Gene Therapy

Visualize   By Tracy Staedter   May 2002

How viruses deliver healing DNA to malfunctioning cells.

Cells are lifeís biological factories, churning out proteins, the building blocks of the human body. DNA is the blueprint that directs their operation. If a segment of DNA, or gene, is mutated, the cell that houses it could produce defective proteinsóor none at all. In some cases, such malfunctions cause disease, such as muscular dystrophy or hemophilia. Gene therapy attempts to deliver a corrected version of the cellís DNA to its nucleus, restoring its normal protein-producing function.

The most successful vehicle so far is adeno-associated virus, which does not cause any known diseases or trigger immune responses such as inflammation. In the lab, most of the virusís own DNA is removed and replaced with therapeutic DNA. Then itís injected into the patientís tissue, where it does what it does best: infect cells. At the cell, proteins on the virus match up with receptor proteins on the cellís surface. The cell then closes around the virus, seals it within a separate membrane and absorbs it. Inside the cellís cytoplasm, the membrane breaks down and the virus heads for tiny pores in the nucleusís membrane. Biologists think the virus either slips through a pore or squirts the therapeutic gene inside. Once ensconced in the nucleus, the correct DNA sends genetic information called mRNA back out into the cytoplasm, where a ribosome uses it to manufacture the correct protein.

Human gene therapy experiments began in 1990, but researchers met with limited success and in some cases were banned from testing altogether. Itís only in the last couple of years that gene therapy has shown renewed promise. Several human studies, including ones under way at the University of Pennsylvania and at Alameda, CA-based Avigen, are indicating the procedureís success in combating hemophilia and may pave the way for its use against ailments including Parkinsonís disease and cystic fibrosis. If perfected, gene therapy should cure the diseases that doctors today can only treat.

Tracy Staedter is the managing editor at Technology Review.