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Research interests
The McRae lab is currently funded by a 5-year CPRIT recruitment grant to perform structure-based design of RNA therapeutics.
RNA therapeutics are emerging as a new way of targeting previously un-druggable therapeutic targets, and their full potential has yet to be realized. The focus thus far has been on RNA sequence, whereas next generation therapies will also utilize RNA structure. Current mRNA therapy design has optimized 5’ and 3’ untranslated regions (UTRS) as well as the coding sequence to maximize the translational output of mRNA. The 5’ and 3’ UTR sequences have been borrowed from naturally occurring sequences that have abundant translational output, resulting in an mRNA therapeutic that is ubiquitously expressed wherever the mRNA encounters translational machinery. However, key property of 5’ and 3’ UTRs is their complex 3D structure that allows them to regulate protein expression in a tightly controlled manner. Harnessing the full regulatory power of 5’ and 3’ UTRs for translational control of mRNA therapeutics would allow for expression of the mRNA payload only in the correct cellular context and reduce off-target effects. Achieving this regulatory specificity requires an understanding of RNA structural biology and the molecular interactions that govern the structure of 5’ and 3’ UTRs. Our research group uses cryo-EM structure determination and the design principles from the RNA origami method to modify RNA structures to improve the currently used 5’ and 3’ UTRs of mRNA therapies. By exploiting the cancer cell environment to enable cell state-specific expression and stabilization of the mRNA we hope to improve the efficacy of mRNA therapies for immunizing against and treating cancers.
External positions
Assistant Professor of Biochemistry in Medicine, Weill Cornell Medical College
Dec 1 2023 → …
Research Area Keywords
- Heart & Vascular
- Cancer
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Collaborations and top research areas from the last five years
Projects
- 1 Active
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An RNA origami robot that traps and releases a fluorescent aptamer
Vallina, N. S., McRae, E. K. S., Geary, C. & Andersen, E. S., Mar 22 2024, In: Science Advances. 10, 12, p. eadk1250 eadk1250.Research output: Contribution to journal › Article › peer-review
Open Access1 Scopus citations -
Cryo-EM structure and functional landscape of an RNA polymerase ribozyme
McRae, E. K. S., Wan, C. J. K., Kristoffersen, E. L., Hansen, K., Gianni, E., Gallego, I., Curran, J. F., Attwater, J., Holliger, P. & Andersen, E. S., Jan 16 2024, In: Proceedings of the National Academy of Sciences of the United States of America. 121, 3, p. e2313332121 e2313332121.Research output: Contribution to journal › Article › peer-review
Open Access4 Scopus citations -
An RNA Paranemic Crossover Triangle as A 3D Module for Cotranscriptional Nanoassembly
Sampedro Vallina, N., McRae, E. K. S., Geary, C. & Andersen, E. S., Mar 29 2023, In: Small. 19, 13, p. e2204651 2204651.Research output: Contribution to journal › Article › peer-review
Open Access5 Scopus citations -
RNA origami scaffolds facilitate cryo-EM characterization of a Broccoli-Pepper aptamer FRET pair
Sampedro Vallina, N., McRae, E. K. S., Hansen, B. K., Boussebayle, A. & Andersen, E. S., May 22 2023, In: Nucleic Acids Research. 51, 9, p. 4613-4624 12 p.Research output: Contribution to journal › Article › peer-review
Open Access14 Scopus citations -
RNA target highlights in CASP15: Evaluation of predicted models by structure providers
Kretsch, R. C., Andersen, E. S., Bujnicki, J. M., Chiu, W., Das, R., Luo, B., Masquida, B., McRae, E. K. S., Schroeder, G. M., Su, Z., Wedekind, J. E., Xu, L., Zhang, K., Zheludev, I. N., Moult, J. & Kryshtafovych, A., Dec 2023, In: Proteins: Structure, Function and Bioinformatics. 91, 12, p. 1600-1615 16 p.Research output: Contribution to journal › Article › peer-review
Open Access9 Scopus citations