Gene therapy is a technique where a gene is inserted into a person’s cells to prevent or treat a serious disease. The added gene may be a healthy version of the gene that is mutated in the patient, or it could be a different gene that inactivates or compensates for the patient’s disease-causing gene. For example, in patients with severe combined immunodeficiency (SCID) due to a mutation in the gene for the enzyme adenosine deaminase, a functioning version of the gene can be inserted. The patient’s cells can then make the enzyme, curing this potentially deadly disease in some cases.

Gene Insertion

Genes can be introduced into a patient’s cells in two main ways: in vivo—directly into a person through injection into specific tissues or into the bloodstream; and ex vivo—into cells that have been removed from the patient, which are transplanted back after the gene is inserted.

The gene is usually inserted into a vector—often a virus that has been modified to not cause disease—to get the gene into the patient’s cells and delivered to the nucleus. In some cases—for instance, when retroviral vectors are used—the gene is randomly inserted into the person’s genome, leading to stable expression of the inserted gene. In others—such as when adenoviral vectors are used—the gene does not integrate into the host’s genome and is only transiently expressed. The vector is also engineered to contain a promoter region so that the new gene can be transcribed into messenger RNA (mRNA). Then, using the cell’s own machinery, the mRNA is translated into protein. The protein product—such as adenosine deaminase—provides the treatment for the disease.

Clinical Trials

Gene therapy is still in the early stages and carries significant risks, in part because the integration and activity of the inserted genes cannot be fully controlled. For example, in some early trials of gene therapy for another form of SCID, some patients developed cancer, and the trials were halted. However, the technology is continually improving, and for serious diseases with no other effective treatment, the benefits can outweigh the risks. Besides SCID, other diseases where gene therapy has been successful include a type of inherited blindness and treatment-resistant B-cell leukemia.