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GENE THERAPY BASICS

Gene therapy studies hold great hope for treating disease and for enhancing lives. In the long run, it may someday cure cancer and enable the heart to grow new vessels to replace clogged ones.

Several thousand genes live in every human cell, each one having a specific function. When one is missing or damaged, it can disrupt the natural processes of the body and cause disease. Scientists are using gene therapy techniques to correct defective genes responsible for disease development. The objective is to treat diseases by delivering functional genes into the body by either replacing missing genes or providing copies of functioning genes to replace abnormal disease-causing ones.

Various classes of agents, or vectors, such as modified viruses and non-viral systems can be used to delivery functional genes into a patient for disease treatment. Viruses have evolved specialized mechanisms to efficiently transport their own DNA into the host cell, making them a powerful tool for engineering vector systems for gene delivery. Scientists at LGTRC are interested in the targeted delivery of these vectors and their associated functional genes to the proper site within the host and the proper regulation of their expression. Scientists are also exploring the potential of adult stem cells as vehicle for gene delivery.

Almost all diseases have a genetic component. Gene therapy is a technique for preventing or curing disease by correcting the defective genes responsible for the disease’s development.

Gene therapy's ultimate goal is to administer a treatment that results in a lifetime correction of a defect and absolutely cures a disease.

You look a little like your mother and a little like your father because of the genes they gave to you. Genes, composed of deoxyribonucleic acid—DNA, carry the information needed to make proteins. Proteins are the building blocks of our body and include many substances such as enzymes, hormones, and antibodies.

The body buries genes deep in the heart of every cell, the nucleus, and organizes them in the chromosomes that hold the DNA. But when your DNA is damaged, it no longer makes all the needed proteins and disease can result.

How does Gene Therapy work?

To reverse disease caused by genetic damage, researchers isolate normal DNA and package it into a vector, a molecular delivery truck usually made from a disabled virus. Doctors then infect a target cell —usually from a tissue affected by the illness, such as liver or lung cells— with the vector. The vector unloads its DNA cargo, which then begins producing the missing protein and restores the cell to normal.


Currently, the most common vector is a virus that has been genetically altered to carry normal human DNA. Viruses cause disease by encapsulating and delivering their genes to human cells. Scientists want to take advantage of this capability by replacing the virus’s disease-causing genes with new therapeutic genes. The virus delivers the gene but cannot replicate or cause an infection.

There are several different things that can be done to "program" a virus. It can be designed so that it is only active in a specific type of cell or tissue in the body. It can be designed to enter only a specific cell in the body, or drugs can be used to turn the gene on and off when you want it on or off. It can be used in several ways depending on the disease situation. Where a disease causing gene abnormality exists, the virus can be constructed with a repaired version of the gene. The virus then delivers a correct copy of the gene to fix the broken gene (mutated). In the case of cancer, scientists send new genetic instructions to the cancer cells and cause them to self destruct.

Why use gene therapy instead of drugs?

Drugs work from the outside in, and must be continuously re-administered if the disease is chronic. Gene therapy works from the inside, and should keep working indefinitely. It holds the potential to provide patient-friendly treatment for a variety of diseases.

About 4,000 diseases have been traced to genetic disorders. Gene therapy is likely to be most successful with diseases caused by single gene defects. A key struggle for researchers is finding the right gene to address the disease in question, and making sure that gene is delivered to the right place in the body.

Diseases that may benefit from Gene Therapy

Developmental and metabolic disorders: Cystic fibrosis, retinoblastoma

Neurological disorders: Parkinson's, Huntington's chorea, Alzheimers

Infectious disease: AIDS, Malaria, other viral infections (including human papilloma virus)

Immune-mediated diseases and immunodeficiency: Severe Combined Immunodeficiency Disease, Rheumatoid Arthritis, Type 1 Diabetes and Multiplesclerosis

Acquired disorders: Heart disease, Cancer (including brain cancer)

What are Clinical Trials?

Clinical trials are research studies that determine how a new drug or therapy works on humans. Clinical trials are closely monitored by the Food and Drug Administration and are usually conducted in four phases:

Phase I Trials: Tests the safety, dosage, and response to the therapy on a small group of people, sometimes as few as half a dozen.

Phase II Trials: The basic effectiveness of the potential therapy is tested on a small population of patients affected with the disease or condition that requires treatment.

Phase III Trials: The results for people undergoing the new treatment are compared to results for people using standard treatments to determine survival rates and side effects. Phase III trails may include anywhere from 50 to 5,000 patients at many clinics, hospitals, and doctor's offices.

What are some recent developments in gene therapy research?

While most of gene therapy research is focused on cancer treatment, some progress is being made in other areas.

University of California, Los Angeles, research team gets genes into the brain using liposomes coated in a polymer call polyethylene glycol (PEG). The transfer of genes into the brain is a significant achievement because viral vectors are too big to get across the "blood-brain barrier." This method has potential for treating Parkinson's disease.

Researchers at Children's Hospital of Philadelphia, Stanford University and Avigen, Inc., a biotech company in Alameda, Calif., have reported promising results in hemophilia B patients. The team packaged a gene for Factor IX, a blood clotting protein, in a defective adeno-associated virus (AAV). They then used the AAV to insert the gene into patients who suffered abnormal blood clotting because they lack Factor IX.

Tulane University Health Sciences Center researchers, in New Orleans, have developed new procedures that make it possible to grow extremely large numbers of cells from a small sample of cells taken from a patient's bone marrow. The ability to rapidly grow cells makes it possible to gene engineer the cells with simple techniques that do not involve the use of a virus.

The researchers are using the technique to treat mice and rats suffering from the equivalent of brittle bone disease in humans. The aim of the experiment is to determine if the cells can travel to the site of a bone fracture and strengthen the bone to prevent further injuries. It holds great promise for treating human bone diseases such as osteoporosis.

In other experiements the Tulane Researchers are pursuing their discovery that adult stem cells can differentiate into cells that make up the brain. If the cells can replace the missing protein and reverse the degeneration of the brain, diseases like parkinson's and alzheimer's may be controlled or cured.