5OGI

Complex of a binding protein and human adenovirus C 5 hexon

Summary for 5OGI

• Entry DOI: 10.2210/pdb5ogi/pdb
• Descriptor: Hexon protein, scFv of 9C12 antibody, SULFATE ION, ... (7 entities in total)
• Functional Keywords: antibody, human adenovirus c5, gene therapy, viral protein
• Biological source: Mus musculus (House mouse); More
• Cellular location: Virion : P04133
• Total number of polymer chains: 2
• Total formula weight: 137695.20

Authors

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. (deposition date: 2017-07-13, release date: 2018-02-07, Last modification date: 2024-01-17)

Primary citation

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

Experimental method

X-RAY DIFFRACTION (2.8 Å)