Cyclic RNA switches that regulate gene expression in a cell type-specific manner

Credit: Nucleic Acids Research (2023). DOI: 10.1093/nar/gkac1252

The Hirohide Saito Laboratory has developed cyclic RNA switches that can control gene expression in a cell type-specific manner using miRNAs and RNA-binding proteins and has successfully constructed an artificial gene circuit by combining them. Gene transfer technology using synthetic mRNA has the advantages of low risk of genome damage and high transfer efficiency compared to DNA, and thus has a wide range of potential applications, including vaccines, gene therapy, and genome editing. However, RNA is unstable in the cell, making it difficult to sustain gene expression, which is an application challenge.

Because they are not easily degraded in the cells, cyclic RNAs are more stable than linear mRNAs and therefore attracting attention as a new synthetic mRNA that improves RNA persistence. However, specific introduction of mRNA into target cells has been difficult, and unintended protein expression in non-target cells may lead to reduced therapeutic efficacy and side effects in medical applications of mRNA. Therefore, it is necessary to develop a technology to control protein expression (gene expression) from cyclic RNA, but this has not been realized yet. The Saito laboratory started to work on the development of an RNA switch technology that can control gene expression of cyclic RNAs according to cell type. The research group synthesized cyclic RNAs that are intended to respond to endogenous miRNAs to regulate gene expression.

 by Kyoto University

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