1.

Retroviruses were discovered in 1910, when Peyton Rous induced malignancy in chickens by the
injection of cell-free filtrates from muscle tumor, we have gained much insight into their
mechanism of action. Three main classes of recombinant retroviruses are used as tools in gene
delivery: γ-retroviruses, lentiviruses, and spumaviruses. Despite their negative press, exogenous
retroviruses have been used in many biological studies and facilitated the discovery of proto-
oncogenes, the manipulation and investigation of intracellular pathways, and successful ex
vivo treatment of persons with hemophilia and SCID.
2. Adenoviridae were initially isolated by Wallace Rowe in 1953 from adenoid explants as the
“virus of the common cold”. They have since become attractive tools for gene therapy, given
that their infection is generally self-limiting and non-fatal. Adenoviruses are the largest non-
enveloped virus and contain linear, double-stranded DNA. Over 50 serotypes have been
identified, but the most common in nature and in adenoviral gene therapy are group C human
serotypes 2 and 5. The icosahedral adenoviral capsid is made up of hexon and penton proteins,
knobbed fibers, and stabilizing minor cement proteins. 
3. 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.
4. 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.
5.

References

Gene Therapy - PMC (nih.gov)

Gene Therapy History (news-medical.net)