Hepatitis B virus neutralization with DNA origami nanoshells

We demonstrate the use of DNA origami to create virus-trapping nanoshells that efficiently neutralize hepatitis B virus (HBV) in cell culture. By modifying the shells with a synthetic monoclonal antibody that binds to the HBV envelope, the effective neutralization potency per antibody is increased b...

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Bibliographic Details
Published in:bioRxiv 2023-12
Main Authors: Elena-Marie Willner, Kolbe, Fenna, Momburg, Frank, Protzer, Ulrike, Dietz, Hendrik
Format: Article
Language:English
Subjects:
Antiviral agents
Avidity
Cell culture
Deoxyribonucleic acid
DNA
DNA viruses
Hepatitis B
Monoclonal antibodies
Shells
Trapping
Virions
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Summary:We demonstrate the use of DNA origami to create virus-trapping nanoshells that efficiently neutralize hepatitis B virus (HBV) in cell culture. By modifying the shells with a synthetic monoclonal antibody that binds to the HBV envelope, the effective neutralization potency per antibody is increased by approximately 100 times compared to using free antibodies. The improvements in neutralizing the virus are attributed to two factors: first, the shells act as a physical barrier that block the virus from interacting with host cells; second, the multivalent binding of the antibodies inside the shells lead to stronger attachment to the trapped virus, a phenomenon known as avidity. Pre-incubation of shells with HBV and simultaneous addition of both components separately to cells lead to comparable levels of neutralization, indicating rapid trapping of the virions by the shells. Our study highlights the potential of the DNA shell system to rationally create novel antivirals using components that, when used individually, show little to no antiviral effectiveness.Competing Interest StatementThe authors have declared no competing interest.
DOI:10.1101/2023.12.20.572526