Self-amplifying mRNAs derived from the genomes of positive-strand RNA viruses have recently come into focus as a promising technology platform for vaccine development. Non-virally delivered self-amplifying mRNA vaccines have the potential to be highly versatile, potent, streamlined, scalable, and inexpensive. By amplifying their genome and the antigen encoding mRNA in the host cell, the self-amplifying mRNA mimics a viral infection, resulting in sustained levels of the target protein combined with self-adjuvanting innate immune responses, ultimately leading to potent and long-lasting antigen-specific humoral and cellular immune responses. Moreover, in principle, any eukaryotic sequence could be encoded by self-amplifying mRNA without the need to change the manufacturing process, thereby enabling a much faster and flexible research and development timeline than the current vaccines and hence a quicker response to emerging infectious diseases. This chapter highlights the rapid progress made in using non-virally delivered self-amplifying mRNA-based vaccines against infectious diseases in animal models. We provide an overview of the unique attributes of this vaccine approach, summarize the growing body of work defining its mechanism of action, discuss the current challenges and latest advances, and highlight perspectives about the future of this promising technology.
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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 PDFAlphaviral backbone of self-amplifying RNA enhances protein expression and immunogenicity against SARS-CoV-2 antigen.
Mol Ther
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Michael Smith Laboratories, University of British Columbia, Vancouver V6T1Z4, BC, Canada; School of Biomedical Engineering, University of British Columbia, Vancouver V6T1Z4, BC, Canada. 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 with 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.
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Res Pharm Sci
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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.
Self-amplifying mRNA vaccines protect elderly BALB/c mice against a lethal respiratory syncytial virus infection.
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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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