Engineering oncolytic vaccinia virus with functional peptides through mild and universal strategy
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Oncolytic virotherapy is one of promising tumor therapy modalities. However, its therapeutic efficacy is still limited due to the immunogenicity and poor tumor-targeting capability. In this report, an engineered oncolytic vaccinia virus (OVV) was constructed by site-specifically introducing azide groups to the envelope of OVV during the in situ assembling process of virions. Subsequently, dibenzocyclooctynes (DBCO) derivate T7 peptide and DBCO derivate self-peptide were simultaneously conjugated to the azide-modified OVV (azide-OVV) via copper-free click chemistry. The infectivity of peptide-conjugated virus was well kept. Meanwhile, both of the targeting capacity to transferrin receptor (TfR)-overexpressed tumor cells and the in vivo blood circulation time increased. Therefore, the growth of TfR-positive tumor could be significantly inhibited after intravenously injecting the engineered OVV, while no noticeable side effects. This construction strategy can be popularized to other enveloped oncolytic virus (OV), thus a universal engineering platform can be provided for OV cancer therapy.
KeywordsOncolytic virotherapy T7 peptide Self peptide Copper-free click chemistry Azide-enabled oncolytic vaccinia virus Immunogenicity
We thank Xin-Yuan Liu for providing oncolytic vaccinia virus (OncoPox-IL24-MnSOD). We thank Wei Wei of Institute of Process Engineering, Chinese Academy of Sciences, for his help in animal experiments.
This work was supported by the National Science and Technology Major Project (No. 2018ZX 10301405-001), China Postdoctoral Science Foundation (No. 2018M630076), and National Natural Science Foundation of China (No. 21874011).
Compliance with ethical standards
The authors declare that they have no competing interest.
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