Gene Therapy - The Future Is Here!

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Medical Author: Frederick Hecht, MD, FAAP, FACMG

Gene therapy is the treatment of disease by replacing, altering, or supplementing a gene that is absent or abnormal and whose absence or abnormality is responsible for the disease. Gene therapy may use the genetic material, DNA, itself as the means of treatment.

DNA or deoxyribonucleic acid is the very long molecule that encodes the genetic information. A gene is a stretch of DNA required to make a functional product such as part or all of a protein. People have about 100,000 to 150,000 genes. During gene therapy, DNA that codes for specific genes is delivered to individual cells in the body.

Most, if not all, diseases have a genetic factor. The genetic factor can be wholly or partially responsible for the disease. For example, in disorders such as cystic fibrosis, hemophilia, and muscular dystrophy, changes in a gene directly result in the condition. In other conditions such as high cholesterol and high blood pressure, genetic and environmental factors interact to cause disease. Disorders associated with aging often involve the loss of gene activity in specific types of cells. Even infections can be related to genes. In fact, they have two sets of genetic determinants: the genes of the infective agent and the genes of the person with the infection.

Uses of gene therapy

Gene therapy is being used in many ways. For example, to:

  • Replace missing or defective genes;
  • Deliver genes that speed the destruction of cancer cells;
  • Supply genes that cause cancer cells to revert back to normal cells;
  • Deliver bacterial or viral genes as a form of vaccination;
  • Provide genes that promote or impede the growth of new tissue; and;
  • Deliver genes that stimulate the healing of damaged tissue.

A large variety of genes are now being tested for use in gene therapy. Examples include: a gene for the treatment of cystic fibrosis (a gene called CFTR that regulates chloride); genes for factors VIII and IX, deficiency of which is responsible for classic hemophilia (hemophilia A) and another form of hemophilia (hemophilia B), respectively; genes called E1A and P53 that cause cancer cells to undergo cell death or revert to normal; AC6 gene which increases the ability of the heart to contract and may help in heart failure; and VEGF, a gene that induces the growth of new blood vessels (angiogenesis) of use in blood vessel disease.

A short synthetic piece of DNA (called an oligonucleotide) is being used by researchers to "pre-treat" veins used as grafts for heart bypass surgery. The piece of DNA seems to switch off certain genes in the grafted veins to prevent their cells from dividing and thereby prevent atherosclerosis.

Delivery of genes into cells

Gene delivery can be used in cells that have been removed from the body (ex vivo gene therapy) or in cells that are still in the body (in vivo gene therapy). Genes can be delivered into cells in different ways. The selection of a gene delivery system depends on the target cell, the duration of gene expression required for therapeutic effect, and the size of the piece of DNA to be used in the gene therapy.

Genes can be carried into cells by viruses. Viral vectors or carriers take advantage of the natural ability of a virus to enter a cell and deliver genetic material to the nucleus of the cell that contains its DNA. In developing virus carriers, the DNA coding for some or all of the normal genes of the virus to be used as a carrier are removed and replaced with a treatment gene. Most of these virus carriers are engineered so that they are able to enter cells, but they cannot reproduce themselves and so are innocuous.

Genes can also be delivered within tiny synthetic "envelopes" of fat molecules. Cell membranes contain a very high concentration of fat molecules. The fat molecule "envelope" can carry the therapeutic gene into the cell by being admitted through the cell membrane as if it were one of its own molecules.

Genes can also gain entrance into cells when an electrical charge is applied to the cell to create tiny openings in the membrane that surrounds a cells. This technique is called electroporation.

A "bionic chip"

A new "bionic chip" has been developed to help gene therapists using electroporation to slip fragments of DNA into cells. Electroporation was originally a hit-or-miss technique because there was no way to determine how much of an electrical jolt it took to open the cell membrane.

The "bionic chip" solves this problem. It contains a single living cell embedded in a tiny silicon circuit. The cell acts as a diode, or electrical gate. When it is hit with just the right charge, the cell membrane opens, allowing the electricity to pass from the top to the bottom of the bionic chip. By recording what voltage caused this phenomenon to occur, it is now posssible to determine precisely how much electricity it takes to pry open different types of cells.

Route of administration of gene therapy

The choice of route for gene therapy depends on the tissue to be treated and the mechanism by which the therapeutic gene exerts its effect. Gene therapy for cystic fibrosis, a disease which effects cells within the lung and airway, may be inhaled. Most genes designed to treat cancer are injected directly into the tumor. Proteins such as factor VIII or IX for hemophilia are also being introduced directly into target tissue (the liver).

The potential power of gene therapy

Most gene therapy for diseases such as cystic fibrosis and hemophilia has been designed only to ease, not to cure, the disease. However, the delivery of functional copies of genes provides a potential method to correct a disease at its most basic level.

Gene therapy also holds the potential to provide "patient- friendly" treatment regimens for a variety of diseases. Today, many patients with hemophilia and diabetes must have repeated injections in order to manage their disease because proteins exist in the blood stream for a limited period of time before they are degraded or eliminated. Since DNA is more stable and functions inside the cell, the delivery of genes may result in longer-term expression of the necessary proteins.


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Because of its accuracy, gene therapy has the potential to eliminate cancer cells without damaging normal, healthy tissue. Furthermore, cancer gene therapies may provide alternatives when a disease does not respond to other older treatments.

The potential of gene therapy is great but, compared to its promise, the results to date are still quite limited. However, the benefits of gene therapy are believed to be on the near horizon. Gene therapy is one of the hottest areas of medical research today. (And gene therapy companies have been among the hottest in the stock market.)

The remarkable advances in genetics, including the human genome project, have opened new doors for the exploration of gene therapy. New technologies are needed to speed the progress of gene therapy. As these new technologies such as the "bionic chip" arrive, we believe that, without a doubt, gene therapy will play an increasingly important and prominent part in medicine in the decades to come.

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