Biocatalytic assembly of chemically modified oligonucleotides

With renewed interest in therapeutic oligonucleotides, and at the same time the pharmaceutical industry set itself ambitious sustainability goals, there is a strong interest to investigate next-generation synthesis methods for these highly modified oligonucleotides. We herein report an RNA ligase catalyzed assembly of multiple, short oligonucleotides in aqueous solution to generate an siRNA product. A conversion of the non-native substrates to the desired product of 40 – 80 % was achieved.