State of the Art: GENE THERAPY- Pt 1

What is Gene Therapy?

Gene therapy is the term used for a biological treatment that is designed to introduce new active genetic material to living cells in order to increase or reduce a genetic product or products. These products can include either RNA or proteins or both. For the crudest of analogies, imagine the cell is a factory. This factory has assembly lines that currently build blenders. The blenders are great, but you also want to make toasters now. You send instructions to the factory to reconfigure some of its assembly lines to make toasters for at least part of the time. That is basically what is happening in gene therapy.

The most easily related example that I can think of where this technology could be useful is in Type I diabetes mellitus, where there is a deficiency in production of the protein, insulin, which is encoded by DNA on chromosome 11 in humans. An easy illustration of how a gene therapy could work would be to say that the gene for insulin production could be introduced to cells of a Type 1 diabetes patient so that their body would then be capable of generating insulin on their own. They would no longer need to take insulin shots to control high levels of blood sugar. I will stop there and now posit the emphatic caveat that the case of Type 1 diabetes is much more complex than I just described. The lack of insulin production is not because a gene is missing, rather it is because the cells that normally produce insulin are missing. In fact, diabetes might be better treated with a stem cell therapy than a gene therapy; but I digress (a topic for another State of the Art series). The main point of this ambling monologue is that, by using gene therapy, a new gene or genes can be introduced so that a cell can generate a product that it wasn’t previously generating in order to achieve a variety of net effects.

In the United States, there are currently as many as 30 clinical trials active or enrolling to test the safety and efficacy of myriad gene therapy, or gene transfer, strategies. The trials hope to find treatments for conditions ranging from X-linked Chronic Granulomatous Disease (CGD) where patients’ neutrophils cannot make a key protein necessary for infection defense to Advanced Pancreatic Cancer where a researchers are trying to test safety and dose response of delivering a “tumor killing” gene.

While there are dozens of gene therapy clinical trials and hundreds of labs worldwide conducting research with gene therapy technologies, there is still no FDA approved gene therapy product on the market; nearly 17 years after the first human gene therapy trial was conducted on a 4 year old girl with severe combined immunodeficiency (SCID) at the U.S. National Institutes of Health in 1990.

Why are gene transfers so challenging to develop and administer? There are many pitfalls. First of all, it is simply difficult to incorporate new genes into living cells, especially in a multicellular tissue system. Secondly, once the gene is there, it doesn’t always produce an active protein (or RNA). Thirdly, if the gene does work, it is very difficult, if not impossible, to turn it off, thereby rendering overdoses and immune reactions virtually impossible to treat. Forthly, it is difficult to target genes to show up in the correct cells while not also affecting cells that don’t need the gene. Lastly, there are some questions about potential to pass on the therapeutic gene to offspring who won’t need it.

These issues are currently being addressed with variable success in research around the world. They are testing many different genes and gene deliver strategies in hopes of harnessing biology’s machinery to treat diseases. In the next installments of State of the Art: GENE THERAPY, we will talk about specifics of where the technology is right now. For now, chew on this one. Think of questions. Tell me I am an idiot. Thanks for reading. :)

Upcoming Posts!

State of the Art: GENE THERAPY- Pt2
Viral Delivery

State of the Art: GENE THERAPY- Pt3
Non-Viral Delivery