The once and future gene therapy

Abstract

Gene therapy is at an inflection point. Recent successes in genetic medicine have paved the path for a broader second wave of therapies and laid the foundation for next-generation technologies. This comment summarizes recent advances and expectations for the near future.

Fig. 1. Timeline depicting milestones (in colored arrows) towards gene therapies for common disease.

Approved treatments and year of their approval as well as investigational therapies (in dashed boxes) are shown below each milestone. Further exploration of alternative therapeutic approaches and fundamental scientific questions is still needed to accomplish later milestones (shown in bullets).

Fig. 2. Schematic of ex vivo and in vivo strategies (shown in blue boxes) for treating genetic diseases.

For ex vivo approaches (left panel), autologous cells can be isolated directly from the patient and genetically modified to elicit a therapeutic effect, while allogeneic cells can be produced and readily available “off the shelf.” In vivo strategies require targeting of specific cells in order to overexpress a therapeutic gene or correct pathological mechanisms to allow functional gene expression (dashed arrows).