Gene Therapy

January 8, 2006

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.


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