8JRE

Cryo-EM structure of a designed AAV8-based vector

これはPDB形式変換不可エントリーです。

8JRE の概要

• エントリーDOI: 10.2210/pdb8jre/pdb
• EMDBエントリー: 36594
• 分子名称: Capsid protein (1 entity in total)
• 機能のキーワード: aav8, virus
• 由来する生物種: Adeno-associated virus - 8
• タンパク質・核酸の鎖数: 60
• 化学式量合計: 3556211.46

構造登録者

Ke, X.,Luo, S.,Zheng, Q.,Jiang, H.,Liu, F.,Sun, X. (登録日: 2023-06-16, 公開日: 2024-04-24, 最終更新日: 2024-05-15)

主引用文献

Luo, S.,Jiang, H.,Li, Q.,Qin, Y.,Yang, S.,Li, J.,Xu, L.,Gou, Y.,Zhang, Y.,Liu, F.,Ke, X.,Zheng, Q.,Sun, X.
An adeno-associated virus variant enabling efficient ocular-directed gene delivery across species.
Nat Commun, 15:3780-3780, 2024

PubMed Abstract: Recombinant adeno-associated viruses (rAAVs) have emerged as promising gene therapy vectors due to their proven efficacy and safety in clinical applications. In non-human primates (NHPs), rAAVs are administered via suprachoroidal injection at a higher dose. However, high doses of rAAVs tend to increase additional safety risks. Here, we present a novel AAV capsid (AAVv128), which exhibits significantly enhanced transduction efficiency for photoreceptors and retinal pigment epithelial (RPE) cells, along with a broader distribution across the layers of retinal tissues in different animal models (mice, rabbits, and NHPs) following intraocular injection. Notably, the suprachoroidal delivery of AAVv128-anti-VEGF vector completely suppresses the Grade IV lesions in a laser-induced choroidal neovascularization (CNV) NHP model for neovascular age-related macular degeneration (nAMD). Furthermore, cryo-EM analysis at 2.1 Å resolution reveals that the critical residues of AAVv128 exhibit a more robust advantage in AAV binding, the nuclear uptake and endosome escaping. Collectively, our findings highlight the potential of AAVv128 as a next generation ocular gene therapy vector, particularly using the suprachoroidal delivery route.

PubMed: 38710714
DOI: 10.1038/s41467-024-48221-4

実験手法

ELECTRON MICROSCOPY (2.08 Å)