How gene therapy is emerging from its ‘dark age’

In a landmark 1972 paper1, physician Theodore Friedmann and biochemist Richard Roblin foresaw a future in which DNA could be manipulated to help treat human genetic diseases. But they cautioned that it should remain off-limits until the field gained a firmer grasp of genetic processes in cells, their relationship to disease and the potential side effects of treatments.

Over the following years, scientists began to remove these obstacles, and in 1990 achieved a major breakthrough when a four-year-old girl with a form of severe combined immunodeficiency disease was successfully treated in a clinical trial2. This ushered in a decade of high hopes and bold promises.
But the afterglow of that early achievement proved short-lived, as a labyrinth of technical challenges emerged. A common gene-therapy approach involves delivering a healthy gene to cells that have only defective copies in their genetic libraries. Once inside, the therapeutic gene instructs the cells to manufacture functional proteins instead of faulty ones. One difficulty has been making sure a treatment gene zeroes in on the correct cells in the right tissue, and is shuttled into...