6. Gene therapies

Gene therapy

Insertion, alteration, or removal of genes within an individual's cells and tissues in order to treat disease

Transformation

Transfer of naked DNA into bacteria.

Transfection

transfer of naked DNA into cells.

Infection

infect with a wild type virus

Transduction

A viral vector with foreign DNA introduced into another cell

Titer

way of expressing concentration of viral particles (Infectious Units per ml, IU/ml)

Ex vivo

Gene of interest transferred into patient’s cells. Ex vivo means "out of the living" in Latin.

In vivo

Viral vectors produced in the lab and injected into the target organ. In vivo means "within the living" in Latin.

Allogeneic ex vivo

from a donor

Autologous ex vivo

from the patient itself

Advantages of autologous

•Patient-specific

•No rejection by the immune system

•No risk for graft-vs-host disease

•Repeated doses possible

Challenges with autologous

•High costs for manufacturing and quality testing

•Starting material variability (donor variability)

Advantages of allogenic

•Larger-scale manufacturing possible

•Donor can be screened for desirable characteristics

•More reproducible manufacturing (less donor variability)

•Banking possible (immediate availability)

Challenges with allogenic

•Risk for graft-vs-host disease needs to be minimized through additional steps (cost increase)

•Risk of rapid rejection as cells are still recognized as foreign cells

ADA-SCID

• A rare disorder caused by the retrovirus inserted near a proto-oncogene promoter.

• Caused by a mutation that results in the absence of protein called adenosine deaminase (ADA), which is required for the production of lymphocytes.

• Children born with ADA-SCID do not develop a healthy immune system so cannot fight off everyday infections, which results in severe and life-threatening illness.