Although gene therapy is defined as any treatment that changes gene function, it is often thought of as the insertion of normal genes into the cells of a person who lacks such normal genes because of a specific genetic disorder (gene insertion therapy). The normal genes can be manufactured, using polymerase chain reaction (PCR), from normal deoxyribonucleic acid (DNA) donated by another person. Currently, such gene insertion therapy is most likely to be effective in the prevention or cure of single-gene defects, such as cystic fibrosis.

The transfer of the normal DNA into a person's cells can be done by several methods. One method is to use a virus, because certain viruses have the ability to insert their genetic material into human DNA. The normal DNA is inserted by a chemical reaction into the virus, which then infects (transfects) the person's cells, thereby transmitting the DNA into the nucleus of those cells. One of the concerns about insertion using a virus is potential reactions to the virus, similar to an infection. Another concern is that the new, normal DNA may become “lost” or may fail to be incorporated into new cells after some period of time, leading to the reappearance of the genetic disorder. Also, antibodies may develop against the virus, causing a reaction similar to the rejection of a transplanted organ.

Another method for inserting genes uses liposomes, which are microscopic sacs containing the DNA that are absorbed by the person's cells, thereby delivering their DNA to the cell nucleus. Sometimes this method does not work because the liposomes are not absorbed into the person's cells, the new gene does not work as intended, or the new gene is eventually lost. A third method is called naked plasmid DNA injection, in which plasmid DNA (a special circular form of DNA) is injected into a person's muscle.

A different method of gene therapy uses antisense technology, in which, rather than inserting normal genes, the abnormal genes are simply switched off. Using antisense technology, drugs can combine with specific parts of the DNA, preventing the affected genes from functioning. Antisense technology is currently being tried for cancer therapy but is still very experimental. However, it seems to have the potential to be more effective or safer than gene insertion therapy.

Another approach to gene therapy is to increase or decrease the activities of certain genes by modifying chemical reactions in the cell that control gene expression. For example, modifying a chemical reaction called methylation can change the function of a gene, causing it to increase or decrease production of certain proteins or to produce different kinds of proteins. Such methods are being tried experimentally to treat certain cancers.

Gene therapy is also being studied experimentally in transplantation surgery. By altering the genes of the transplanted organs to make them more compatible with the recipient's genes, the organ recipient is less likely to reject the transplanted organ. Thus, the recipient may not need to receive drugs that suppress the immune system, which can have serious side effects. However, this type of treatment is usually unsuccessful.

Last full review/revision August 2007 by Judith G. Hall, MD