Gene Therapy Health Article

Definition

Gene therapy is a rapidly growing field of medicine in which genes are introduced into the body to treat diseases. Genomics is the DNA which is found in an organism's total set of genes and is passed on to the offspring as information necessary for survival. Genetics is the study of the patterns of inheritance of specific traits. Genes control heredity and provide the basic biological code for determining a cell's specific functions. Gene therapy seeks to provide genes that correct or supplant the disease-controlling functions of cells that are not performing in a normal manner.

Somatic gene therapy introduces therapeutic genes at the tissue or cellular level to treat a specific individual. Germ-line gene therapy inserts genes into reproductive cells or possibly into embryos to correct genetic abnormalities that could be passed on to future generations. Initially conceived as an approach for treating inherited diseases such as cystic fibrosis and Huntington's disease, the scope of potential gene therapies has grown to include treatments for cancer, arthritis, and infectious diseases.

The history of gene therapy

In the early 1970s, scientists proposed "gene surgery" for treating inherited diseases caused by abnormally functioning genes. The idea was to take out the disease-causing gene and surgically implant a gene that functioned correctly. Although sound in theory, and after some advances in science, this technique has not yet been successful.

However, in 1983, a group of scientists from Baylor College of Medicine in Houston, Texas, proposed that gene therapy could one day be a viable approach for treating Lesch-Nyhan disease, a rare neurological disorder. The scientists conducted experiments in which an enzyme-producing gene (a specific type of protein) for correcting the disease was injected into a group of cells for replication. The scientists theorized the cells could then be injected into people with Lesch-Nyhan disease, thus correcting the genetic abnormality that caused the disease.

As the science of genetics advanced throughout the 1980s, gene therapy grew in the estimation of medical scientists as a promising approach to treatments for specific diseases. One of the major reasons for the growth of gene therapy was the increasing body of knowledge available to assist in identifying the specific genetic malfunctions that caused inherited diseases. Interest grew as further studies of DNA and chromosomes (where genes reside) showed that specific genetic abnormalities in one or more genes occurred in successive generations of certain family members who experienced diseases like intestinal cancer, manic-depression (bipolar disorder), Alzheimer's disease, heart disease, diabetes, and many more. Although genes may not be the only cause of the disease in all cases, they may make certain individuals more susceptible to developing a particular condition due to such environmental influences as smoking, pollution, and stress. In fact, some scientists theorize that all diseases may have a genetic component.

The biological basis of gene therapy

Gene therapy has grown out of the science of genetics or how heredity functions. Scientists know that life begins in a cell, the basic building block of all multicellular organisms. Humans, for instance, are made up of trillions of cells, each performing a specific function. Within each cell's nucleus (the center part of a cell that regulates its chemical functions) are pairs of chromosomes. These threadlike structures are made up of deoxyribonucleic acid (DNA), which carries the blueprint of life in the form of codes, or genes, that determine dominant or recessive inherited characteristics.

A DNA molecule looks like two ladders with one of the sides taken off both and then twisted around each other—a formation known as the double helix. The rungs of these ladders meet (resulting in a spiral staircase-like structure) and are called base pairs. Base pairs are made up of nitrogen-containing molecules and arranged in specific sequences. Millions of these base pairs, or sequences, constitute a single gene, specifically defined as a segment of the chromosome and DNA that contains certain hereditary information. The gene, or combination of genes formed by these base pairs, ultimately directs an organism's growth and characteristics through the production of certain chemicals—primarily proteins that carry out most of the body's chemical functions and biological reactions.

Scientists have long known that alterations in the genes present within cells may cause such inherited diseases as cystic fibrosis, sickle-cell disease, and hemophilia. Similarly, errors in entire chromosomes may cause such conditions as Down syndrome or Turner syndrome. As the study of genetics advanced, however, scientists learned that altered genetic sequences may also make people more susceptible to such diseases as atherosclerosis, cancer, and schizophrenia. These diseases have a genetic component, but are also influenced by such environmental factors as diet and lifestyle. The objective of gene therapy is to treat diseases by introducing functional genes into the body to alter the cells involved in the disease process, either by replacing missing genes or by providing copies of functioning genes to replace nonfunctioning ones. The inserted genes may be naturally occurring genes that produce the desired effect or may be engineered (or altered) genes.

Scientists have known how to manipulate a gene's structure in the laboratory since the early 1970s through a process called gene splicing. The process involves removing a fragment of DNA containing a specific desired genetic sequence and then inserting it into the DNA of another gene. The resultant product is called recombinant DNA, and the process is called genetic engineering. This technique is used in preparing some new therapies (monoclonal antibodies, blood component replacements for hemophilia, antiinflammatory therapy for collagen diseases).

There are two types of gene therapy. Germ-line gene therapy introduces genes into reproductive cells (sperm and eggs) to participate in germination. Some scientists hope that it may eventually be possible to insert genes into embryos in hopes of correcting genetic abnormalities that can then be passed on to future generations. Most of the current work in applied gene therapy, however, has been in the realm of somatic therapy. In this type of gene therapy, therapeutic genes are inserted into tissue or cells to produce a naturally occurring protein or substance that is lacking or not functioning correctly in an individual.