Cut, Copy, Paste, Repeat


George Merrin delves into the science behind gene therapy.

FOR most people gene therapy is something from futuristic television shows and films and not a fact of today’s reality. Gene therapy is something which scientists and investors place a huge amount of time and effort in, to try cure incurable diseases and help improve people’s quality of life. But what exactly is gene therapy?

Gene therapy is where a defective gene is replaced with a correct one. A gene is a tiny segment of your DNA, which encodes for proteins that allow us to do everything from see to fight disease. Genetic disorders occur when there is a problem with one or more gene, which has the knock-on effect of misfolding the associated proteins. Sometimes these misfolded proteins can hugely benefit us, but usually they result in diseases such as sickle-cell anaemia and Parkinson’s Disease.

Gene therapy works on the principle of inserting a correct copy of the gene into the cell which will replace the old copy of the gene, then as the cell further divides each subsequent cell will have the correct copy. There are several issues with this.

Gene therapy is extremely expensive. The drug Glybera consists of viruses with correct copies of the lipoprotein lipase gene and in 2012 was the most expensive drug in the world with a value of $1.6 million. As well as that, due to the rapid division of cells, one treatment often isn’t enough. This can increase the already extravagant cost.

There are two main ways gene therapy is undertaken, viral and non-viral. Viruses are often better than non-viral means. The correct gene is inserted into a viral vector, i.e. a genetically engineered virus, which can then be injected into the recipient. However, viruses can trigger immune responses, which can be fatal.

In 1999, the first known death occurred in a gene therapy trial. Jesse Gelsinger died four days after receiving treatment for ornithine transcarbamylase deficiency, which is a liver condition. This trial was shrouded in controversy as Gelsinger was only added to the trial after a volunteer dropped out.

Gelsinger himself would have been unable to participate in the trail as he had high levels of ammonium, the by-product that his disease couldn’t metabolise. A rebuttal was issued by the University of Pennsylvania and his parents were paid a settlement.

Gene therapy is limited by the complexity of the disorder. Disorders such as high blood pressure and Parkinson’s Disease occur because of problems with several genes. These are referred to as multigene disorders and are very complex. This largely restricts what can be done to treat them. There are two classes of cells, somatic and reproductive/germline. Somatic cells are all cells that are non-reproductive. Gene therapy of somatic cells does not affect future offspring whereas germline therapy does. The divide between these two types is referred to as the Weissman barrier. Currently the Netherlands, Israel, Australia, Germany, Switzerland, and Canada all prohibit germline therapies.

There are several techniques for inserting the correct copy of a gene into your DNA. One of these is CRISPR, or Clustered Regulatory Interspaced Short Palindromic Repeats. To put this simply, every so often in the genome there are short sequences which can be spliced and then a new copy inserted into the space created as they match the sequence.

This new technology is fast and specific and it also reduces the chances of creating things like tumours by damaging tumour suppressor genes. Changes like this are called insertional mutagenesis. CRISPR is currently being used to modify human T-cells to attack cancerous cells.

With all of the benefits of gene therapy such as the ability to eradicate many diseases, there is also the ability to modify human capabilities, i.e. create super soldiers. This technology has lots of potential, but as with all science we must proceed with caution.

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