6EQC

Cryo-EM reconstruction of a complex of a binding protein and human adenovirus C5 hexon

6EQC の概要

• エントリーDOI: 10.2210/pdb6eqc/pdb
• 関連するPDBエントリー: 5OGI
• EMDBエントリー: 3821
• 分子名称: Hexon protein, scFv of 9C12 antibody (2 entities in total)
• 機能のキーワード: antibody, human adenovirus c5, gene therapy viral protein, viral protein
• 由来する生物種: Mus musculus (House Mouse); 詳細
• 細胞内の位置: Virion : P04133
• タンパク質・核酸の鎖数: 6
• 化学式量合計: 405896.08

構造登録者

Schmid, M.,Ernst, P.,Honegger, A.,Suomalainen, M.,Zimmermann, M.,Braun, L.,Stauffer, S.,Thom, C.,Dreier, B.,Eibauer, M.,Kipar, A.,Vogel, V.,Greber, U.F.,Medalia, O.,Plueckthun, A. (登録日: 2017-10-12, 公開日: 2018-02-07, 最終更新日: 2024-11-13)

主引用文献

Schmid, M.,Ernst, P.,Honegger, A.,Suomalainen, M.,Zimmermann, M.,Braun, L.,Stauffer, S.,Thom, C.,Dreier, B.,Eibauer, M.,Kipar, A.,Vogel, V.,Greber, U.F.,Medalia, O.,Pluckthun, A.
Adenoviral vector with shield and adapter increases tumor specificity and escapes liver and immune control.
Nat Commun, 9:450-450, 2018

PubMed Abstract: Most systemic viral gene therapies have been limited by sequestration and degradation of virions, innate and adaptive immunity, and silencing of therapeutic genes within the target cells. Here we engineer a high-affinity protein coat, shielding the most commonly used vector in clinical gene therapy, human adenovirus type 5. Using electron microscopy and crystallography we demonstrate a massive coverage of the virion surface through the hexon-shielding scFv fragment, trimerized to exploit the hexon symmetry and gain avidity. The shield reduces virion clearance in the liver. When the shielded particles are equipped with adaptor proteins, the virions deliver their payload genes into human cancer cells expressing HER2 or EGFR. The combination of shield and adapter also increases viral gene delivery to xenografted tumors in vivo, reduces liver off-targeting and immune neutralization. Our study highlights the power of protein engineering for viral vectors overcoming the challenges of local and systemic viral gene therapies.

PubMed: 29386504
DOI: 10.1038/s41467-017-02707-6

実験手法

ELECTRON MICROSCOPY (7.4 Å)