Our DNA has the power to unlock endless stories of who we are and where we came from, but what if we could change it forever? 44-year old Brian Madeux may be among the first to know: Last month, Madeux was the first individual to receive in-body gene editing, in an attempt to treat his Hunter Syndrome, a rare metabolic condition tied to a genetic mutation.
To carry out this groundbreaking therapy, scientists flooded Madeux’s body via IV with billions of copies of a corrective gene, as well as with a gene editor known as zinc finger nuclease (ZFN), intended to insert the new gene into his DNA.
Never before has an individual received permanent in-body DNA alterations to treat a genetic condition. Previously, scientists have tried altering cells in the lab, later injecting them into patients’ bodies, and have conducted a range of gene therapies that don’t involve altering DNA. However, these methods often provide only temporary or limited relief from many genetic conditions.
In contrast, any edits made using ZFN are immediate and irreversible: “We cut your DNA, open it up, insert a gene, stitch it back up. Invisible mending. It becomes part of your DNA and is there for the rest of your life,” explains Dr. Sandy Macrae, president of Sangamo Therapeutics, the California-based company behind Madeux’s procedure. Sangamo also plans to test ZFN’s success in treating hemophilia and other metabolic conditions.
ZFN therapy operates in several stages: scientists first insert instructions on how to activate zinc finger nucleases, which operate much like scissors slicing DNA, into a virus that’s altered to be harmless to human hosts. They then inject billions of copies of that virus, as well as a corrective gene, into the individual, where, following instructions, the virus travels to the liver. Once there, the virus spurs liver cells to create ZFN, which in turn trims the patient’s DNA at the precise site of a mutated gene, freeing up space for the corrective genes to enter the DNA.
As a monogenetic disorder, or one involving a mutation in just one gene, Hunter Syndrome provides a simple blueprint for researchers to test the therapy before moving on to conditions involving multiple mutations. Individuals suffering from Hunter are missing a gene that is key to producing an enzyme needed to process certain carbohydrates. The resulting build-up of carbs in their cells leads to widespread and permanent damage—everything from facial distortion and issues with bones, joints and bowels to problems hearing, seeing, breathing and thinking.
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