Optimizing the use of in vitro transcribed SGK1-mRNA as a therapeutic tool to treat female infertility

Abstract Objectives Gene therapy has emerged as an encouraging therapeutic approach for several diseases. The use of plasmid DNA (pDNA) or viral vectors encoding proteins have yielded low efficacy in recent trials. Synthetic messenger RNA (mRNA), also known as in vitro transcribed mRNA (IVT-mRNA), i...

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Main Authors: Itishri Sahu, Fabienne Engelmann, Brian Weidensee, Harivignesh Ganesan, Sara Y. Brucker, Yogesh Singh, Madhuri S. Salker
Format: Article
Language:English
Published: BMC 2025-07-01
Series:BMC Research Notes
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Online Access:https://doi.org/10.1186/s13104-025-07346-5
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Summary:Abstract Objectives Gene therapy has emerged as an encouraging therapeutic approach for several diseases. The use of plasmid DNA (pDNA) or viral vectors encoding proteins have yielded low efficacy in recent trials. Synthetic messenger RNA (mRNA), also known as in vitro transcribed mRNA (IVT-mRNA), is a highly potent alternative. However, the use of IVT-mRNA in reproductive conditions remains scarce. Our previous work has demonstrated the involvement of endometrial serum- and glucocorticoid kinase 1 (SGK1), where it influences pregnancy outcomes in murine models. On this basis, we investigated the expression and function of human SGK1 encoded by IVT-mRNA in vitro. Results We show using flow cytometry, quantitative RT-PCR and immunoblotting, that IVT-mRNA has a superior transfection efficiency compared with pDNA. At protein level, we show that the constitutively active SGK1 variant (SGK1 S422D) could increase protein levels and that the inactive SGK1 variant (SGK1 K127A) could reduce SGK1 levels. This effect of SGK1 activity modulation could contribute to reprogramming endometrial cells and support a conducive environment for pregnancy.
ISSN:1756-0500