Viruses in Gene therapy: How to Create a Virus: Adenovirus, Retrovirus, Adeno-associated Virus.
Creating a Virus
In nature there is a constant creation of viruses. A virus is the simplest form of genetic material. Although a virus can contain a DNA (or RNA) molecule it cannot, by itself, replicate. It needs a host cell for that purpose.
Viruses are implicated in many of the worst infections that humans endure (chickenpox, influenza, AIDS, etc) but they could be successfully used for treating other diseases. For example, different types of cancers could be someday cured by using viruses as vectors to deliver good working-genes to certain tissues or organs of the body where a faulty gene is causing trouble. Gene therapy takes advantage of the viral ability to transfer its genetic material into cells.
A retrovirus is a virus that contains ribonucleic acid (RNA) instead of DNA as the genetic material. As with any type of virus, a retrovirus requires a host cell to replicate. The retrovirus replication proceeds by the fabrication of a DNA molecule from the RNA template (using the host cell enzyme known as reverse transcriptase). Then, the recently synthesized DNA is incorporated into the host cell´s DNA and expressed using the whole host-cell enzymatic machinery.
Contrary to retroviruses, an adenovirus is a naked virus. They are quite large (with respect to other viruses) and have DNA as the genetic material for replication. The DNA is a linear molecule (not condensed or twisted) with the information to propagate using the host-cell’s replication machinery. They replicate in the nucleus of the host cell. Conjunctivitis, tonsillitis, ear infections, gastroenteritis, and even meningitis can be caused by adenoviruses.
Adeno-associated viruses (AAV) are small viruses which seem not to be involved in any disease. However, AAVs produce a slight immunological response from host cells and tissues. Because of AAV’s apparent lack of malignity, they are being studied as possible vectors for gene therapy trials. For example, researchers have been able to “cure” rats and mice with inherited Insulin-Dependent Diabetes Mellitus (IDDM) by injecting their bodies with millions of copies of an AAV containing a cDNA molecule encoding a synthetic version of insulin. Also, researchers have reported curing hemophilia B in mice using AAV plus the required gene for making a clotting factor.
Wang et al. (1999). Sustained correction of bleeding disorder in hemophilia B mice by gene therapy. Proceeding National Academy of Sciences (PNAS) vol. 96 no. 7 3906-3910
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