Kortlynn Johnson

What is Gene Therapy?A technique for correcting defective genes

responsible for disease development1

Correcting Faulty Genes

1. A normal gene may be inserted into a nonspecific location within the genome to replace a nonfunctional gene.

*Most common*2. An abnormal gene could be swapped for a

normal gene through homologous recombination.

3. The abnormal gene could be repaired through selective reverse mutation, which returns the gene to its normal function.

4. The regulation (the degree to which a gene is turned on or off) of a particular gene could be altered.

Doctors may use 1 of these approaches1:

How Does Gene Therapy Work?1In most gene therapy studies, a "normal"

gene is inserted into the genome to replace an "abnormal," disease-causing gene. Carrier molecule VectorMost common carrier Virus

A Vector in ACTION!!!2

Types of Vectors1Retroviruses

Create double-stranded DNA copies of their RNA genomes

These copies of its genome can be integrated into the chromosomes of host cells

Adenoviruses Have double-stranded DNA genomes that

cause respiratory, intestinal, and eye infections in humans.

Types of Vectors1Adeno-associated viruses

Small, single-stranded DNA viruses that can insert their genetic material at a specific site on chromosome 19

Herpes simplex viruses Double-stranded DNA viruses that infect a

particular cell type – neurons

Non-Viral Approaches1Direct introduction of therapeutic DNA into

target cellsSimplest method This approach is limited in its application

because it can be used only with certain tissues and requires large amounts of DNA.

Non-Viral Approaches1Another nonviral approach involves the

creation of an artificial lipid sphere with an aqueous core. This liposome, which carries the therapeutic

DNA, is capable of passing the DNA through the target cell's membrane.

Non-Viral Approach (Liposome Method)3

Applications of Gene Therapy1Current

Researchers also are experimenting with introducing a 47th (artificial human) chromosome into target cells.

This chromosome would exist autonomously alongside the standard 46 --not affecting their workings or causing any mutations.

Applications of Gene Therapy1It would be a large vector 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 potential method is the difficulty in delivering such a large molecule to

the nucleus of a target cell.**

Gene Therapy: Going Global1The School of Pharmacy in London is testing a

treatment in mice, which delivers genes wrapped in nanoparticles to cancer cells to target and destroy hard-to-reach cancer cells. (March 2009)

UK researchers from the UCL Institute of Ophthalmology and Moorfields Eye Hospital NIHR Biomedical Research Centre announced results from the world’s first clinical trial to test a revolutionary gene therapy treatment for a type of inherited blindness. The results show that the experimental treatment is safe and can improve sight. (April 2008)

Gene Therapy: Going Global1In France, gene therapy performed on

children suffering from Severe Combined Immunodeficiency was halted because one of the patients developed leukemia as a direct consequence of the treatment. (October 2002)4

Gene Therapy: Going Global1China’s first gene therapy was just recently

approved in 2003.China's medicines authority approved the

cancer therapy after it achieved promising results in a clinical trial.

Setbacks for Advancement…1The Food and Drug Administration (FDA) has

not yet approved any human gene therapy product for sale.

Setbacks for Advancement…1In 1999, gene therapy suffered a major

setback with the death of 18-year-old Jesse Gelsinger. Jesse was participating in a gene therapy trial for ornithine transcarboxylase deficiency (OTCD).

He died from multiple organ failures 4 days after starting the treatment. His death is believed to have been triggered by a severe immune response to the adenovirus carrier.

Some Ethical Questions to Consider about Gene Therapy1What is normal and what is a disability or

disorder, and who decides? Are disabilities diseases? Do they need to be

cured or prevented? Does searching for a cure demean the lives of

individuals presently affected by disabilities? Preliminary attempts at gene therapy are

exorbitantly expensive. Who will have access to these therapies? Who will pay for their use?

Pros and Cons of Gene Therapy5

Pros Cons Wipe out genetic disease

before it can begin and eliminate suffering for future applications

Good technique for diseases not researched yetPeople carry defected

genes and may be unawareGene therapy can eliminate

the consequences of carrying these genes

Putting human fate into our own hands

Creating a “superior race”“Playing God”

References1. http://www.ornl.gov/sci/techresources/

Human_Genome/medicine/genetherapy.shtml#whatis

2. http://www.unitedspinal.org/publications/action/wp-content/gene-therapy.jpg

3. http://www.nature.com/gt/journal/v13/n18/images/3302838f1.jpg

4. http://www.newscientist.com/article/dn2878-miracle-gene-therapy-trial-halted.html

5. http://www.ndsu.edu/pubweb/~mcclean/plsc431/students/eric.htm