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Gene Therapy


Quasar S. Padiath

, MBBS, PhD, University of Pittsburgh

Reviewed/Revised Jun 2023

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. This technique is called gene insertion therapy or insertion gene therapy.

The transfer of the normal DNA into a person’s cells can be done by several methods.

Viral transfection

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 that have a layer of lipid (fat). Liposomes can be configured to contain DNA that can be 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.

Antisense technology

A different method of gene therapy uses antisense technology. In antisense technology, normal genes are not inserted. Instead, the abnormal genes are simply switched off. Using antisense technology, modified RNA molecules can combine with specific parts of the DNA, preventing the affected genes from functioning. Antisense technology is currently being used for the treatment of spinal muscular atrophies Spinal Muscular Atrophies (SMAs) Spinal muscular atrophies are hereditary disorders in which nerve cells that originate in the spinal cord and brain stem degenerate, causing progressive muscle weakness and wasting. The five... read more and Duchenne muscular dystrophy Duchenne Muscular Dystrophy and Becker Muscular Dystrophy Muscular dystrophies are a group of inherited muscle disorders in which one or more genes needed for normal muscle structure and function are defective, leading to muscle weakness of varying... read more . It is also being tried for cancer therapy and some neurologic disorders, but it is still very experimental. It seems to have the potential to be more effective and safer than gene insertion therapy.

Chemical modification

Another approach to gene therapy is to increase or decrease the activities of certain genes by using chemicals to modify 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.

Transplantation therapy

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, so far, this type of treatment is usually unsuccessful.


CRISPR-CAS9 stands for clustered regularly interspaced short palindromic repeats–CRISPR-associated protein 9. CRISPR-CAS9 is a gene-editing tool that makes a precise cut in a DNA strand, and then the normal DNA repair process takes over to incorporate a newly inserted gene into the DNA. This technique is still in experimental stages but has been done on several human embryos in attempt to fix a genetic defect.

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