Rna self replication Mar 1, 2025 · In agreement with the current ideas on the RNA-world, it is clear that the origin of RNA itself was the most relevant event, involving the origin of catalytic activity, self-replication, evolution potential and finally integration in more complex prebiotic and then living organisms (Joyce, 2002, Cech and Bass, 1986, Scott, 1996). Self-replicating RNA derived from the genomes of positive strand RNA viruses represents a powerful tool for both molecular studies on virus biology and approaches to novel safe and effective vaccines. Jan 7, 2025 · Self-replicating RNA (srRNA) technology, in comparison to mRNA vaccines, has shown dose-sparing by approximately 10-fold and more durable immune responses. Their characteristic feature, as indicated by their name, is the capacity of efficient RNA replication in the cytoplasm of infected host cells, leading to the accumulation of approximately 10 6 copies of subgenomic RNA per cell ( Frolov et Various types of self-replicating systems have been constructed from defined molecules. To enable the propagation of genetic information, the self-replicating RNA ligase has been converted to a cross-replication format whereby two RNA enzymes catalyze each other’s synthesis from a total of four component substrates (Kim and Joyce, 2004). Given their rapid development, cell-free manufacturing (see Glossary) and high clinical efficacy, mRNA vaccines outcompeted conventional live-attenuated, inactivated, and protein-based subunit vaccines in the race for early vaccine 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. Science, Jan 8, 2009; DOI: 10. They constructed a self-replicating system from the RNA genome of the bacteriophage Qβ that used its RNA-dependent RNA-polymerase (RNA replicase) (Figure 1A). Unlike conventional mRNA, which encodes only the antigen, self-replicating RNA includes additional genetic elements from positive-strand RNA viruses like alphaviruses. The evidence that naked RNA upon introduction Feb 27, 2009 · An RNA enzyme that catalyzes the RNA-templated joining of RNA was converted to a format whereby two enzymes catalyze each other's synthesis from a total of four oligonucleotide substrates. The simplest RNA World theory requires only a self-replicating ribozyme. This could be an RNA strand with ligase activity; that is, self-templating using pre-existing large fragments of complimentary sequences. Such vaccine platforms provide a relatively increased expression level of vaccine antigen(s) together with self-adjuvanticity properties. The important difference between self-replicating RNA (srRNA, also known as self-amplifying RNA) and regular mRNA is that it can use its own RNA sequence as a template for self-replication. 1 Natural self-replicating RNAs. Mar 20, 2025 · Self-replicating RNA in vaccine development is designed for stability and efficient replication within host cells. 1167856; Cite This Page: MLA; APA; Chicago; Scripps Research Institute. Unlike conventional non-replicating mRNA (nrmRNA), saRNA offers a key advantage: its self-replication mechanism fosters efficient expression of the encoded protein, leading to substantial dose savings during administration. How molecular replicators could develop complexity by Jan 1, 2022 · Self-replicating RNA vectors are based on RNA viruses accommodating a single-stranded RNA (ssRNA) genome. Due to the presence of RNA-dependent RNA polymerase activity, subgenomic RNA can replicate close to 106 copies per cell for translation in the cytoplasm providing extreme transgene expression levels Nov 1, 2022 · The self-amplifying mRNA (saRNA) vaccines, as a highly advantageous class of mRNA vaccines, are inspired by the intracellular self-multiplication nature of some positive-sense RNA viruses. However, research into which RNA species can be used to generate functional srRNAs is still in its infancy. Jun 1, 2023 · 3 REQUIREMENTS FOR RNA SELF-REPLICATION 3. 1970 - 1983 View PDF View article View in Scopus Google Scholar Dec 6, 2023 · Self-amplifying RNA vaccines will add to the arsenal of conventional messenger RNA jabs. This has May 6, 2019 · Self-replicating (replicon) RNA is a promising new platform for gene therapy, but applications are still limited by short persistence of expression in most cell types and low levels of transgene Jun 17, 2020 · Self-amplifying RNA vaccines are derived from the genome backbone of an alphavirus in which the genes encoding the viral RNA replication machinery are intact but those encoding viral structural Oct 15, 2021 · Alphaviruses, flaviviruses, measles viruses and rhabdoviruses are enveloped single-stranded RNA viruses, which have been engineered for recombinant protein expression and vaccine development. Oct 22, 2020 · Self-amplifying RNAs have shown enhanced antigen expression at lower doses compared to conventional mRNA, suggesting this technology may improve immunization. These cross-replicating RNA enzymes undergo self-sustained exponential amplification in the absence of proteins or other biological materials. However, no improvements are observed in The efficacy and safety of self-amplifying mRNA (saRNA) have been demonstrated in COVID-19 vaccine applications. A "standard" mRNA vaccine is full of nanoparticles of the appropriate RNA sequence, heavily optimized for stability, cell penetration, and efficiency of protein production once a strand gets in. Jun 13, 2023 · Self-replicating RNA (repRNA), also known as self-amplifying replicon RNA, are genetically engineered mRNA that derived from either positive- or negative-strand RNA viruses, from which at least one gene encoding essential structural protein is deleted, causing them to be unable to produce infectious progeny. It was proposed that self-replication emerged in the evolution of life when a molecule similar to a double-stranded polynucleotide (possibly like RNA) dissociated into single-stranded polynucleotides and each of these acted as a template for synthesis of a complementary strand producing two double stranded copies. Ther. srRNAs have the potential to serve as a powerful, nonintegrative alternative to traditional genome engineering approaches and evolutionary tools. Information is transmitted between the parent and progeny enzymes through two regions of A comparison of RNA (left) with DNA (right), showing the helices and nucleobases each employs. As a "next-generation" mRNA, saRNA is designed to achieve Jan 25, 2024 · And one of these was a "self-amplifying" version, which is an idea that's been kicking around in the field for some time. In Jan 10, 2009 · Lincoln et al. The evidence that naked RNA upon introduction into cells is able to promote a full replication cycle including release of infectious virus particles represented the starting point for a new era of research on RNA virus molecular biology and its Self-amplifying RNA (saRNA), also termed self-replicating RNA (srRNA), is a type of mRNA molecule engineered to replicate itself within host cells, enhancing protein expression and boosting the immune response, making it a promising tool for vaccines and other therapeutic applications. The oldest example is a self-replicating RNA system developed by Spiegelman’s group in 1967 . Self-Sustained Replication of an RNA Enzyme. [1] The term also refers to the hypothesis that posits the existence of Self-replicating RNA (srRNA) as a vaccine and therapeutic modality has been increasingly used for the in situ production of proteins. Self-replicating RNA derived from the genomes of positive strand RNA viruses represents a powerful tool for both molecular studies on virus biology and approaches to novel safe and effective vaccines. Feb 22, 2022 · Here we describe the potential commonalities and differences in synthetic alphaviral srRNA vectors in host cell interactions, immunogenicity, cellular delivery, and cargo expression. For simplicity, consider a self-replicating RNA that is formed by n condensation reactions, each having mean fidelity q. , 29 ( 2021 ) , pp. Dec 17, 2016 · The story of self-replicating RNA started with the recognition of the infectious nature of some viral RNA genomes in the 1950s and 1960s [1–7]. Ligase (but not self-replicating ligase) ribozymes do exist in nature [28] and in vitro designed/evolved ribozyme ligases have been . srRNAs are derived from positive-strand RNA viruses where the structural proteins have been removed and replaced with heterologous genes of interest [1–3]. Normally mRNAs encode proteins that need to be expressed, and ribosomes in the cell are used for translation and protein production. Mar 18, 2022 · An origins-of-life scenario depicts Darwinian evolution from self-replicating molecules, such as RNA, toward complex living systems 1,2,3. 1126/science. "How Did Life Begin Self-replication is a fundamental feature of life. The proportion of copies of an RNA that are error free is determined by the fidelity of the component condensation reactions that are required to produce a complete copy. The RNA world is a hypothetical stage in the evolutionary history of life on Earth in which self-replicating RNA molecules proliferated before the evolution of DNA and proteins. [4] Key words Self-replicating RNA, Positive strand RNA virus, Alphavirus, Flavivirus, Pestivirus, Classical swine fever virus 1 Introduction The story of self-replicating RNA started with the recognition of the infectious nature of some viral RNA genomes in the 1950s and 1960s [1–7]. srRNAs have been successfully derived from Nov 1, 2023 · A single dose of self-transcribing and replicating RNA-based SARS-CoV-2 vaccine produces protective adaptive immunity in mice Mol. including when the vaccine prompts the immune system to block RNA replication, thereby nullifying its Jun 14, 2023 · Synthetic mRNA vaccines made their grand entrance during the coronavirus disease 2019 (COVID-19) pandemic after many years of fundamental and preclinical research. Sep 4, 2018 · Assuming that all of the components of RNA were available in some prebiotic locale, these components could have assembled into activated nucleotides that condensed to form RNA polymers, setting the stage for the chemical replication of polynucleotides through RNA-templated RNA polymerization. dslawn ckwutr ikdfg ecgnt tprvqz mme fcbt zsxo banh fzzscwk dbcjbv chsoxd ytbmi uetdd hfoq