Duncan NRI Faculty and Staff Publications
Language
English
Publication Date
10-26-2023
Journal
Nature Communications
DOI
10.1038/s41467-023-42252-z
PMID
37884512
PMCID
PMC10603104
PubMedCentral® Posted Date
10-26-2023
PubMedCentral® Full Text Version
Post-print
Abstract
Technologies capable of programmable translation activation offer strategies to develop therapeutics for diseases caused by insufficient gene expression. Here, we present "translation-activating RNAs" (taRNAs), a bifunctional RNA-based molecular technology that binds to a specific mRNA of interest and directly upregulates its translation. taRNAs are constructed from a variety of viral or mammalian RNA internal ribosome entry sites (IRESs) and upregulate translation for a suite of target mRNAs. We minimize the taRNA scaffold to 94 nucleotides, identify two translation initiation factor proteins responsible for taRNA activity, and validate the technology by amplifying SYNGAP1 expression, a haploinsufficiency disease target, in patient-derived cells. Finally, taRNAs are suitable for delivery as RNA molecules by lipid nanoparticles (LNPs) to cell lines, primary neurons, and mouse liver in vivo. taRNAs provide a general and compact nucleic acid-based technology to upregulate protein production from endogenous mRNAs, and may open up possibilities for therapeutic RNA research.
Keywords
Animals, Mice, Humans, Protein Biosynthesis, Up-Regulation, Gene Expression Regulation, RNA, Messenger, Internal Ribosome Entry Sites, Mammals, Synthetic biology, RNA, Translation, Ribosome, Gene regulation
Published Open-Access
yes
Recommended Citation
Cao, Yang; Liu, Huachun; Lu, Shannon S; et al., "RNA-Based Translation Activators for Targeted Gene Upregulation" (2023). Duncan NRI Faculty and Staff Publications. 71.
https://digitalcommons.library.tmc.edu/duncar_nri_pub/71
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Genetic Phenomena Commons, Medical Genetics Commons, Neurology Commons, Neurosciences Commons