What  is Gene Therapy?

Recent advances in understanding and manipulating genes -- the biological units of heredity -- have set the stage for scientists to alter patients' genetic material to fight or prevent disease. One major goal of gene therapy is to supply cells with healthy copies of missing or flawed genes. This approach is revolutionary: Instead of giving a patient a drug to treat or control the symptoms of a genetic disorder, physicians attempt to correct the basic problem by altering the genetic makeup of some of the patient's cells.

Hundreds of major health problems are influenced by gene functions. In the future, gene therapy could be used to treat many of these conditions. Theoretically, it could also be used to alter germ cells (egg or sperm) in order to prevent a genetic defect from being transmitted to future generations . However, the possibility of germ-line gene therapy is beset by difficult ethical and social questions as well as technical obstacles.

Gene therapy could also be used as a drug delivery system. To accomplish this, a gene that produces a useful product would be inserted into the DNA of the patient's cells. For example, during blood vessel surgery, a gene that makes an anticlotting factor could be inserted into the DNA of cells lining blood vessels to help prevent dangerous blood clots from forming. Many other conditions might also lend themselves to treatment using this general approach.

As medicine operates increasingly on the molecular level, using gene therapy for drug delivery could save much effort and expense. It could shortcut the lengthy and complicated process of collecting large amounts of a gene's protein product, purifying the product, formulating it as a drug, and administering it to the patient.

However, gene therapy is still extremely new and highly experimental. The number of approved trials is small, and relatively few patients have been treated to date.

Basic Steps involved in current Gene Therapy Experiments

In some current experiments, cells from the blood or bone marrow are removed from the patient and grown in the laboratory under conditions that encourage them to multiply. Then the desired gene is inserted into the cells with the help of a disabled virus, and the successfully altered cells are selected out, encouraged to multiply, and returned to the patient's body. In other cases, liposomes (fatty particles) or disabled viruses may be used to deliver the gene directly to cells within the patient's body.

Basic Requirements for Gene Therapy

Potential of gene therapy.
Gene therapy offers a new treatment paradigm for curing human disease. Rather than altering the disease phenotype by using agents which interact with gene products, or are themselves gene products, gene therapy can theoretically modify specific genes resulting in disease cure following a single administration. Initially gene therapy was envisioned for the treatment of genetic disorders, but is currently being studied in a wide range of diseases, including cancer, peripheral vascular disease, arthritis, neurodegenerative disorders and other acquired diseases.

Gene identification and cloning.
 
Even though the range of gene therapy strategies is quite diverse, certain key elements are required for a successful gene therapy strategy. The most elementary of these is that the relevant gene must be identified and cloned. Upon completion of the Human Genome Project, gene availability will be unlimited, but until then the starting point for any gene therapy strategy remains gene identification and cloning for relevant genes related to the disease.

Gene transfer and expression.
 
Once the gene has been identified and cloned, the next consideration must be expression. Questions pertaining to the efficiency of gene transfer and gene expression remain at the forefront of gene therapy research. Currently much debate in the field of gene therapy revolves around the transfer of desired genes to appropriate cells, and then obtaining sufficient levels of expression for disease treatment. Hopefully, future research on gene transfer and tissue-specific gene expression will resolve these issues in the majority of gene therapy protocols. Other important considerations for a gene therapy strategy include: a sufficient understanding of the pathogenesis of the targeted disorder, potential side effects of the gene therapy treatment, and understanding of the target cells to receive the gene therapy.

Terminology

Like most fields, gene therapy has unique terminology. The list provided below will clarify the meaning of some of the most common terms.

Ex vivo  gene transfer:
transfer of genetic material to cells located outside the host. Following transfer of the genetic material, the cells are then implanted back into the host. This term has also been called the indirect method of gene transfer.
In vivo  gene transfer:
transfer of genetic material to cells located within the host. This has also been termed the direct method of gene transfer.
Gene therapy:
the transfer of selected genes into a host with the hope of ameliorating or curing a disease state.
Cell therapy (genome therapy):
the transfer of entire cells, that have not been genetically modified, into a host with the hope that the transferred cells will engraft into and improve host function.
Somatic gene transfer:
transfer of genes to non-germline tissues in the hope of correcting the disease state of a patient.
Germline gene:
transfer of genes to germline (eggs or sperm) tissues in the hope of altering the genome of future generations.
Transgene:
the selected gene tested in a gene transfer experiment. For example, if you wished to treat a patient for phenylketonuria, you might plan to transfer a corrected version of the phenylalanine hydroxylase gene into the liver cells. In this example, the corrected version of the phenylalanine hydroxylase gene would be the transgene.
Reporter gene:
genes which are used to test the efficiency of gene transfer. Examples include genes encoding luceriferase, -galactosidase, and chloramphenicol acetyltransferase.
Gene transfer vector:
the mechanism by which the gene is transferred into a cell.
Transfer efficiency:
the percentage of cells which are expressing the desired transgene.