Journal
ANALYTICAL AND BIOANALYTICAL CHEMISTRY
Volume 411, Issue 4, Pages 925-933Publisher
SPRINGER HEIDELBERG
DOI: 10.1007/s00216-018-1519-3
Keywords
Oncolytic virotherapy; T7 peptide; Self peptide; Copper-free click chemistry; Azide-enabled oncolytic vaccinia virus; Immunogenicity
Funding
- National Science and Technology Major Project [2018ZX 10301405-001]
- China Postdoctoral Science Foundation [2018M630076]
- National Natural Science Foundation of China [21874011]
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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.An engineered oncolytic vaccinia virus (OVV) was constructed by bioconjugating DBCO derivate T7 peptide and DBCO derivate self-peptide with azide-modified OVV via copper-free click chemistry. As a result, the tumor inhibit effect was significantly enhanced attributed to the prolonged in vivo circulation time and improved targeting recognition capability.
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