From CPG to hybrid support: Review on the approaches in nucleic acids synthesis in various media

Solid-phase synthesis is, to date, the preferred method for the manufacture of oligonucleotides, in quantities ranging from a few micrograms for research purposes to several kilograms for therapeutic or commercial use. But for large-scale oligonucleotide manufacture, scaling up and hazardous waste production pose challenges that necessitate the investigation of alternate synthetic techniques. Despite the disadvantages of glass supports, using soluble supports as a substitute presents difficulties because of their high overall yield and complex purification steps. To address these challenges, various independent approaches have been developed; however, other problems such as insufficient cycle efficiency and synthesis of oligonucleotide chains of desired length continue to exist. In this study, we present a review of the current developments, advantages, and difficulties of recently reported alternatives to supports based on controlled pore glass, and discuss the importance of a support choice to resolve issues arising during oligonucleotide synthesis.