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Open AccessFeature PaperReview

Self-Replicating RNA Viruses for RNA Therapeutics

PanTherapeutics, Route de Lavaux 49, CH1095 Lutry, Switzerland
Molecules 2018, 23(12), 3310; https://doi.org/10.3390/molecules23123310
Received: 16 November 2018 / Revised: 10 December 2018 / Accepted: 11 December 2018 / Published: 13 December 2018
(This article belongs to the Special Issue Therapeutic Nucleic Acids: Past, Present, and Future)
Self-replicating single-stranded RNA viruses such as alphaviruses, flaviviruses, measles viruses, and rhabdoviruses provide efficient delivery and high-level expression of therapeutic genes due to their high capacity of RNA replication. This has contributed to novel approaches for therapeutic applications including vaccine development and gene therapy-based immunotherapy. Numerous studies in animal tumor models have demonstrated that self-replicating RNA viral vectors can generate antibody responses against infectious agents and tumor cells. Moreover, protection against challenges with pathogenic Ebola virus was obtained in primates immunized with alphaviruses and flaviviruses. Similarly, vaccinated animals have been demonstrated to withstand challenges with lethal doses of tumor cells. Furthermore, clinical trials have been conducted for several indications with self-amplifying RNA viruses. In this context, alphaviruses have been subjected to phase I clinical trials for a cytomegalovirus vaccine generating neutralizing antibodies in healthy volunteers, and for antigen delivery to dendritic cells providing clinically relevant antibody responses in cancer patients, respectively. Likewise, rhabdovirus particles have been subjected to phase I/II clinical trials showing good safety and immunogenicity against Ebola virus. Rhabdoviruses have generated promising results in phase III trials against Ebola virus. The purpose of this review is to summarize the achievements of using self-replicating RNA viruses for RNA therapy based on preclinical animal studies and clinical trials in humans. View Full-Text
Keywords: self-amplifying RNA virus; vaccine; cancer therapy; immunotherapy; neutralizing antibodies; protection against viral and tumor challenges; clinical trials self-amplifying RNA virus; vaccine; cancer therapy; immunotherapy; neutralizing antibodies; protection against viral and tumor challenges; clinical trials
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Lundstrom, K. Self-Replicating RNA Viruses for RNA Therapeutics. Molecules 2018, 23, 3310.

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