6NXE

Cryo-EM Reconstruction of Protease-Activateable Adeno-Associated Virus 9 (AAV9-L001)

これはPDB形式変換不可エントリーです。

6NXE の概要

• エントリーDOI: 10.2210/pdb6nxe/pdb
• EMDBエントリー: 0535
• 分子名称: Capsid protein VP1 (1 entity in total)
• 機能のキーワード: aav, activatable, gene therapy, provector, virus
• 由来する生物種: Adeno-associated virus
• タンパク質・核酸の鎖数: 60
• 化学式量合計: 3656350.08

構造登録者

Bennett, A.B.,Agbandje-Mckenna, M. (登録日: 2019-02-08, 公開日: 2019-03-13, 最終更新日: 2024-03-20)

主引用文献

Guenther, C.M.,Brun, M.J.,Bennett, A.D.,Ho, M.L.,Chen, W.,Zhu, B.,Lam, M.,Yamagami, M.,Kwon, S.,Bhattacharya, N.,Sousa, D.,Evans, A.C.,Voss, J.,Sevick-Muraca, E.M.,Agbandje-McKenna, M.,Suh, J.
Protease-Activatable Adeno-Associated Virus Vector for Gene Delivery to Damaged Heart Tissue.
Mol. Ther., 27:611-622, 2019

PubMed Abstract: Adeno-associated virus (AAV) has emerged as a promising gene delivery vector because of its non-pathogenicity, simple structure and genome, and low immunogenicity compared to other viruses. However, its adoption as a safe and effective delivery vector for certain diseases relies on altering its tropism to deliver transgenes to desired cell populations. To this end, we have developed a protease-activatable AAV vector, named provector, that responds to elevated extracellular protease activity commonly found in diseased tissue microenvironments. The AAV9-based provector is initially inactive, but then it can be switched on by matrix metalloproteinases (MMP)-2 and -9. Cryo-electron microscopy and image reconstruction reveal that the provector capsid is structurally similar to that of AAV9, with a flexible peptide insertion at the top of the 3-fold protrusions. In an in vivo model of myocardial infarction (MI), the provector is able to deliver transgenes site specifically to high-MMP-activity regions of the damaged heart, with concomitant decreased delivery to many off-target organs, including the liver. The AAV provector may be useful in the future for enhanced delivery of transgenes to sites of cardiac damage.

PubMed: 30772143
DOI: 10.1016/j.ymthe.2019.01.015

実験手法

ELECTRON MICROSCOPY (3.16 Å)