Gene Therapy

Gene therapy has grown out of the field of molecular biology. Life begins with a single cell, the basic building block of all multicellular organisms. Humans, for instance, are made up of trillions of cells, that makeup tissues that form into organs. Each cell type can perform a specific function. Within the cells nucleus (the center part of a cell that regulates its chemical functions) are pairs of chromosomes. These threadlike structures are made up of DNA (deoxyribonucleic acid), which carries the blueprint of life in the form of codes, or genes, that are interspersed throughout the DNA sequence.

A DNA molecule looks like a twisted ladder. The rungs of these represent bonds between each letter of the DNA sequence called base pairs. Base pairs are made up of nitrogenous molecules. Thousands of these base pairs, or DNA sequences, can make up a single gene, specifically defined as a segment of the chromosome. The gene, or combination of genes formed by these base pairs ultimately direct an organisms growth and characteristics A scientist performing a microinjection of a corrective gene into a human T lymphocyte (a white blood cell). On screen can be seen the tip of the micropipette used for the injection (left) and the cell (right). The pipette is controlled by the joystick in the scientist's right hand. The procedure is being performed to treat a young girl whose immune system had collapsed because of her body's failure to produce an enzyme called adenosine deaminase (ADA) which controls the maturation of T cells. Lymphocytes collected from her are treated with the gene that expresses ADA and then reinjected into a vein. Results have been very good. Photograph by Philippe Plailly. National Audubon Society Collection/Photo Researchers, Inc. Reproduced by permission.

through the production of certain proteins, which are important for many biochemical functions.

Scientists have long known that defects in genes present within cells can cause inherited diseases such as cystic fibrosis, sickle-cell anemia, and hemophilia. Similarly, a gain or a loss of an entire chromosome can cause diseases such as Down Syndrome or Turners syndrome. As the study of genetics advanced, however, scientists learned that an altered genetic sequence can also make people more susceptible to develop diseases making these individuals predisposed to having atherosclerosis, cancer, or schizophrenia. These diseases have a genetic component, but are also influenced by environmental factors (like diet and lifestyle). The objective of gene therapy is to treat diseases by introducing corrected genes into the body to replace a missing or dysfunctional protein. The inserted genes can be naturally-occurring genes that produce the desired effect or may be genetically engineered (or altered) genes.

Scientists have known how to manipulate the sturcture of a gene in the laboratory since the early 1970's through a process called gene splicing. The process involves cutting a sequence of the genome with restriction enzymes, or proteins that act like molecular sicssors. The ends where the DNA has been cut are sticky in the sense that they will easily bind to another sequence of DNA that was cut with the same enzyme. A DNA sequence and a gene sequence to be integrated in the DNA sequence can both be cut with the same type of enzyme and their ends will stick together. The new DNA sequence will now have the gene inserted into it. The resulting product is called genetic engineered recombinant DNA.

There are basically two types of gene therapy. Germ-line gene therapy introduces genes into reproductive cells (sperm and eggs) or into embryos in order to correct genetic defects that could be passed on to future generations. Most of the current research, however, has been in the applications of somatic cell gene 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 patient. The main downside to this approach is that as each corrected cell dies, the therapeutic effects from gene therapy are lessened.