TR Editors' blog

Transparent Fish Provide a Window into Clogged Arteries

Genetically engineered zebrafish could provide a quick way to test new drugs to prevent dangerous plaque buildup in the heart.

Emily Singer 11/23/2011

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This zebrafish was engineered to carry a fluorescent antibody that binds to bad cholesterol.
Credit: UC San Diego School of Medicine

As you gorge on creamy potatoes and buttery pie this Thanksgiving, the effect on your arteries probably isn't top of mind. But for these newly engineered zebrafish, created by researchers at the University of California, San Diego, the effect of cholesterol is impossible to ignore. Researchers can directly observe the accumulation of LDL, or bad, cholesterol in the transparent fish.

During artherosclerosis, high levels of LDL cholesterol leads to plaque buildup in the arteries. If the plaque ruptures, it can trigger a blood clot, heart attack, or stroke. The transparent fish allow researchers to study the process more closely and test the effects of different drugs much more quickly than they can with other animals used to study heart disease.

They found that treating fish fed a high cholesterol diet with an antioxidant drug reversed the buildup of bad cholesterol just as well as putting the animals on a low-cholesterol diet.

"We saw the results in just 10 days working with the zebrafish model. A similar experiment in mice took six months to complete," said first author Longhou Fang, in a press release from the university.The research will be published in the December 1 issue of the Journal of Clinical Investigation.

To create the fish, researchers inserted a gene for an antibody that binds to certain forms of LDL cholesterol. The genetic insert also carries the gene for green fluorescent protein, making the antibody glow.

Sculpting Tissues with Magnets

Cells treated with magnetic nanoparticles can be held in tissue-like 3-D shapes.

Katherine Bourzac 03/15/2010

Glioblastoma cells cultured in 3D with the Bio-Assembler.
Credit: Nano3D Biosciences

Being able to grow more realistic liver, heart, and other tissues in the lab could provide a new lease on life for patients waiting on the transplant list--and lead to more realistic systems for testing drugs. But tissue engineers have found that mimicking these complex, three-dimensional structures in the lab is difficult. Part of what's holding them up are flat, two-dimensional tissue culture systems that grow cells in an environment very different from that inside the body.

Now researchers at Rice University and the MD Anderson Cancer Center in Houston have developed a simple way to make cells form 3-D structures. They developed a gel made up of a polymer, iron oxide nanoparticles, and engineered viruses called phage. When cells are added to this mixture, the phage cause them to absorb the magnetic particles. The Houston group showed that they could use a weak magnet to hold magnetized brain cancer cells in a 3-D suspension. Gene-expression studies showed that these suspended cells behave more naturally than a control group grown on a conventional flat surface: the cancer cells were producing a mix of proteins very similar to what they produce in the body. These results are described in Nature Nanotechnology this week.

The magnetizing gel has been licensed to a startup company, Nano3D Bioscience, which will run tests to compare the technology other methods for making 3-D tissues.

FDA Approves First "Pharm" Animals

The first drug on the market made by animals carrying a human gene is being produced in goats' milk.

Katherine Bourzac 02/09/2009

Last Friday, the U.S. Food and Drug Administration approved the first drug made by animals carrying a human gene. The drug, a protein called antithrombin that prevents fatal blood clots, is excreted by goats into their milk, and then purified. Though patients have been taking drugs made by animals for many years now, including insulin (and more notoriously, heparin), these goats are the first herd of animals genetically engineered to serve as drug factories. The animals were bred by the company GTC Biotherapeutics and are maintained on a farm in Massachusetts.

The New York Times reports that the approval will open the way for other such drugs:

The F.D.A.'s move "really takes away one of the biggest issues that have always been on the table, which is how do regulatory agencies view this kind of technology," said Samir Singh, president of the American operations of Pharming, another company using such technology.

Two years ago I wrote about transgenic chickens that produce high levels of protein drugs in their eggs. At that time, researchers speculated that poultry would be easier to "pharm" than mammals. However, both chicken-pharming companies I mentioned in the 2007 story appear to have gone under. In August the SEC revoked Viragen's stock, and Avigenics' website has disappeared.

The Times reports that animal-rights groups are worried; the story quotes assurances from the company that none of the goats' milk or flesh will make it into the food supply. Making drugs in giant vats of microbes called bioreactors doesn't raise quite as many issues for animal-rights and bioethics groups as does pharming, but it has some limitations. The reactors are expensive to maintain, and bacteria can't make every protein drug, because they simply can't perform the extensive protein-processing of which animal cells are capable.

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