Scientists reveal a technique that uses light to flip on individual genes in a cell.
This may help our bodies produce precise amounts of proteins to be used with drugs or control dosages in gene therapies. Or, cells engineered to carry the light switch could be implanted into patients to produce missing hormones.
All on demand!
The method involves linking the light-sensing molecular machinery in eyeballs to the gene-expression system in cells.
In response to strong light, melanopsin – a light-sensitive molecule on the surface of nerve cells in the retina – triggers a rush of calcium ions into neurons, leading to an electrical pulse. (That’s because melanopsin helps keep biological clocks in sync with the dusk and dawn schedule.)
So, Swiss researchers led by Martin Fussenegger of University of Basel created their own special light-sensitive cells:
- They transferred the gene for melanopsin into human kidney cells, and then irradiated them with blue lights (pictured above).
- But instead of an electrical pulse, here, those calcium ions kick off a cascade of reactions that activate a protein called NFAT.
- NFAT moves into the nucleus of cells and binds to DNA sequences, which then activates certain genes.
- By introducing a target gene with an NFAT promoter into the cells’ genome as well, the scientists can put that gene under the control of light, ScienceNOW explains. Switch on the light, and the cells start producing the protein that the gene encodes.
Then, the team tested their technique as a potential type 2 diabetes treatment: they coaxed cultured cells to produce just the right amount of a protein called shGLP-1, which helps control blood glucose levels.
They injected shGLP-1-expressing cells under the skin of mice. Illuminating them with blue-light pulses (pictured, right) for 48 hours increased the levels of both shGLP-1 and insulin, which controls sugar in blood.
The action of both proteins significantly tempered the rodents’ blood sugar levels following a shot of sugar.
In addition to insulin, the technology can potentially deliver other types of therapeutic proteins, such as human growth hormone, Fusseneger says. These proteins are produced by engineered cells and delivered by injection. “But now you could produce it in the patient and get the dosing right not by injection but by applying light.”
The study was published in Science today.
Images: Science/AAAS
