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Naturally occurring DNA is encoded by the four nucleobases adenine, cytosine, guanine and thymine. Yet minor chemical modifications to these bases, such as methylation, can significantly alter DNA function, and more drastic changes, such as replacement with unnatural base pairs, could expand its function. In order to realize the full potential of DNA in therapeutic and synthetic biology applications, our ability to 'write' long modified DNA in a controlled manner must be improved. This review highlights methods currently used for the synthesis of moderately long chemically modified nucleic acids (up to 1000 bp), their limitations and areas for future expansion.

Original publication




Journal article


Biochem Soc Trans

Publication Date





709 - 715


chemical ligation, modified triphosphates, oligonucleotide synthesis, Adenine, Cytosine, DNA, DNA Ligases, DNA-Directed DNA Polymerase, Guanine, Oligonucleotides, Polymerase Chain Reaction, Thymine