Modified functional ONs will be synthesized. These include modifications with porphyrins, furan, cholesterol, lipids, m3G-CAP and triphosphates. Green chemistry aspects will be addressed by using chemoenzymatic syntheses, using novel enzymes created by directed protein evolution at ultrahigh throughput in droplets. The functional ONs will be designed to detect genetic disorders with ultra-high sensitivity, to stabilise secondary structures such as GQs and triplexes, cross-link intracellular targets such as miRNAs, for mapping disease relevant genes.