Issue 10, 2022

Efficient synthesis and replication of diverse sequence libraries composed of biostable nucleic acid analogues

Abstract

Functional nucleic acids can be evolved in vitro using cycles of selection and amplification, starting from diverse-sequence libraries, which are typically restricted to natural or partially-modified polymer chemistries. Here, we describe the efficient DNA-templated synthesis and reverse transcription of libraries entirely composed of serum nuclease resistant alternative nucleic acid chemistries validated in nucleic acid therapeutics; locked nucleic acid (LNA), 2′-O-methyl-RNA (2′OMe-RNA), or mixtures of the two. We evaluate yield and diversity of synthesised libraries and measure the aggregate error rate of a selection cycle. We find that in addition to pure 2′-O-methyl-RNA and LNA, several 2′OMe-RNA/LNA blends seem suitable and promising for discovery of biostable functional nucleic acids for biomedical applications.

Graphical abstract: Efficient synthesis and replication of diverse sequence libraries composed of biostable nucleic acid analogues

Supplementary files

Article information

Article type
Communication
Submitted
09 feb. 2022
Accepted
15 apr. 2022
First published
30 ágú. 2022
This article is Open Access
Creative Commons BY license

RSC Chem. Biol., 2022,3, 1209-1215

Efficient synthesis and replication of diverse sequence libraries composed of biostable nucleic acid analogues

J. R. D. Hervey, N. Freund, G. Houlihan, G. Dhaliwal, P. Holliger and A. I. Taylor, RSC Chem. Biol., 2022, 3, 1209 DOI: 10.1039/D2CB00035K

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