Introduction: Self-amplifying mRNA vaccines are being developed as a platform technology with potential to be used for a broad range of targets. The synthetic production methods for their manufacture, combined with the modern tools of bioinformatics and synthetic biology, enable these vaccines to be produced rapidly from an electronic gene sequence. Preclinical proof of concept has so far been achieved for influenza, respiratory syncytial virus, rabies, Ebola, cytomegalovirus, human immunodeficiency virus and malaria.
Areas Covered: This editorial highlights the key milestones in the discovery and development of self-amplifying mRNA vaccines, and reviews how they might be used as a rapid response platform. The paper points out how future improvements in RNA vector design and non-viral delivery may lead to decreases in effective dose and increases in production capacity.
Expert Opinion: The prospects for non-viral delivery of self-amplifying mRNA vaccines are very promising. Like other types of nucleic acid vaccines, these vaccines have the potential to draw on the positive attributes of live-attenuated vaccines while obviating many potential safety limitations. Hence, this approach could enable the concept of vaccines on demand as a rapid response to a real threat rather than the deployment of strategic stockpiles based on epidemiological predictions for possible threats.
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http://dx.doi.org/10.1517/17460441.2015.996128 | DOI Listing |
Mol Ther Nucleic Acids
March 2025
Department of Infectious Disease, Imperial College London, London W2 1PG, UK.
Self-amplifying RNA (saRNA) is an extremely promising platform because it can produce more protein for less RNA. We used a sort and sequence approach to identify host cell factors associated with transgene expression from saRNA; the hypothesis was that cells with different expression levels would have different transcriptomes. We tested this in CDK4/hTERT immortalized human muscle cells transfected with Venezuelan equine encephalitis virus (VEEV)-derived saRNA encoding GFP.
View Article and Find Full Text PDFMol Ther
December 2024
Michael Smith Laboratories, University of British Columbia, Vancouver, Canada V6T1Z4; School of Biomedical Engineering, University of British Columbia, Vancouver, Canada V6T1Z4. Electronic address:
Self-amplifying RNA (saRNA) vectors are a next-generation RNA technology that extends the expression of heterologous genes. Clinical trials have shown the dose-sparing capacity of saRNA vectors in a vaccine context compared to conventional messenger RNA. However, saRNA vectors have historically been based on a limited number of alphaviruses, and only the Venezuelan equine encephalitis virus-based saRNA vaccines have been used clinically.
View Article and Find Full Text PDFIntroduction: Dozens of vaccines have been approved or authorized internationally in response to the ongoing SARS-CoV-2 pandemic, covering a range of modalities and routes of delivery. For example, mucosal delivery of vaccines via the intranasal (i.n.
View Article and Find Full Text PDFRes Pharm Sci
October 2024
School of Life Sciences and Technology, Institut Teknologi Bandung, Jalan Ganesa 10, Bandung 40132, Indonesia.
Background And Purpose: Massive vaccine distribution is a crucial step to prevent the spread of SARS-CoV2 as the causative agent of COVID-19. This research aimed to design the multi-epitope self-amplifying mRNA (saRNA) vaccine from the spike and nucleocapsid proteins of SARS-CoV2.
Experimental Approach: Commonly distributed constructions class I and II alleles of the Indonesian population were used to determine peptide sequences that trigger this population's high specificity T-cell response.
Mol Ther
December 2024
Viral Hemorrhagic Fevers Research Unit, Institut Pasteur of Shanghai (now Shanghai Institute of Immunity and Infection), Chinese Academy of Sciences, Shanghai 201203, China; Virology Laboratory, Institut Pasteur du Laos, Vientiane 01030, Laos. Electronic address:
Respiratory syncytial virus (RSV) represents a significant threat, being a primary cause of critical lower respiratory tract infections and fatalities among infants and the elderly worldwide, and poses a challenge to global public health. This urgent public health challenge necessitates the swift development of safe and effective vaccines capable of eliciting robust immune responses at low doses. Addressing this need, our study investigated five self-amplifying mRNA (sa-mRNA) candidate vaccines that encode the various pre-fusion conformations of the RSV fusion protein.
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