A mouthful of gene therapy.

Bruce Baum wants to help people salivate. As part of that unusual effort, the investigator at the National Institute of Dental Research in Bethesda, Md., has for the last few years applied the emerging tools of gene therapy to salivary glands.

In 1994, Baum and his colleagues showed in test-tube experiments that certain viruses can ferry functioning genes into the two primary cell types of the salivary glands, the acinar and ductal cells. Acinar cells release salt and fluids, while ductal cells absorb salt and are impermeable to water.

Baum's research may be useful for patients who lack acinar cells and consequently can't produce enough saliva. Radiation treatments given for head and neck tumors are deadlier to acinar cells than ductal cells, for example.

An autoimmune disorder called Sjogren's syndrome vigorously targets acinar cells as well.

Baum's group has taken the first steps toward restoring such ravaged salivary glands to health. Using viruses as delivery vehicles, they've added a gene to ductal cells that may transform them into acinarlike cells. The gene encodes a protein called a water channel, which normally resides within the outer membranes of cells. If ductal cells made these proteins, they might secrete water and salts, as acinar cells do.

In the test tube, the genetically engineered ductal cells indeed become water permeable, reports Baum. His group next plans to transfer the gene into the ductal cells of live animals and monitor their saliva production.

In addition to more saliva, Baum would like to make better saliva. His group has recently begun attempts at therapy with a gene encoding a small protein called histatin. Histatin is secreted into saliva and protects against fungal infections, says Baum. The team aims to have the salivary glands make more of the protein, which might protect people with devastated immune systems, such as AIDS patients, from the many mouth infections they suffer.

The investigators have already engineered cells in the lab to make large quantities of histatin. "We get buckets of the stuff," says Baum. The next question is whether mice that make extra histatin in saliva will be protected from infection.