Genetically engineered bacteria treatintestinal disease
Context: Finding ways to get drugs to the right part of the body is a constant challenge for drugmakers. The intestines would seem easier to treat than other areas, as drugs taken orally should eventually arrive there. But a number of promising drugs for the treatment of colitis, an intensely uncomfortable infl ammation of the large intestine, become waylaid in the mucus of the small intestine and never reach their target. Now, a group of researchers led by Lothar Steidler from Ghent University in Belgium has genetically modified bacteria to secrete such a drug as they travel through the gut.
Methods and Results: The researchers engineered Lactococcus lactis so that it would produce trefoil factors, shamrock-shaped proteins that hasten healing and protect the gut from injury. The modified bacteria proved more effective than the purified protein alone at preventing and treating colitis in mice. Outside the body, the bacteria do not survive.
Why it matters: The use of genetically modified (GM) organisms as drug delivery devices is moving toward the mainstream. Another GM bacterium produced by these researchers, one that secretes the anti-inflammatory drug interleukin-10, is being tested in European clinical trials as a treatment for infl ammatory bowel disease. Other GM bacteria, to be delivered to the nose and vaginal tract, are being studied to prevent infectious disease. Still another may deliver a cancer vaccine. In the 1980s and ’90s, recombinant DNA technology ushered in an era of new protein drugs; despite substantial regulatory and technical obstacles, bacteria may prove an effective way to deliver them.
Source: Vandenbroucke, K. et al. (2004) Active delivery of trefoil factors by genetically modifi ed Lactococcus lactis prevents and heals acute colitis in mice. Gastroenterology 127:502-513.