How Gene Therapy Works

Viruses as Gene Therapy Vectors
© 2010

Viruses perplexed biologists for years. They could see the effects of viruses -- illness -- but they couldn't isolate the infecting agent. At first, they thought they were dealing with extremely small bacteria cells. Then, amid a flurry of interest in viruses, American scientist Wendell Stanley crystallized the particles responsible for tobacco mosaic disease and described viruses for the world in 1935.

These strange entities don't have nuclei or other cellular structures, but they do have nucleic acid, either DNA or RNA. This small packet of genetic information is packed inside a protein coat, which, in some cases, is wrapped in a membranous envelope.

Unlike other living things, viruses can't reproduce on their own because they don't have the necessary cellular machinery. They can, however, reproduce if they invade a cell and borrow the cell's equipment and enzymes. The basic process works like this:

  1. A virus enters a host cell and releases its nucleic acid and proteins.
  2. Host enzymes don't recognize the viral DNA or RNA as foreign and happily make lots of extra copies.
  3. At the same time, other host enzymes transcribe the viral nucleic acid into messenger RNA, which then serves as a template to make more viral proteins.
  4. New virus particles self-assemble, using the fresh supplies of nucleic acid and protein manufactured by the host cell.
  5. The viruses exit the cell and repeat the process in other hosts.

That ability to carry genetic information into cells makes viruses useful in gene therapy. What if you could replace a snippet of viral DNA with the DNA of a human gene and then let that virus infect a cell? Wouldn't the host cell make copies of the introduced gene and then follow the blueprint of the gene to churn out the associated protein? As it turns out, this is completely possible -- as long as scientists modify the virus to prevent it from causing disease or inducing an immune reaction by the host. When so modified, such a virus can become a vehicle, or vector, to deliver a specific gene therapy.

Today, researchers use several types of viruses as vectors. One favorite is adenovirus, the agent responsible for the common cold in humans. Adenoviruses introduce their DNA into the nucleus of the cell, but the DNA isn't integrated into a chromosome. This makes them good vectors, but they often stimulate an immune response, even when weakened. As an alternative, researchers may rely on adeno-associated viruses, which cause no known human diseases. Not only that, they integrate their genes into host chromosomes, making it possible for the cells to replicate the inserted gene and pass it on to future generations of the altered cells. Retroviruses, like the ones that cause AIDS and some types of hepatitis, also splice their genetic material into the chromosomes of the cells they invade. As a result, researchers have studied retroviruses extensively as vectors for gene therapy.

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