Year: 2022
Type: article
Abstract: Circular RNAs (circRNAs) are stable and prevalent RNAs in eukaryotic cells that arise from back-splicing. Synthetic circRNAs and some endogenous circRNAs can encode proteins, raising the promise of circRNA as a platform for gene expression. In this study, we developed a systematic approach for rapid assembly and testing of features that affect protein production from synthetic circRNAs. To maximize circRNA translation, we optimized five elements: vector topology, 5' and 3' untranslated regions, internal ribosome entry sites and synthetic aptamers recruiting translation initiation machinery. Together, these design principles improve circRNA protein yields by several hundred-fold, provide increased translation over messenger RNA in vitro, provide more durable translation in vivo and are generalizable across multiple transgenes.
Source: Nature Biotechnology
Language: English
Topic: Circular RNAs in diseases
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: hybrid
Estimated APC paid: $11,390
Funders: National Science Foundation, Howard Hughes Medical Institute, National Institutes of Health, National Human Genome Research Institute, National Eye Institute, National Cancer Institute, National Institute of General Medical Sciences, National Institute of Arthritis and Musculoskeletal and Skin Diseases, Division of Chemistry
Awards: G2911450482, Synthetic Studies Related to Cancer Research/Treatment, Graduate Training Program in Biotechnology, G4681491570, Graduate Research Fellowship Program (GRFP), G5520316217, Functional Materials Through Synthesis Informed Design, G6661425536, LncRNA mechanisms in cancer, G9000014149, Systematic identification of RNA sequences and protein components regulating circular RNA translation, Synthetic Studies Related to Cancer Research/Treatment, Stanford Vision Training Program, Training Program in Adult and Pediatric Rheumatology
OpenAlex ID: W4285728587