{"title":"迈向基于 SINEUP 的疗法：设计体外合成的 SINEUP RNA。","authors":"Paola Valentini, Bianca Pierattini, Elsa Zacco, Damiano Mangoni, Stefano Espinoza, Natalie A Webster, Byron Andrews, Piero Carninci, Gian Gaetano Tartaglia, Luca Pandolfini, Stefano Gustincich","doi":"10.1016/j.omtn.2022.01.021","DOIUrl":null,"url":null,"abstract":"<p><p>SINEUPs are a novel class of natural and synthetic non-coding antisense RNA molecules able to increase the translation of a target mRNA. They present a modular organization comprising an unstructured antisense target-specific domain, which sets the specificity of each individual SINEUP, and a structured effector domain, which is responsible for the translation enhancement. In order to design a fully functional <i>in vitro</i> transcribed SINEUP for therapeutics applications, SINEUP RNAs were synthesized <i>in vitro</i> with a variety of chemical modifications and screened for their activity on endogenous target mRNA upon transfection. Three combinations of modified ribonucleotides-2'O methyl-ATP (Am), N6 methyl-ATP (m6A), and pseudo-UTP (ψ)-conferred SINEUP activity to naked RNA. The best combination tested in this study was fully modified with m6A and ψ. Aside from functionality, this combination conferred improved stability upon transfection and higher thermal stability. Common structural determinants of activity were identified by circular dichroisms, defining a core functional structure that is achieved with different combinations of modifications.</p>","PeriodicalId":47687,"journal":{"name":"Disaster Prevention and Management","volume":"14 1","pages":"1092-1102"},"PeriodicalIF":1.9000,"publicationDate":"2022-02-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8857549/pdf/","citationCount":"0","resultStr":"{\"title\":\"Towards SINEUP-based therapeutics: Design of an <i>in vitro</i> synthesized SINEUP RNA.\",\"authors\":\"Paola Valentini, Bianca Pierattini, Elsa Zacco, Damiano Mangoni, Stefano Espinoza, Natalie A Webster, Byron Andrews, Piero Carninci, Gian Gaetano Tartaglia, Luca Pandolfini, Stefano Gustincich\",\"doi\":\"10.1016/j.omtn.2022.01.021\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>SINEUPs are a novel class of natural and synthetic non-coding antisense RNA molecules able to increase the translation of a target mRNA. They present a modular organization comprising an unstructured antisense target-specific domain, which sets the specificity of each individual SINEUP, and a structured effector domain, which is responsible for the translation enhancement. In order to design a fully functional <i>in vitro</i> transcribed SINEUP for therapeutics applications, SINEUP RNAs were synthesized <i>in vitro</i> with a variety of chemical modifications and screened for their activity on endogenous target mRNA upon transfection. Three combinations of modified ribonucleotides-2'O methyl-ATP (Am), N6 methyl-ATP (m6A), and pseudo-UTP (ψ)-conferred SINEUP activity to naked RNA. The best combination tested in this study was fully modified with m6A and ψ. Aside from functionality, this combination conferred improved stability upon transfection and higher thermal stability. Common structural determinants of activity were identified by circular dichroisms, defining a core functional structure that is achieved with different combinations of modifications.</p>\",\"PeriodicalId\":47687,\"journal\":{\"name\":\"Disaster Prevention and Management\",\"volume\":\"14 1\",\"pages\":\"1092-1102\"},\"PeriodicalIF\":1.9000,\"publicationDate\":\"2022-02-02\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8857549/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Disaster Prevention and Management\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1016/j.omtn.2022.01.021\",\"RegionNum\":4,\"RegionCategory\":\"环境科学与生态学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2022/3/8 0:00:00\",\"PubModel\":\"eCollection\",\"JCR\":\"Q3\",\"JCRName\":\"ENVIRONMENTAL STUDIES\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Disaster Prevention and Management","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1016/j.omtn.2022.01.021","RegionNum":4,"RegionCategory":"环境科学与生态学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2022/3/8 0:00:00","PubModel":"eCollection","JCR":"Q3","JCRName":"ENVIRONMENTAL STUDIES","Score":null,"Total":0}
Towards SINEUP-based therapeutics: Design of an in vitro synthesized SINEUP RNA.
SINEUPs are a novel class of natural and synthetic non-coding antisense RNA molecules able to increase the translation of a target mRNA. They present a modular organization comprising an unstructured antisense target-specific domain, which sets the specificity of each individual SINEUP, and a structured effector domain, which is responsible for the translation enhancement. In order to design a fully functional in vitro transcribed SINEUP for therapeutics applications, SINEUP RNAs were synthesized in vitro with a variety of chemical modifications and screened for their activity on endogenous target mRNA upon transfection. Three combinations of modified ribonucleotides-2'O methyl-ATP (Am), N6 methyl-ATP (m6A), and pseudo-UTP (ψ)-conferred SINEUP activity to naked RNA. The best combination tested in this study was fully modified with m6A and ψ. Aside from functionality, this combination conferred improved stability upon transfection and higher thermal stability. Common structural determinants of activity were identified by circular dichroisms, defining a core functional structure that is achieved with different combinations of modifications.
期刊介绍：
Disaster Prevention and Management, An International Journal, sets out to advance the available knowledge in the fields of disaster prevention and management and to act as an integrative agent for extant methodologies and activities relating to disaster emergency and crisis management. Publishing high quality, refereed papers, the journal supports the exchange of ideas, experience and practice between academics, practitioners and policy-makers.
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