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Variety of Nucleotide Polymerase Mutants Aiming to Synthesize Modified RNA
Author(s) -
Ohashi Sana,
Hashiya Fumitaka,
Abe Hiroshi
Publication year - 2021
Publication title -
chembiochem
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.05
H-Index - 126
eISSN - 1439-7633
pISSN - 1439-4227
DOI - 10.1002/cbic.202100004
Subject(s) - rna , polymerase , rna dependent rna polymerase , nucleotide , aptamer , transcription (linguistics) , nucleoside , rna editing , chemistry , rna polymerase , biochemistry , biology , computational biology , dna , combinatorial chemistry , microbiology and biotechnology , gene , linguistics , philosophy
Significant efforts have been made to develop therapeutic RNA aptamers that exploit synthetic RNA to capture target molecules. However, ensuring RNA aptamers are resistant against intrinsic nucleases remains an issue and restricts their use as therapeutics. Introduction of chemical modifications to the 2′ sugar moiety of RNA improves their stability effectively and can be achieved by chemical synthesis using modified phosphoramidites; however, this approach is not suitable for preparing long RNA molecules. Although recombinant nucleotide polymerases can transcribe RNA, these polymerases cannot synthesize modified RNA because they do not recognize 2′ modified nucleoside triphosphates. In this review, we focus on several polymerase mutants that tolerate substrates containing modifications of the 2′ sugar moiety to synthesize RNA, and the problems that must be overcome to prepare chemically modified RNA with high efficacy by in vitro transcription.