About Gene Therapy

Genes and Genetic Disorders

The basic unit of DNA, genes are functional units of heredity passed down by our parents. We have between 30,000 and 40,000 genes1, which determine things like our hair color or the ability of our blood to clot (an ability lacking in hemophiliacs). Most genes create a unique protein that is used for a specific cellular function, therefore it is this expression of the gene that creates an effect; trouble often occurs if faulty genes cannot create their specific protein.

All of us have a few defective genes, but because we get two copies of most genes, one from each parent, these defective genes will most likely never affect our health2. However, when we receive the same gene defect from both parents, or the defective gene received is "dominant," genetic disorders reveal themselves.

Many disorders are not purely hereditary, but rather have a genetic link. These multifactorial disorders are the result of multiple gene mutations and environmental factors. Cancer, heart disease, and diabetes are among multifactorial disorders, which tend to affect more people than monogenic disorders (disorders—like sickle-cell anemia—resulting from only one specific gene). The number of variables that factor in to multifactorial disorders can make studying and treating them challenging.

What is Gene Therapy?

Gene therapy involves replacing, removing, introducing, or otherwise altering genes in order to prevent or treat disease. Some of the most common ways researchers are correcting faulty genes are by adding normal genes into the genome, replacing abnormal genes, selectively mutating abnormal genes, or by altering the degree to with a gene is turned "on" or "off."

In order to perform these actions, researchers must indentify the location of specific genes; understand how, when, and why the genes perform their specific functions; and have a way to deliver the new information to the genome. Delivering genes to their desired location is the job of a carrier molecule called a vector. The most commonly used vectors are viruses because viruses already have the ability to deliver foreign genes to cells. Viral vectors are altered so they no longer cause illness. There are also non-viral vectors.

Commonly used gene therapy vectors

Retrovirus (viral vector)
These viruses are very effective at targeting specific cells, but can only affect cells that are dividing. The carried genes are inserted randomly into the host cell's genome and as the cell divides, the newly inserted genes are duplicated along with the rest of the DNA. Although the possibility of an immune response are reduced by removing certain proteins in these viruses, one can occur causing illness and/or interferring the effectiveness of the gene therapy. Additionally, the random insertion location of the new genes could adversely affect other gene's function.
Adenovirus (viral vector)
The common cold belongs to this class of viruses, which are especially effective at targeting the respiratory and instestinal systems in humans as well as causing eye infections. Unlike retroviruses, adenoviruses are not integrated into the host cell's genome, so within a few weeks the cell will discard the foreign genetic material, and while both these types are capable of targeting specific types of cells, adenoviruses are able to infect both diving and non-dividing cell types effectively. Adenoviruses also have the potential to cause an immune response, although this possibility is reduced by the removal of certain proteins.
Adeno-associated virus (viral vector)
Unlike the other types of viral vectors, which carry double-stranded DNA, adeno-associated viruses can carry only small, single-stranded DNA. Adeno-associated viruses can easily infect both dividing and non-dividing cell types and can be programed to target specific types of cells. Typically, these vectors will not cause any immune response, and almost all of the time, they will integrate themselves at the same location within the genome of the host cell, reducing the possibility of conflicting with other gene functions.
Herpes simplex viruses (viral vector)
This typical human pathogen is effective at targeting the cells of the central nervous system. Although the introduced genes to do not integrate into the host cell's genome, the genes will remain for some time as a seperate, circle piece of DNA, replicating along with the rest of the DNA as the cell divides. Because it does not integrate with the rest of the genome, it does not interfere with other genes' functions.
Liposome (non-viral vector)
These created lipid spheres are similiar to a cell's own membrane. They attach to cells, which hopefully take up their genetic material, although they are not as effective at this as viruses. Liposomes also do not target specific types of cells, although unlike viruses, there is no limit to the amount of DNA they can carry. The genetic material in liposomes may be engineered to enter or not enter the genome of the host cell, but even when it is intended to integrate, it is not particularly effective at doing so. Lipsomes do not cause an immune response, but can be toxic, and are generally used in ex vivo3 gene therapy approaches.
Naked DNA (non-viral vector)
One of the simplist ways to deliver genes is the direct introduction of DNA. Although not nearly as effective at infecting cells as viruses, some cells will take up DNA that is not "packaged" in anything. Like liposomes, this introduction method places no limit on the amount of DNA which can be introduced, but also does not target specific cells. Although it is not toxic nor does it create an immune response, this approach requires large amounts of DNA and is best suited for ex vivo gene therapy approaches.


  1. According to the Human Genome Project; exact numbers are still debated.
  2. Exceptions to this are genes found on the male X and Y chromosomes; sons receive the X chromosome from their mother and Y from their father. Each cell, therefore, has only one copy of the genes on each chromosome, wheras women have two copies of the X chromosome.
  3. ex vivo gene therapy delivers the genes to target cells while they are outside the body. This way, their proper integration and effect can be determined before they affect the person receiving the therapy.