Gene Therapy

Developers

S. Rogers, T. Friedmann, R. Roblin, A. Bartke, H. M. Brown-Borg, L. P. Guarente etc.

Description of the technology

The objective of gene therapy is to treat, cure or ultimately prevent disease by changing the expression of a person’s genes. Gene therapy can be targeted to somatic (body) or germ (egg and sperm) cells. In somatic gene therapy the recipient’s genome is changed, but the change is not passed along to the next generation. In germline gene therapy, the parent’s egg or sperm cells are changed with the goal of passing on the changes to their offspring. Germline gene therapy is not being actively investigated, at least in larger animals and humans, although discussion is intense over its value and desirability.

Practical application

Gene therapy is still in its infancy. It has the potential to become an important treatment regimen by countering genetic diseases with short life expectancy such as cystic fibrosis. This technology allows to eliminate diseased genes or rescue their normal functions. Furthermore, the transfer procedure of genetic materials allows the addition of new functions to cells such as the production of immune system mediator proteins.

Today, new hopes for controlled and specific genetic manipulation have arisen with the potential use of human embryonic stem cells. The human embryonic stem cells could be genetically manipulated to introduce the therapeutic gene. This gene may either be active or awaiting later activation once the modified embryonic stem cell has differentiated into the desired cell type.

It should be noted that some warning cases involving gene therapy show a high risk of genetic manipulation or epigenetic consequences.

Variants of technology

In case of gene therapy the therapeutic gene should targets only those cells affected by the disorder. How can it be reached? One solution is through the use of a vector. A vector is simply a «transporter» for the genetic material. Vectors must be administered to target specific cell types. There are three principal ways in which vectors can be administered to carry new genes into target cells:

А. Ex vivo somatic gene therapy.

The target cells are removed from the body, cultured in the laboratory with a vector, and re-inserted into the body.

Use

This technology is usually carried out using blood cells because they are the easiest to remove and return.

B. In situ somatic gene therapy.

Description

A vector is placed directly into the affected tissue.

Use

This technology is being developed for the treatment of cystic fibrosis (by direct infusion of the vector into the bronchi of the lungs), to destroy tumours (e.g.: brain cancer), and for the treatment of muscular dystrophy.

С. In vivo somatic gene therapy.

Description

The vector is injected into the bloodstream, and is able to find and insert new genes only into the cells for which it was specifically designed.

Use

Although there are presently no in vivo treatments available, a breakthrough in this area will make gene therapy a very attractive option for treatment. In this case the vector designed to treat our hypothetical patient could be injected into a blood vessel in her or his arm and would find its way to the affected brain cells!

Short historical facts

The concept of gene therapy arose during the 1960s and 1970s. Its development is connected with such names as Stanfield Rogers, Theodore Friedmann and Richard Roblin. The first gene therapy experiment approved by the US Food and Drug Administration (FDA) occurred in 1990, when Ashanti DeSilva was treated for ADA-SCID. By January 2014, some 2,000 clinical trials had been conducted or approved.

Laboratories

• Southern Illinois University (SIU) School of Medicine in Springfield, Illinois (USA)
• P. F. Glenn Laboratory for the Science of Aging at MIT, Department of Biology MIT, Cambridge, Massachusetts (USA)
• Genzyme, Cambridge, Massachusetts (USA)
• IUCF-HYU (Industry Cooperation Foundation Hanyang University), Seoul (South Korea)
• NewLink Genetics, Ames, Iowa (USA)

Links

Publications

• Brownborg, Holly M., et al. «Dwarf mice and the aging process." Nature 384.6604 (1996): 33–33.
• Guarente L., Kenyon C. Genetic pathways that regulate ageing in model organisms //Nature. — 2000. — Т. 408. — №. 6809. — С. 255–262.
• Chang P. L. Microcapsules as Bio‐organs for Somatic Gene Therapya //Annals of the New York Academy of Sciences. — 1997. — Т. 831. — №. 1. — С. 461–473.
• Westphal S. DNA nanoballs boost gene therapy //New Scientist. — 2002. — Т. 19. — С. 15–16.
• Li A. A. et al. Enhancement of myoblast microencapsulation for gene therapy //Journal of Biomedical Materials Research Part B: Applied Biomaterials. — 2006. — Т. 77. — №. 2. — С. 296–306.