By Dr Ananya Mandal, MD
The concept of gene therapy arose during the 1960s and 1970s and is still in its infancy, meaning there is a paucity of reliable, long-term data on the safety and efficacy of this therapy.
In 1972, Theodore Friedmann and Richard Roblin published a paper in Science called "Gene therapy for human genetic disease?" which cited Stanfield Roger's proposal in 1970 that "good DNA" could be used to replace defective DNA in people with genetic disorders.
The first patient to be treated with gene therapy was a four year old girl treated at the NIH Clinical Center in 1990. She had a congenital disease called adenosine deaminase (ADA) deficiency which severely affects immunity and the ability to fight infections.
For the therapy, her white blood cells were taken from her and inserted with the correct genes for making ADA and then reinjected into her. This process was performed by Dr. W. French Anderson from the National Heart, Lung and Blood Institute.
In 1985, Anderson and colleague Michael Blease started working together to demonstrate how cells from people with ADA deficiency could be modified in tissue culture. They used a retrovirus as a vector to carry the correct ADA gene into the cells.
In 1986, they tried transferring the correct genes into the bone marrow of animals, but in 1988, found that transferring them to white blood cells was much more successful, with a dramatic increase in the amount of the correct genes being taken up by cells.
In 1989, the researchers teamed up with Dr. Steven Rosenberg to test how safe and effective the gene therapy would be in cancer patients. The team cultured tumor infiltration lymphocytes cells (TIL cells) from people with malignant melanoma.
A viral vector was made that would carry a DNA marker into those cells and these marked cells allowed the researchers to see which TIL cells were the most effective and also confirmed that the engineered virus was safe for use in humans.
In 1990, the four-year old girl and another nine-year old girl with ADA deficiency were infused with their own corrected cells over two years and in 1993, the team used the gene therapy to treat newborn infants with ADA deficiency. The corrected ADA genes were transferred to immature blood cells obtained from the babies' umbilical cords.
Reviewed by Sally Robertson, BSc
Last Updated: Jan 14, 2014