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Richard Mulligan, PhD

An "on-off" switch for genes
Researchers led by Richard Mulligan, PhD, director of Gene Therapy Research at Children's Hospital Boston, have created a simple system for turning genes on and off that may have major implications for medicine. With this technique, shown to work in mice, a gene could be activated by a drug or even by natural conditions in the body. For example, in a diabetic, a gene governing insulin production could be made to respond to a spike in blood sugar.

The technique involves inserting a special DNA sequence into a patient's own gene or one introduced by gene therapy. This sequence encodes a ribozyme, a snippet of genetic material that spontaneously cuts itself in two. When this cutting happens, the gene can't make the protein it's programmed to make. Inhibiting the cutting—as with a drug—turns the gene on when it's needed.

"Current gene-regulation methods are more complex and require an "activating" protein that can cause side effects," says Mulligan. "The ribozyme-based system is easier to turn on and off, allowing a treatment to be halted for safety reasons, and is more adaptable to different therapeutic uses." Laising Yen, PhD, of Molecular Medicine, was first author on the study, reported in the September 23 Nature.

Igor Splawski, PhD (left), and Mark Keating, MD.

Genetic syndrome causes arrhythmias and atypical autism
Children's researchers have found that calcium channel-blocking drugs may treat a rare genetic syndrome that is often fatal by age 2. Named Timothy syndrome, it causes a variety of problems, including heart arrhythmias, webbed hands and feet and autism.

Led by Igor Splawski, PhD, in the Cardiovascular Research Division, and Howard Hughes Medical Institute investigator Mark Keating, MD, the researchers found 17 affected children and showed that the syndrome arises from a single, subtle gene mutation. The mutation affects a calcium channel found in cells throughout the body, so many organ systems are affected.

In future studies, Splawski and Keating will investigate whether calcium channel blockers can ameliorate Timothy syndrome, and whether this type of calcium channel is involved in other forms of autism. They will also continue looking for other genes and calcium channels involved in arrhythmias. Their report appears in the October 1 issue of Cell.

Beaker bytes is a monthly column in Children's News. If you have received a grant, launched a new study or have a paper accepted for publication, contact Nancy Fliesler at ext. 5-2426 or via email at nancy.fliesler@childrens.harvard.edu.