Universität zu Köln

Bornewasser, Lisa ORCID: 0000-0002-3890-107X, Domnick, Christof and Kath-Schorr, Stephanie (2022). Stronger together for in-cell translation: natural and unnatural base modified mRNA. Chem. Sci., 13 (17). S. 4753 - 4763. CAMBRIDGE: ROYAL SOC CHEMISTRY. ISSN 2041-6539

Full text not available from this repository.

Abstract

The preparation of highly modified mRNAs and visualization of their cellular distribution are challenging. We report in-cell application of in vitro transcribed mRNA containing natural base modifications and site-specifically introduced artificial nucleotides. Click chemistry on mRNA allows visualization in cells with excellent signal intensities. While non-specific introduction of reporter groups often leads to loss in mRNA functionality, we combined the benefits from site-specificity in the 3 '-UTR incorporated unnatural nucleotides with the improved translation efficiency of the natural base modifications psi and 5mC. A series of experiments is described to observe, quantify and verify mRNA functionality. This approach represents a new way to visualize mRNA delivery into cells and monitor its spread on a cellular level and translation efficiency. We observed increased protein expression from this twofold chemically modified, artificial mRNA counterbalancing a reduced transfection rate. This synergetic effect can be exploited as a powerful tool for future research on mRNA therapeutics.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Bornewasser, Lisa UNSPECIFIED orcid.org/0000-0002-3890-107X UNSPECIFIED Domnick, Christof UNSPECIFIED UNSPECIFIED UNSPECIFIED Kath-Schorr, Stephanie UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-658195
DOI:	10.1039/d2sc00670g
Journal or Publication Title:	Chem. Sci.
Volume:	13
Number:	17
Page Range:	S. 4753 - 4763
Date:	2022
Publisher:	ROYAL SOC CHEMISTRY
Place of Publication:	CAMBRIDGE
ISSN:	2041-6539
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language GENETIC ALPHABET; ENHANCES TRANSLATION; PSEUDOURIDINE; EXPANSION; PAIR; TRANSCRIPTION; SYSTEM; DNA Multiple languages Chemistry, Multidisciplinary Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/65819