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Apr 23, 2012

Redefining Oligonucleotide Production(2012/4/15)

GEN(Genetic Engineering & Biotechnology News) Feature Articles: Apr 15, 2012 (Vol. 32, No. 8)

Redefining Oligonucleotide Production Neil McKenna, Ph.D.
Blockmer Technology Other companies represented at the meeting are developing chemical strategies to streamline the oligonucleotide synthesis process in order to reduce costs. Kyeong Eun Jung, Ph.D., senior director of oligonucleotide research and development at ST Pharm Co. (formerly Samchully Pharmaceutical) cites blockmer technology as a promising approach to more efficient oligonucleotide synthesis.

Conventional oligonucleotide synthesis involves the sequential coupling of monomeric nucleoside phosphoramidites. In the blockmer synthetic strategy, an oligonucleotide analog is generated by sequential coupling of short protected oligomers or blocks (for example, a dinucleotide) on a solid support. Advantages of this approach include a smaller number of synthesis cycles required to prepare an oligonucleotide, saving time and reducing the amount of starting reagent required.

“During synthesis of a 21 mer anticancer siRNA targeting noxin-like UV-induced anti-apoptotic protein, we reduced the number of coupling steps from 20 to 10,” says Dr. Jung. Another advantage is increased purity. “We have found that incorporation of a single dimer into a 21 mer siRNA can result in a 10% to 20% increase in purity,” he adds.

STPharm is also investigating the feasibility of more efficient recovery of phosphoramidite dimers as a means of reducing the costs of oligonucleotide synthesis.