Gene Therapy

Gene Therapy

Gene therapy is a technique for fixing genetic disorders by inserting cloned genetic material into cells to repair or replace dysfunctional genes. Currently there are four approaches to gene therapy:

  • A functional gene is inserted (nonspecifically) into the genome to take cover for a nonfunctional gene. This is the most common approach.
  • An abnormal gene is replaced by a normal gene through homologous recombination. (see gene-targeting)
  • The abnormal gene is repaired through specific reverse mutations, which returns the gene to normal function.
  • Gene regulation can be altered by inserting promoters or interrupting promoters.

How it works
The most common gene therapy approach is to use a functional gene to replace a dysfunctional disease causing gene. The gene is inserted into a target cell via a vector. Vectors are biological agents that transfer genetic material from one cell to another. Currently, ‘domesticated’ or genetically-modified viruses are the most common type of vector.

Viral vectors infect the target tissue and insert the designated genes into the host cells. For example, gene therapy for diabetes would target the cells of the pancreas responsible for insulin production. If the therapeutic gene is expressed, the cell is able to produce the protein or proteins that it had been missing – alleviating the genetic disorder.

Common Viral Vector Classes:

  • Retroviruses – A type of virus that has an RNA genome and reverse-transcribes double stranded DNA that can be integrated into the host genome.
  • Adenoviruses – Viruses with with double-stranded DNA genomes. Adenoviruses are responsible for many mundane human illnesses such as the common cold.
  • Adeno-associated viruses – Virus with a single stranded DNA genome. They are unique in that they can incorporate their genetic material into a specific place – chromosome 19.
  • Herpes simplex viruses – Viruses with double stranded DNA genomes that solely target genomes. Their specificity makes them particularly useful as vectors for neuronal diseases.

Some researchers are investigating nonviral vectors. This approach takes advantage of natural cellular processes such as endocytosis. For example, some scientists are exploring the use of artificial lipid globules to introduce the transgenes into the cell. A similar strategy is to attach the transgene to a cell membane receptor agonist. When the agonist binds to the receptor it initiates endocytosis, delivering the transgene into the cell. So far these delivery systems are not as effective as the viral vector systems.

One intriguing new approach is the creation of an artificial 47th chromosome to introduce into the target cells. Because the transgene no longer has to be incorporated into one of the cells natural chromosomes, there is no risk of insertional mutations. This approach has the added advantage of not interfering with the cells pre-existing expression pattern. Furthermore, because this strategy uses a whole chromosome, Very large amounts of genetic material can be added allowing for more sophisticated design. Also the chromosome could potentially be designed in a way that would avoid an immune reaction. However, the size of the transgenic element, creates additional difficulty in getting it inot the nucleus of the target cell.

Current Status of Gene Therapy

After more than twenty years of gene therapy, there are still no publicly available gene therapy regimens. After early success in (in vitro) experiments, application to humans has proved to be surprisingly problematic. The clinical trials began in 1990, but have been plagued by technical problems ever since. In fact, serious health complications and deaths in a number of recent clinical trials has raised calls for increased regulatory scrutiny over future clinical trails. For example, in January 2003, the FDA placed a temporary halt on all gene therapy trials using retroviral vectors in blood stem cells after two children in a French gene therapy trial developed a type of Leukemia.


  • 1980 – Richard Mulligan, an M.I.T. researcher, shows that genetically engineered mouse-leukemia retroviruses were effective messengers for carrying human genes into mouse DNA.
  • 1989 – Dr. French Anderson, Eli Gilboa and Dr. Michael Blaese win approval from an National Institutes of Health (NIH) advisory panel for a test that would transfer bacterial genes into immune cells of terminal cancer patients. The trial paves the way for dozens of gene-therapy efforts.
  • 1990 – Dr. French Anderson and Michael Blaese perform the world’s first officially approved gene therapy by manipulating human genes. The patient is a 4 year-old girl named Ashanti DeSilva. She inherited a defective gene from both parents and suffered from ADA (adenosine deaminase) deficiency. The scientists introduce millions of Ashanthi’s own white blood cells into her bloodstream that were extracted from Ashanthi’s blood and genetically engineered to contain a corrected (”therapeutic”) copy of the adenosine deaminase gene. The scientists hope these cells will restore Ashanthi’s immune function by producing a normal version of the defective enzyme. The treatment appears to have been a success.
  • 1999 – The sudden death of Jesse Gelsinger, a patient undergoing experimental treatment for a rare liver disorder at the University of Pennsylvania, raises scores of questions about various aspects of gene therapy. Penn officials say Gelsinger’s immune system had a severe inflammatory reaction that caused multiple organs in his body to fail.
  • 1999– NIH discovers that researchers did not report 6 gene therapy patient deaths. Public backlash intensifies
  • 2000 – Reporters uncover hundreds of unreported cases of “adverse effects” for gene therapy trail.
  • 2001 – First germline gene transfer – 30 children born as a result of ooplasmic transfer. Ooplasmic transfer (also referred to as ooplasmic or cytoplasmic transplantation) is a fertility procedure used by women who cannot conceive because of defects in their ooplasm – their eggs’ cytoplasm. The procedure is performed by inserting healthy ooplasm from donor eggs into the eggs with defective ooplasm. By inserting healthy ooplasm from the donor eggs into the mother’s defective eggs, a small amount of mitochondrial DNA is transferred into the egg. This is considered germline gene transfer because the mitochondrial DNA of these children, and of their offspring, will always be from the donating mother.
  • 2002 – Two children who were cured of “bubble baby syndrome” (X-SCID), were discovered to have developed a leukemia-type disease.
  • 2003 – FDA temporarily halts gene therapy trials using retroviral vectors in blood stem cells. This is the first restriction of government regulation of gene therapy trails since they were allowed in 1989.

The Current Obstacles


  • Short-lived nature of gene therapy – Before gene therapy can become a permanent cure for any condition, the therapeutic DNA introduced into target cells must remain functional and the cells containing the therapeutic DNA must be long-lived and stable. Problems with integrating therapeutic DNA into the genome and the rapidly dividing nature of many cells prevent gene therapy from achieving any long-term benefits. Patients will have to undergo multiple rounds of gene therapy.
  • Immune response – Anytime a foreign object is introduced into human tissues, the immune system is designed to attack the invader. The risk of stimulating the immune system in a way that reduces gene therapy effectiveness is always a potential risk. Furthermore, the immune system’s enhanced response to invaders it has seen before makes it difficult for gene therapy to be repeated in patients.
  • Problems with viral vectors – Viruses, while the carrier of choice in most gene therapy studies, present a variety of potential problems to the patient –toxicity, immune and inflammatory responses, and gene control and targeting issues. In addition, there is always the fear that the viral vector, once inside the patient, may recover its ability to cause disease.
  • Multigene disorders – Conditions or disorders that arise from mutations in a single gene are the best candidates for gene therapy. Unfortunately, some the most commonly occurring disorders, such as heart disease, high blood pressure, Alzheimer’s disease, arthritis, and diabetes, are caused by the combined effects of variations in many genes. Multigene or multifactorial disorders such as these would be especially difficult to treat effectively using gene therapy.


  1. thanks for this info
    i needed it for assignment

  2. gee wiz this info was soooo useful I am glad it’s here thanks

  3. The papers or reports that mention “adverse effects” mentioned around 2000, where can I find that documentation? Thanks nb

  4. Plagiarized much?

  5. author?????

  6. hi, that’s a respectable install. There is whatsoever mistakes but the water is here.

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