-injection interval are the main drivers behind new wet AMD drug innovations. By rationally engineering the surface residues of a model anti-VEGF nanobody, we obtained a series of anti-VEGF nanobodies with identical protein str ...[more]

PMID: 38023710

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Project description:BackgroundSeveral studies have investigated the efficacy and safety of Conbercept versus Triamcinolone acetonide for the treatment of wet age-related macular degeneration (wAMD), but the results are controversial. Therefore, this meta-analysis aims to evaluate the efficacy and safety of Conbercept versus Triamcinolone acetonide for the treatment of wAMD.MethodsA total of seven databases were searched for literature on the treatment of wAMD with Conbercept, with the search period from database inception to May 2024. Patients in the experimental group received Conbercept treatment, while patients in the control group received Triamcinolone acetonide treatment. The observed indicators included central macular thickness, incidence of adverse reactions, clinical efficacy, and best-corrected visual acuity. Relative risk (RR) and mean difference (MD) were used as effect measures.ResultsA total of 12 studies with 864 patients were included in the meta-analysis. The results showed that the experimental group had a significantly better central macular thickness (MD = - 42.68, 95% CI = - 55.04 ~ - 30.32, P < 0.001), clinical response rate (RR = 1.25, 95% CI = 1.12 ~ 1.39, P < 0.001), and best-corrected visual acuity (MD = 0.16, 95% CI = 0.12 ~ 0.20, P < 0.001) compared to the control group. In terms of adverse events, the overall incidence of adverse events was lower in the experimental group (RR = 0.26, 95% CI = 0.14 ~ 0.51, P < 0.001) compared to the control group. Specifically, the incidence of intraocular pressure elevation (RR = 0.33, 95% CI = 0.12 ~ 0.94, P = 0.04) and intraocular inflammation (RR = 0.17, 95% CI = 0.03 ~ 0.97, P = 0.05) was lower in the experimental group compared to the control group, but there was no significant difference in the incidence of subconjunctival hemorrhage (RR = 0.7, 95% CI = 0.14 ~ 3.5, P = 0.66) and corneal edema (RR = 0.2, 95% CI = 0.04 ~ 1.12, P = 0.07).ConclusionConbercept demonstrated superior efficacy in treating wAMD compared to triamcinolone acetonide, with a lower incidence of adverse reactions. However, the current meta-analysis included a limited number of studies, with only two studies evaluating best-corrected visual acuity (BCVA). Further high-quality randomized controlled trials (RCTs) are warranted to validate these findings.

Dataset Information

Polymorphic nanobody crystals as long-acting intravitreal therapy for wet age-related macular degeneration.

Publications

Polymorphic nanobody crystals as long-acting intravitreal therapy for wet age-related macular degeneration.

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