Three Boston University biomedical engineers have created a genetic dimmer switch that can be used to turn on, shut off, or partially activate a genes function. Professor James Collins, Professor Charles Cantor and doctoral candidate Tara Deans invented the switch, which can be tuned to produce large or small quantities of protein, or none at all.

The research detailing their new switch, A Tunable Genetic Switch Based on RNAi and Repressor Proteins for Regulating Gene Expression in Mammalian Cells, appears in the July 27 issue of Cell.

This switch helps advance the field of synthetic biology, which rests on the premise that complex biological systems can be built by arranging components or standard parts, as an electrician would to build an electric light switch. Much work in the field to date uses bacteria or yeast, but the Boston University team used more complex mammalian cells, from hamsters and mice. The switch has several new design features that extend possible applications into areas from basic research to gene therapy.

There are a number of technologies available to regulate gene expression, but they each come with limitations, said Collins. One of the central problems is you cant get a really tight off state.

Even when genetic switches are turned off, a trickle of the protein that is meant to be repressed still gets made. Some genetic switches get around this by entirely snipping out a gene to stop production of a specific protein, but this approach is irreversible.

To overcome these challenges, Tara came up with a design that really combined two different technologies to repress or shut down gene expression, Collins added. We said, okay, weve got these two technologies, both that give a pretty good off, why not try to combine them together to get a really clear and strong off, said Collins.

The first strategy, a repressor protein, sits on DNA like a roadblock, preventing any gene product --
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Contact: Mike Seele
mseele@bu.edu
617-353-9766
Boston University
26-Jul-2007