Gene Therapy

Gene therapy is a medical approach that treats or prevents disease by changing the genes in a patient's cells, usually by adding a working copy of a gene or by editing a faulty one. Most approved treatments so far target rare inherited diseases.

Most therapies use a modified virus as a vector, because viruses are efficient at entering cells. Adeno-associated viruses are used to deliver genes that stay outside the chromosomes in non-dividing cells, while lentiviruses, which are retroviruses, integrate into the DNA of dividing cells such as blood stem cells, as discussed in viral vector engineering. In ex vivo treatment, cells are modified in the laboratory and returned to the patient, whereas in vivo treatment delivers the vector directly.

The first clinical trial in 1990 treated a girl with ADA deficiency, a severe immune disorder. A trial death in 1999 and cases of leukemia in early retroviral trials slowed the field. Approvals followed: Luxturna in 2017 for an inherited form of blindness, Zolgensma in 2019 for spinal muscular atrophy, and Casgevy in 2023, the first therapy made with CRISPR gene editing, for sickle cell disease.

Some treatments cost more than a million dollars per patient, and immune responses to the vector can limit repeat dosing. Gene-modified immune cells are also used against cancer, as in CAR-T therapy. Changes in germ cells, which would be inherited, are widely prohibited. The field draws on genetic engineering and on knowledge of diseases such as cystic fibrosis.

• CRISPR and Gene Editing — a newer tool for therapy
• Viral Vector Engineering — how the vectors are built
• Sickle Cell Disease — a disease treated by gene therapy