Researchers from the University of Bath and Cardiff University have developed a biological switch that reliably triggers protein expression and enables the control of genome editing tools.
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The new method, which can be applied to any protein in any animal, involves the use of a cheap, abundant, non-toxic and potentially environmentally friendly amino acid called BOC.
Unlike other switching methods, this new switch does not involve the use of antibiotics, therefore eliminating the risk of selecting for antimicrobial resistance. It also is not “leaky” − a term that refers to proteins being expressed when the switch is not turned “on.”
The researchers showed that the switch was effective in both cultured cells and in mouse embryos, without any protein expression being detected when BOC was not present. As reported in the journal Scientific Reports, the technique builds on a principle called genetic code expansion.
Professor Tony Perry and colleagues demonstrated this principle using mice that had been engineered to carry a gene that causes their skin to fluoresce green once exposed to UV light.
When the expansion toolkit adapted for gene editing was present in embryos from the mice, their DNA was edited such that the fluorescence gene was removed.
However, the gene was only successfully removed in the presence of BOC; without BOC, the genome editing did not take place. The embryos that were successfully edited grew into mice that did not glow green, but when BOC was not present, the mice continued to fluoresce.
The method has the potential to control an array of biological processes in the test-tube, in animals or in both. It could be used to study the effects proteins have on aging cells, for example, or to activate proteins involved in regenerative processes.
One possible application would be to use the switch in gene drives. The CRISPR-Cas 9 system could be used in gene drive technology to ensure that all offspring of a reproducing species inherits a certain gene sequence to avoid the 50% inheritance risk that would otherwise result from reproduction.
For example, scientists have conducted trials that use gene drives to spread genes among mosquitoes that render the females infertile, potentially eradicating the transmission of malaria.
Perry says that what sets this study apart from others is its potential to provide an environmentally friendly switch across large distances, which no previous method really enables.
Gene editing has enormous potential across biological science, from biomedicine to food security, in insects, plants and animals."
Professor Tony Perry
Co-author Yuhsuan Tsai says BOC provides a promising and attractive way of controling gene editing and that the team is now working on addressing the remaining challenges and ironing out wrinkles in the system.