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Synthetic RNAissance™ Genes Created by DNA2.0 Enable Key Research

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DNA2.0 has announced that the company’s RNAissance genes had been used to shed new light on the mechanisms that ensure that each daughter cell receives a full complement of genetic material when cells divide.

The study, published this week in Nature Cell Biology, was a collaboration between DNA2.0 and researchers in Dr. Jonathon Pines’ group at the Wellcome/CR UK Gurdon Institute and Department of Zoology at Cambridge.

DNA2.0’s RNAissance genes are widely used to ensure that phenotypes obtained when cells are treated with RNAi are not the unintended result of off-target effects, the company says. For the work reported in Nature Cell Biology, Dr. Pines went a step further. He made RNAi-resistant versions of both a wildtype and a mutated protein (Cdc20).

In the mutated version, all 23 lysines found in the wildtype protein were changed to arginine, a change that prevented the mutant Cdc20 from becoming ubiquitinated. By eliminating the natural Cdc20 from cells using RNAi, the Cambridge group was able to show that ubiquitination of Cdc20 is required to prevent a cell from dividing before all of its chromosomes are lined up on the mitotic spindle. This cell cycle checkpoint is essential to prevent serious genetic damage in animals from yeast to humans.

“We were delighted to help Dr. Pines by designing and making our RNAissance genes,” said Dr. Jeremy Minshull, the DNA2.0 coauthor of the study. “Making RNAi-resistant genes that encode mutant versions of cellular proteins has the potential to help us understand the molecular details of many biological processes, as Dr Pines’ group has so elegantly shown.”

Eliminating the natural copy of a protein and replacing it with a mutated version has previously been possible only through genetic manipulations that are largely restricted to microbial systems. Researchers now have a tool to aid them in studying the molecular basis of cellular phenotypes that even allows the modification of genes and proteins that are essential for a cell’s survival.