Gene Therapy

By: Chris Smith and Darran Prewitt

What is gene therapy? Why is it used?

• Gene therapy = Introduction of normal genes into cells that contain defective genes to reconstitute a missing protein product

• GT is used to correct a deficient phenotype so that sufficient amounts of a normal gene product are synthesized to improve a genetic disorder

How is Gene Therapy Carried Out?

• Modification of somatic cells by transferring desired gene sequences into the genome.

• Somatic cells necessary to ensure that inserted genes are not carried over to the next generation.

Forms Of Viral Transfers

• Retroviruses - A class of viruses that can create double-stranded DNA copies of their RNA genomes. These copies of its genome can be integrated into the chromosomes of host cells.

• Herpes simplex viruses - A class of double-stranded DNA viruses that infect a particular cell type, neurons.

Forms Of Viral Transfers(Cont.)• Adenoviruses - A class

of viruses with double-stranded DNA genomes that cause respiratory, intestinal, and eye infections in humans.

• Adeno-associated viruses - A class of small, single-stranded DNA viruses that can insert their genetic material at a specific site on chromosome 19.

Future Applications

• Researchers are also experimenting with introducing a 47th artificial chromosome. This chromosome would exist alongside the standard 46, not affecting their work or causing any mutations. It would be capable of carrying substantial amounts of genetic code, and scientists anticipate that, because of its construction and autonomy, the body's immune systems would not attack it. A problem with this method is the difficulty in delivering such a large molecule to the nucleus of a target cell.

Different Delivery Systems That are Available

• In vivo versus ex vivo• In vivo = delivery of genes takes

place in the body• Ex vivo = delivery takes place out of

the body, and then cells are placed back into the body

• Problem: Replication defective viruses adversely affect the virus’ normal ability to spread genes in the body• Reliant on diffusion and spread• Hampered by small intercellular spaces

for transport• Restricted by viral-binding ligands on cell

surface therefore cannot advance far.

• More than 5000 patients have been treated in last ~12 years worldwide

References

• http://www.ornl.gov/sci/techresources/Human_Genome/medicine/genetherapy.shtml