In Situ Imaging
Ventilated, bed-ridden patients are at great risk for acute lung injury or infection. A portable x-ray machine can tell that there’s something wrong—a shadow on the lung, perhaps—but not what that something is, and subsequent microbiological culture can take awhile. Yet for treatment to be effective, it should be initiated within about 24 hours—otherwise there is about a 60% rate of mortality.
Enter Edinburgh Molecular Imaging (EMI), which was incorporated in March. EMI is developing a system for fluorescent microscopy through a fiber optic cable, which is relatively easy to administer in already intubated patients.
Three types of molecular probes will be used: the first will fluoresce on contact with bacteria, the second differentiates between Gram-negative and Gram-positive bacteria, and the third detects methicillin-resistant Staphylococcus aureus. These can be dispensed in micro doses (subtherapeutic amounts) into the lung and imaged in less than 15 minutes.
These probes should be available for in vivo use in animals within a year. However, “in terms of probes actually coming out as clinical diagnostics, we’re talking about five years’ time,” the company reports.
The big idea behind BigDNA is to let the body produce its own proteins for vaccination. BigDNA’s strategy is to clone an antigen into bacteriophage λ. The phage is used to infect E. coli, which can then be grown up in large quantities. It’s then harvested, purified, and used to inoculate the animal, where it is picked up by monocytes. The monocytes break it down, transcribe the DNA, and express the encoded antigen on their surface.
Unlike a standard protein vaccine, DNA vaccines usually have a greater cellular component as well as an antibody response. “So you get a response that’s more similar to an actual infection than just to the proteins of the vaccine,” says Karen Jervis, Ph.D., the company’s commercial director.
DNA vaccines are also relatively inexpensive and quick to produce—an influenza vaccine could be available within four weeks of identifying the strain, for example, compared to the one-year lead time necessary with today’s technology. And, because the protein coat protects the DNA, the vaccines are also relatively stable at room temperature, obviating the need for a cold transport and storage chain.
BigDNA’s lead product, slated for clinical trials in 2013, codes for the same hepatitis B antigen that has been delivered in millions (if not billions) of inoculations.
“As a consequence, the clinical correlates of protection are extremely well characterized,” Dr. Jervis explains. “It is, therefore, the perfect candidate indication for our first product—what you see in the clinic will be attributable to the vaccine.” Experiments using an early version show a greater response in rabbits after one or two courses than does a three-course regimen of the standard protein vaccine.
Perhaps the most recognizable single name in Scottish biotech is Roslin.
BigDNA is located in the Roslin Biocentre in Roslin, a few kilometers outside of Edinburgh proper. Sheep Dolly, Polly, and Molly were cloned at the Roslin Institute, which moved to a new 500-researcher capacity building this year. The Roslin Foundation is a charity associated with the Roslin Institute and the University of Edinburgh.
Among other endeavors, the Roslin Foundation owns Roslin Cells, the mission of which is to supply undifferentiated stem cell lines for use in therapy, and to facilitate development of stem cell therapies.
It’s important that clinical-grade cells be procured, isolated, manipulated, and stored in ways that researchers and regulators are confident that they’re fit to be put into patients. Roslin Cells is very much about quality control; it assures that consent and procurement of the initial tissue is correct and well documented, and it writes everything down. “There are standard operating procedures for everything we do,” says CEO Aidan Courtney.
Once tissue is procured, Roslin Cells isolates the cells of interest and establishes a population of cells or a cell line that could be the starting material for a therapy.
Courtney makes no pretenses about doing the kind of ground-breaking work that gets reported in high-impact journals. Rather, Roslin Cells’ core competence is the ability to work with academics with an expertise in differentiating cells to a particular lineage—liver or endothelial cells, for example—to reduce theory down to a robust, solid, industrial process. “We’ve got a major GMP cell-processing facility that is embedded in European regulations.”
Later this year Roslin Cells will move its operations to the Scottish Center for Regenerative Medicine, where it will operate seven cleanrooms.