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Chemically Modified mocRNAs for Highly Efficient Protein Expression in Mammalian Cells
Name
acschembio.1c00569.pdf
Description
Published version
Size
8.76 MB
Format
Adobe PDF
Checksum (MD5)
e533f067a1be91556dae6be8233527e1
Author(s)
Aditham, Abhishek
Shi, Hailing
Guo, Jianting
Zeng, Hu
Zhou, Yiming
Wade, Sarah Dunn
Huang, Jiahao
Liu, Jia
Wang, Xiao
Date Issued
January 7, 2022
Journal
ACS Chemical Biology
Publisher
American Chemical Society (ACS)
Citation
Aditham, Abhishek, Shi, Hailing, Guo, Jianting, Zeng, Hu, Zhou, Yiming et al. 2022. "Chemically Modified mocRNAs for Highly Efficient Protein Expression in Mammalian Cells." ACS Chemical Biology.
Version
Final published version
Abstract
mRNA has recently been established as a new class of therapeutics, due to its programmability and ability to produce proteins of interest rapidly in vivo. Despite its demonstrated utility, mRNA as a protein expression platform remains limited by its translational capacity and RNA stability. Here, we introduce messenger-oligonucleotide conjugated RNAs (mocRNAs) to enable site-specific, robust, and modularized encoding of chemical modifications for highly efficient and stable protein expression. In mocRNA constructs, chemically synthesized oligonucleotides are ligated to the 3' terminus of mRNA substrates to protect poly(A) tails from degradation, without compromising their potency in stimulating translation. As a proof-of-concept, mocRNAs modified by deadenylase-resistant oligonucleotides result in augmented protein production by factors of 2-4 in human HeLa cells and by 10-fold in primary rat cortical neuronal cultures. By directly linking enzymatic and organic synthesis of mRNA, we envision that the mocRNA design will open new avenues to expand the chemical space and translational capacity of RNA-based vectors in basic research and therapeutic applications.
Terms of Use
Creative Commons Attribution-NonCommercial-NoDerivs License
Persistent DSpace Link
DOI of Published Version
10.1021/acschembio.1c00569
