Nature Communications (Mar 2022)
Combinatorial optimization of mRNA structure, stability, and translation for RNA-based therapeutics
- Kathrin Leppek,
- Gun Woo Byeon,
- Wipapat Kladwang,
- Hannah K. Wayment-Steele,
- Craig H. Kerr,
- Adele F. Xu,
- Do Soon Kim,
- Ved V. Topkar,
- Christian Choe,
- Daphna Rothschild,
- Gerald C. Tiu,
- Roger Wellington-Oguri,
- Kotaro Fujii,
- Eesha Sharma,
- Andrew M. Watkins,
- John J. Nicol,
- Jonathan Romano,
- Bojan Tunguz,
- Fernando Diaz,
- Hui Cai,
- Pengbo Guo,
- Jiewei Wu,
- Fanyu Meng,
- Shuai Shi,
- Eterna Participants,
- Philip R. Dormitzer,
- Alicia Solórzano,
- Maria Barna,
- Rhiju Das
Affiliations
- Kathrin Leppek
- Department of Genetics, Stanford University
- Gun Woo Byeon
- Department of Genetics, Stanford University
- Wipapat Kladwang
- Department of Biochemistry, Stanford University
- Hannah K. Wayment-Steele
- Department of Chemistry, Stanford University
- Craig H. Kerr
- Department of Genetics, Stanford University
- Adele F. Xu
- Department of Genetics, Stanford University
- Do Soon Kim
- Department of Biochemistry, Stanford University
- Ved V. Topkar
- Program in Biophysics, Stanford University
- Christian Choe
- Department of Bioengineering, Stanford University
- Daphna Rothschild
- Department of Genetics, Stanford University
- Gerald C. Tiu
- Department of Genetics, Stanford University
- Roger Wellington-Oguri
- Eterna Massive Open Laboratory, Stanford University
- Kotaro Fujii
- Department of Genetics, Stanford University
- Eesha Sharma
- Department of Biochemistry, Stanford University
- Andrew M. Watkins
- Department of Biochemistry, Stanford University
- John J. Nicol
- Eterna Massive Open Laboratory, Stanford University
- Jonathan Romano
- Eterna Massive Open Laboratory, Stanford University
- Bojan Tunguz
- Department of Biochemistry, Stanford University
- Fernando Diaz
- Pfizer Vaccine Research and Development
- Hui Cai
- Pfizer Vaccine Research and Development
- Pengbo Guo
- Pfizer Vaccine Research and Development
- Jiewei Wu
- Pfizer Vaccine Research and Development
- Fanyu Meng
- Pfizer Vaccine Research and Development
- Shuai Shi
- Pfizer Vaccine Research and Development
- Eterna Participants
- Eterna Massive Open Laboratory, Stanford University
- Philip R. Dormitzer
- Pfizer Vaccine Research and Development
- Alicia Solórzano
- Pfizer Vaccine Research and Development
- Maria Barna
- Department of Genetics, Stanford University
- Rhiju Das
- Department of Biochemistry, Stanford University
- DOI
- https://doi.org/10.1038/s41467-022-28776-w
- Journal volume & issue
-
Vol. 13,
no. 1
pp. 1 – 22
Abstract
The authors develop an RNA sequencing-based platform, PERSIST-seq, to simultaneously delineate in-cell mRNA stability, ribosome load, and in-solution stability of a diverse mRNA library to derive design principles for improved mRNA therapeutics.