Biodegradable polymers deliver DNA to cells
The biggest challenge to the field of gene therapy remains the problem of delivery. Replacing faulty genes with normal ones in cells to treat disease requires safe methods for getting the therapeutic DNA into diseased cells. Viruses have been most commonly used for gene delivery, but a spate of leukemias in one French gene therapy trial and the death of a young man in a 1999 Philadelphia study have left researchers looking for better, safer vehicles.
Taking an engineering approach, Robert Langer of MIT and his colleagues have been developing synthetic polymers with the aim of supplying DNA to cells in a nontoxic, biodegradable package. Their newest polymers, described in this week’s issue of the Journal of the American Chemical Society, bind free DNA to form highly stable nanoparticles that are readily taken up by cells. Conditions inside the cell appear to favor the release of the DNA and the degradation of the polymer.
The work shows that the polymers delivered DNA to human cells as efficiently as the best research reagents available. And they are less toxic. Previous polymers developed by Langer and other researchers delivered less DNA to fewer cells.
The polymers are long strings of positively charged groups that grab onto highly negatively charged DNA. But the novel structures also allow for the easy attachment of other kinds of chemicals, including sugars, amino acids, and proteins. The researchers took advantage of this feature to improve the naked polymer. By adding positively charged amino acids, they showed that they could bind more DNA to the polymer, improving its efficiency in ferrying genes to cells.
The researchers also showed that they could tag the polymer with a short peptide that recognizes a specific receptor protein on the surface of blood vessel cells. This opens the door to the targeting of, for example, anticancer agents to blood vessels that feed tumors. Experiments underway will show whether the tagged particle will selectively enter those cells.
This is your brain with a migraine
Why people get migraine headaches remains a mystery, even though about 15 percent of the population suffers from this severe and sometimes disabling condition.
One contributing factor to migraines could be structural differences in the brain, according to work published this week in PLoS Medicine from Nouchine Hadjikhani and colleagues at Harvard Medical School and the Martinos Center for Biomedical Imaging at Massachusetts General Hospital. Using magnetic resonance imaging (MRI), the researchers discovered that people with migraines have physical changes in two related brain regions responsible for processing visual information. The study doesn’t say for sure if the changes are a cause or an effect of the migraines, but the abnormalities could account for some of the odd neurological symptoms experienced by some migraine sufferers.
Those symptoms include aura or preheadache visual disturbances, such as flashing lights, zigzag lines, and the experience of blind spots. Not all people with migraine experience aura, but they all have abnormal perception of movement, which often leads to motion sickness.
Given these migraine symptoms, the investigators decided to take a close look at the regions in the brain that handle visual inputs. They scanned the brains of 12 subjects who have migraines with aura, 12 with migraines without aura, and 15 normal controls. Performing two kinds of MRI allowed the researchers to pick up subtle changes. They found that migraine patients, whether they experienced aura or not, had a thickening of the outer brain layer, the cortex, in the visual areas of the brain. They also displayed abnormalities in their connections to adjacent regions compared to the control subjects.
For the first time, researchers have pinpointed a structural brain change in migraine sufferers, and finding the same changes in patients with or without aura indicates that these distinct manifestations of headache are in fact the same disease.
Endoscopes get smaller to go farther
Researchers at the Wellman Center for Photomedicine at Massachusetts General Hospital have developed a flexible fiber-optic probe, slightly thicker than a human hair, which can provide three-dimensional, high-resolution images of the body’s innermost cavities.
In a report published this week in Nature, Guillermo Tearney and colleagues demonstrate a prototype of the diminutive instrument, which uses a single optical fiber to deliver real-time images taken in spaces as small as a mouse’s belly. In their work, the researchers inserted the probe into the abdominal cavity of a mouse using a thin needle. The device clearly revealed tiny tumors, just a few millimeters in diameter, on the inner abdominal wall.
Endoscopes—flexible probes that doctors thread into body cavities—make diagnostic procedures and surgeries cheaper and less invasive. But one limitation of endoscopy has been the size of the devices. The traditional combination of a small lamp and a camera creates a cord the width of a pencil. This is fine for colonoscopies, but is too large to access smaller internal cavities. Smaller scopes, consisting of bundled optical fibers, have suffered from low resolution.
To miniaturize the instrument while maintaining resolution, the researchers went with a single fiber and a multicolored light source. After shining multiple wavelengths of light onto the tissue surface, the fiber transmitted the reflected light to external instruments for analysis.
With its flexibility and smaller size, the endoscope may allow physicians to venture more confidently into tight spaces like mammary ducts, Fallopian tubes, and delicate parts of the nervous system. The technique could also be useful in children and even for fetal procedures, and may enable delicate diagnostic and microsurgical procedures in currently inaccessible areas of the body.
