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With fewer than 10,000 affected people around the world, Hunter syndrome is a rare genetic condition that leaves the sufferer without an enzyme that is used to break down complex polysaccharides, a carbohydrate.
Patients may have frequent colds and ear infections, distorted facial features, hearing loss, heart problems, breathing trouble, skin and eye problems, bone and joint flaws, bowel issues and brain and thinking problems. Weekly IV doses of the missing enzyme can ease some symptoms, but cost $100,000 to $400,000 a year and don't prevent brain damage. Left untreated, it can cause permanent damage to mental development, organ function and physical abilities, leading to an early death.
In this case, doctors have attempted to correct the condition by using zinc finger nucleuses (ZFNs). These enzymes cut a gene that is present in liver cells, inserting a functional copy of the gene that produces the desired enzyme.
The treatment was developed by Sangamo Therapeutics, a biotechnology firm based in California. This is the first time someone could have a new gene put into their liver, as per the Company’s president and CEO, Sandy Macrae, in an interview with The Scientist.
Procedure:
The therapy has three parts:
- The new gene and two zinc finger proteins. DNA instructions for each part are placed in a virus that's been altered to not cause infection but to ferry them into cells. Billions of copies of these are given through a vein.
- They travel to the liver, where cells use the instructions to make the zinc fingers and prepare the corrective gene.
- The fingers cut the DNA, allowing the new gene to slip in. The new gene then directs the cell to make the enzyme the patient lacked.
Only 1 percent of liver cells would have to be corrected to successfully treat the disease.
ZFNs are a more unwieldy method of performing gene editing than CRISPR Cas-9, but they do offer more precision, producing very specific and highly effective zinc finger nucleases. The implementation utilized by Sangamo reportedly offers the ability to cut at any base that might be required, and being able to place the new gene in exactly the right location.
A successful trial like this demonstrates how far we’ve come in terms of being able to make edits to the human genome. Between CRISPR and ZFNs, we have developed powerful tools that allow us to make precise modifications – and that will allow us to treat a wide variety of different conditions.
This procedure is part of a larger trial being carried out by Sangamo, which will also consist of experimental treatments for people suffering from hemophilia B and Hurler syndrome, as well as Hunter syndrome. All three diseases are caused by absent or non-functional genes, which can now be inserted thanks to these cutting-edge techniques.
The use of ZFNs to treat Hunter syndrome offers up a huge improvement over the way the disease is addressed at present. The current method typically involves weekly infusions of enzyme replacement therapy. While this has proven to be effective, since the patient isn’t actually producing the enzymes, it’s an ongoing treatment that consumes a lot of time and money.
Conversely, ZFNs make lasting changes to the human body that remove the problem entirely. It’s easy to see how this technique could have a huge impact on the patient’s quality of life – it’s a matter of nipping the issue in the bud, rather than addressing it continually.
Can things go wrong?
The virus might provoke an immune system attack. In 1999, 18-year-old Jesse Gelsinger died in a gene therapy study from that problem, but the new studies use a different virus that's proved much safer in other experiments.
Inserting a new gene might have unforeseen effects on other genes. That happened years ago, when researchers used gene therapy to cure some cases of the immune system disorder called "bubble boy" disease. Several patients later developed leukemia because the new gene inserted into a place in the native DNA where it unintentionally activated a cancer gene.
The virus could get into other places like the heart, or eggs and sperm where it could affect future generations. Doctors say built-in genetic safeguards prevent the therapy from working anywhere but the liver, like a seed that only germinates in certain conditions.
So it appears the scientists have considered all that could potentially go wrong - now we have to wait to see the outcome over time with this procedure.
The next step for the scientists in the company and others will be to figure out how this technique might be used to treat other conditions.
References: Futurism; The Scientist; Medical Xpress;
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