Circular RNAs (circRNAs) are an attractive alternative to linear mRNAs due to their enhanced stability to exonucleases and lower production costs. Efficient and prolonged IRES-driven translation of circRNA was demonstrated in vitro and in mice, yet controversial data on immunogenicity of in vitro produced circRNAs that affects their expression were collected by different groups over the last few years.
PhD project description
The aim of this project is to develop a method of efficient production of low immunogenic, highly translatable circular mRNA for tissue-specific expression.
Required profile of the candidate
We are seeking a highly motivated candidate with a strong interest in RNA biology, who enjoys solving challenging scientific questions, is independent and able to work in the team.
A profound theoretical and practical knowledge in biochemical and molecular biology methods, and cell culture experience are welcome.
Publications relevant to the project
Chen R, Wang SK, Belk JA, Amaya L, Li Z, Cardenas A, Abe BT, Chen CK, Wender PA, Chang HY. Engineering circular RNA for enhanced protein production. Nat Biotechnol. 2023 Feb;41(2):262-272. doi: 10.1038/s41587-022-01393-0
Liu CX, Guo SK, Nan F, Xu YF, Yang L, Chen LL. RNA circles with minimized immunogenicity as potent PKR inhibitors. Mol Cell. 2022 Jan 20;82(2):420-434.e6. doi: 10.1016/j.molcel.2021.11.019
Qu L, Yi Z, Shen Y, Lin L, Chen F, Xu Y, Wu Z, Tang H, Zhang X, Tian F, Wang C, Xiao X, Dong X, Guo L, Lu S, Yang C, Tang C, Yang Y, Yu W, Wang J, Zhou Y, Huang Q, Yisimayi A, Liu S, Huang W, Cao Y, Wang Y, Zhou Z, Peng X, Wang J, Xie XS, Wei W. Circular RNA vaccines against SARS-CoV-2 and emerging variants. Cell. 2022 May 12;185(10):1728-1744.e16. doi: 10.1016/j.cell.2022.03.044
Wesselhoeft RA, Kowalski PS, Anderson DG. Engineering circular RNA for potent and stable translation in eukaryotic cells. Nat Commun. 2018 Jul 6;9(1):2629. doi: 0.1038/s41467-018-05096-6
Wesselhoeft RA, Kowalski PS, Parker-Hale FC, Huang Y, Bisaria N, Anderson DG. RNA Circularization Diminishes Immunogenicity and Can Extend Translation Duration In Vivo. Mol Cell. 2019 May 2;74(3):508-520.e4. doi: 10.1016/j.molcel.2019.02.015