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Review
. 2023 Jun;30(6):771-784.
doi: 10.1038/s41417-022-00436-7. Epub 2022 Feb 15.

Self-replicating vehicles based on negative strand RNA viruses

Kenneth Lundstrom  1
Affiliations
Review

Self-replicating vehicles based on negative strand RNA viruses

Kenneth Lundstrom. Cancer Gene Ther. 2023 Jun.

Abstract

Self-replicating RNA viruses have been engineered as efficient expression vectors for vaccine development for infectious diseases and cancers. Moreover, self-replicating RNA viral vectors, particularly oncolytic viruses, have been applied for cancer therapy and immunotherapy. Among negative strand RNA viruses, measles viruses and rhabdoviruses have been frequently applied for vaccine development against viruses such as Chikungunya virus, Lassa virus, Ebola virus, influenza virus, HIV, Zika virus, and coronaviruses. Immunization of rodents and primates has elicited strong neutralizing antibody responses and provided protection against lethal challenges with pathogenic viruses. Several clinical trials have been conducted. Ervebo, a vaccine based on a vesicular stomatitis virus (VSV) vector has been approved for immunization of humans against Ebola virus. Different types of cancers such as brain, breast, cervical, lung, leukemia/lymphoma, ovarian, prostate, pancreatic, and melanoma, have been the targets for cancer vaccine development, cancer gene therapy, and cancer immunotherapy. Administration of measles virus and VSV vectors have demonstrated immune responses, tumor regression, and tumor eradication in various animal models. A limited number of clinical trials have shown well-tolerated treatment, good safety profiles, and dose-dependent activity in cancer patients.

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Conflict of interest statement

The author declares no competing interests.

Figures

Fig. 1
Fig. 1. Expression vectors for self-replicating negative strand RNA viruses.
A Measles virus: the gene of interest is introduced either between the P and M genes or the H and L genes (maximum packaging capacity of 6 kb). B Vesicular stomatitis virus: for pseudotyped VSV the VSV-G gene is replaced by the foreign gene. Alternatively, foreign genes are introduced between the M and G genes and/or the G and L genes (maximum packaging capacity of 6 kb). C Rabies virus: the gene of interest is introduced between the N and P genes or between the G and L genes (maximum packaging capacity of 6 kb). CMV cytomegalovirus promoter; Fu fusion protein, G glycoprotein; Gol gene of interest; H hemagglutinin; L large protein; M matrix protein; N nucleocapsid; P phosphoprotein; T7 T7 RNA polymerase promoter; T7T T7 terminal sequence.
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