Who needs NASA? Launching genes with lasers in space-travelled fish

Inside the cell genes are launched from promoters on our DNA.
(photo of space shuttle Atlantis)

NASA has its sights on launching rockets into space using lasers. "What if..." they're wondering, "shuttles could be sent up using laser beams to heat their fuel from the ground?"

Biophysicists in Japan have had a similar idea. They've successfully used lasers to 'launch' genes inside living creatures, with a little help from nanotechnology. If this process works in humans, future battles with cancer may be fought by remote control.

Deep within our cells, genes are launched into action from promoters, sequences of DNA where movable machinery assembles to fire copies of a gene, called messenger RNAs (mRNAs), from the nucleus to the cytoplasm.

Promoter ’launch pads’ are triggered by different things – stresses or chemicals or signals from outside the cell. Some promoters are heat sensitive, firing off mRNAs in response to fever or infection. Arriving in the cytoplasm, their mission is to build proteins to defend the cell from invaders such as viruses.

New research published recently in PNAS, describes a way of using laser light to trigger these 'heat shock' promoters from above the skin of living organisms. It's a first step towards launching our own genetic defences to disease from outside the human body.

Could lasers be used to fire mRNAs out from
the nucleus to fight diseases?
(photo: Space shuttle Atlantis from plane, Ryan Graff)

To develop these new pyrotechnics, Eiliro Miyako and colleagues injected carbon nanoparticles called nanohorns into medaka fish, Oryzias latipes. These fish are no strangers to laboratories. They've even been to space (and were the first Earthly vertebrates to reproduce in orbit).

Nanohorns, molecule-thin sheets of carbon folded into cone shapes, have huge potential for scooping up and delivering drugs inside cells and tissues. But it was something else about these tiny metal structures (which measure around 1/100000 cm across) that excited Dr Miyako and his team: nanohorns convert laser light energy into heat.

With a microscopic fuel source in hand the team from collaborating research institutes in Japan, set about building a DNA launch pad.

They pieced together DNA in the lab, placing the gene for a green fluorescent protein (GFP) next to a man-made heat shock promoter. After transferring the whole thing into the cells of the medaka fish, it was time for launch!

A low-powered laser beam was focused beneath the fish's skin. The carbon nanohorns absorbed the laser's energy, emitting it as heat. The surrounding tissue began to warm up. At a temperature of 42°C the heat shock promoters fired into life, launching the GFP gene. Minutes later the cells in the fish were glowing green. Genes had been successfully launched from outside a living body.

Medaka, the first vertebrate to reproduce in space.
In this study its genes were launched by remote control.

Dr Miyako writes "This work is a proof-of-principle study demonstrating that... gene expression can be mediated by the photothermal properties of nanocarbons."

 He believes that they could be used "in various biological fields, including analysis of cell signaling within organisms, investigation of genetic mechanisms, and development of unique cell therapies and tissue engineering techniques."



Makes you wonder which will come first - the fire laser-propelled rocket to the moon, or the first cancerous cell killed by remote control?

What does this mean for me?

This study was not simply about making glowing fish. As Dr Miyato says, this is a proof of principle. In the future, lasers might be used to trigger specific genes inside the human body, boosting the body's response to infection, or triggering cell death in cancer cells. This could compliment drug-based approaches aiming to manipulate genes and proteins in a similar way. The team have also used nanohorns to trigger genes inside living mice and found no signs of toxicity or adverse reaction to the particles, which is encouraging for future trials.

What does this mean for science?

Remote control of gene expression has been achieved before, but this study is the first to use near infrared light (NIR, with wavelengths between 0.7- 2.5um). NIR light lies inside the "optical window" of biological tissue (0.6- 1.1um) and is able to penetrate over 10cm deep. This study adds to the - already impressive - list of potential uses for metal nanoparticles in biology including drug delivery, tissue scaffolding,  the detection of harmful pathogens and improved MRI images.

Reference (free to download via Open Access!):

Miyako, E., Deguchi, T., Nakajima, Y., Yudasaka, M., Hagihara, Y., Horie, M., Shichiri, M., Higuchi, Y., Yamashita, F., Hashida, M., Shigeri, Y., Yoshida, Y., & Iijima, S. (2012). Photothermic regulation of gene expression triggered by laser-induced carbon nanohorns Proceedings of the National Academy of Sciences, 109 (19), 7523-7528 DOI: 10.1073/pnas.1204391109