Small Activating RNA
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Small Activating RNA
Small activating RNAs (saRNAs) are double-stranded RNA molecules that induce gene expression at the transcriptional level, a phenomenon known as RNA activation (RNAa). This contrasts with the gene silencing typically associated with small interfering RNAs (siRNAs) in RNA interference. saRNAs offer a novel approach to upregulate genes of therapeutic interest, and have progressed to clinical trials. Mechanism of Action saRNAs, typically 19 nucleotides in length with 2-nucleotide overhangs (similar to siRNAs), mediate RNAa through the RNA-induced transcriptional activation (RITA) complex. This complex includes Argonaute 2 (AGO2), RNA helicase A (RHA), and CTR9 (a component of the PAF1 complex). The RITA complex facilitates the transition of RNA polymerase II from a paused to an elongating state at the target gene's promoter, leading to increased transcription. (For a more detailed explanation of the mechanism, see RNA activation.) saRNA Design and Use Designing effect ...
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Self-amplifying RNA
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 MRNA vaccine#Amplification, vaccines and other therapeutic applications. As a "next-generation" mRNA, saRNA is designed to achieve greater protein expression with a reduced dose compared to conventional mRNA. Unlike conventional mRNA, which has a Messenger RNA#Degradation, short half-life and limited ability to express proteins for an extended time, saRNA can sustain protein expression for longer periods. saRNA are based on positive single stranded RNA viruses most commonly alphaviruses such as Venezuelan equine encephalitis virus. Conventional messenger RNA (mRNA) vaccines only produce a finite amount of protein due to the short mRNA half-life. saRNA extends the kinetics of expression by a second ORF encoding the protein machinery necessary f ...
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RNA Activation
RNA activation (RNAa) is a small RNA-guided and Argonaute (Ago)-dependent gene regulation phenomenon in which promoter-targeted short double-stranded RNAs (dsRNAs) induce target gene expression at the transcriptional/epigenetic level. RNAa was first reported in a 2006 PNAS paper by Li ''et al''. who also coined the term "RNAa" as a contrast to ''RNA interference ( RNAi)'' to describe such gene activation phenomenon. dsRNAs that trigger RNAa have been termed small activating RNA (saRNA).Li, Longcheng; Dahiya, Rajvir.Small Activating RNA Molecules and Methods of Use" U.S. Patent US 8,877,721 filed October 1, 2004, and issued November 4,2014. Unlike RNAi, where small RNAs typically lead to gene silencing, RNAa demonstrates that small RNAs can also act as activators of gene expression. History and Discovery The phenomenon of RNAa was first reported in 2006 by Long-Cheng Li and colleagues at University of California, San Francisco (UCSF). They demonstrated that synthetic dsRNAs, te ...
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RNA Interference
RNA interference (RNAi) is a biological process in which RNA molecules are involved in sequence-specific suppression of gene expression by double-stranded RNA, through translational or transcriptional repression. Historically, RNAi was known by other names, including ''co-suppression'', ''post-transcriptional gene silencing'' (PTGS), and ''quelling''. The detailed study of each of these seemingly different processes elucidated that the identity of these phenomena were all actually RNAi. Andrew Fire and Craig Mello shared the 2006 Nobel Prize in Physiology or Medicine for their work on RNAi in the nematode worm ''Caenorhabditis elegans'', which they published in 1998. Since the discovery of RNAi and its regulatory potentials, it has become evident that RNAi has immense potential in suppression of desired genes. RNAi is now known as precise, efficient, stable and better than antisense therapy for gene suppression. Antisense RNA produced intracellularly by an expression vector may be ...
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RNA Therapeutics
RNA therapeutics are a new class of medications based on RNA, ribonucleic acid (RNA). Research has been working on clinical use since the 1990s, with significant success in cancer therapy in the early 2010s. In 2020 and 2021, mRNA vaccines have been developed globally for use in combating the coronavirus disease 2019, coronavirus disease (COVID-19 pandemic). The Pfizer–BioNTech COVID-19 vaccine was the first mRNA vaccine approved by a Regulation of therapeutic goods, medicines regulator, followed by the Moderna COVID-19 vaccine, and others. The main types of RNA therapeutics are those based on messenger RNA (mRNA), antisense RNA (asRNA), RNA interference (RNAi), RNA activation (RNAa) and RNA aptamers. Of the four types, mRNA-based therapy is the only type which is based on triggering Protein biosynthesis, synthesis of proteins within cells, making it particularly useful in vaccine development. Antisense RNA is complementary to coding mRNA and is used to trigger mRNA inactivation ...
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