There are an estimated 100,000 genes in the human body. By replacing defective genes with healthy ones, it will be possible to treat many hereditary diseases such as haemophilia, cystic fibrosis and, eventually, some forms of muscular dystrophy and cancer.
Rapid progress has been made in recent years in characterizing hereditary diseases and in understanding their causes. These diseases are due to alterations of genes, which encode the information for building the body and making it work. Genes are the carriers of hereditary traits and are contained in filaments of DNA (deoxyribonucleic acid) that are present in the cells of all organisms. The precise number of genes in the human body is unknown, but it is estimated to be around 100,000.
Every cell has two copies of each gene, one deriving from the father, the other from the mother. The information in the genes is used for making proteins, the agents for building the body and making it work. A disease appears when a gene is altered in such a way that either it does not make its corresponding protein, or else makes a protein that is incapable of functioning. Since the same protein is encoded in both genes of each pair, if only one fails enough protein continues to be made to satisfy the needs of the organisms, and there is no disease. A disease appears when both fail and no functional protein is made. This generally happens when a child is born from two healthy parents, each of whom carries an altered gene of the same pair. Such parents have a one-in-four chance of generating a defective child.
Hereditary genetic diseases can vary greatly in severity. At one extreme are diseases such as phenylketonuria, which, after detection at birth, can be completely prevented by adopting a suitable diet. At the other are those like Lesch-Nyhan syndrome, which affects only boys, causing a terrible form of mental retardation in which they tend to eat themselves and must be kept bound to their beds to prevent them from eating their fingers. Even so, they may eat their lips or their tongues. All hereditary diseases generate a degree of handicap, and for the majority of them there is not as yet any effective therapy.
Vectors and receptors
During the last ten years many of the genes responsible for hereditary diseases have been discovered, leading to the possibility of a new form of therapy known as "gene therapy" that is based on the introduction into the patient's cells of a good copy of the defective gene so as to perform the missing function. The concept is straightforward, but the implementation presents many problems, which so far have limited its use to only a few cases.
To treat a hereditary disease with gene therapy several conditions must be met. In the first place the gene responsible for the disease must be known and must be isolated in a form that contains all the information needed to make the protein. Many copies of the gene must be available, to maximize the number of cells into which it can be introduced. The fresh genetic material is usually inserted into the malfunctioning cells by means of a "vector" or carrier. Such vectors are often obtained from viruses; but many viruses may either kill cells or change them to cancer cells. To prevent these adverse effects the genes responsible for causing them are removed from the viruses.
The first vectors used in gene therapy were made from viruses known as "retro-viruses". However, retro-viral vectors have important drawbacks: they only enter into some types of cell, and then the gene they carry acts weakly. The major disadvantage is that they cannot become established in cells that do not multiply. More recently viruses of another kind, known as "adeno-viruses", have been used extensively because they can become established in cells that do not multiply. Today most gene therapy is being carried out using as a vector either adeno-viruses or other viruses with similar properties. …