A human has been injected with gene-editing tools to cure his disabling disease

For the first time, researchers have infused a person’s blood with gene-editing tools, aiming to treat his severe inherited disease, The Associated Press (AP) reported today. The 44-year-old patient has a rare metabolic disorder called Hunter syndrome. But how big is the advance—and what does it mean for using hot new technologies such as CRISPR to help people with other genetic diseases?

How does the treatment work?
Hunter syndrome results from a mutation in a gene for an enzyme that cells need to break down certain sugars. When the enzyme is defective or missing, the sugars build up and can cause developmental delays, organ problems, brain damage, and early death. Brian Madeux, the first patient in what will be a small clinical trial has a mild form of the disease, but nevertheless has had more than two dozen operations as a result, AP reports.

Someday, researchers may be able to use gene editing to repair the flawed gene in cells that causes diseases like Hunter syndrome. However, that’s not the goal of the trial, sponsored by Sangamo Therapeutics, a biotech company based in Richmond, California. Instead, the company inserts a replacement copy of the gene, using gene editing to snip the DNA helix of liver cells in a specific place near the promotor, or on-off switch, for the gene for a protein called albumin. The cells fix the damage by inserting the DNA for the new gene, supplied by the researchers along with the gene editor’s DNA scissors, and the gene’s activity is then controlled by the powerful albumin promotor. The idea is to turn these modified liver cells into a factory for making the enzyme missing in Hunter syndrome.

Sangamo’s targeted approach, known as “safe harbor,” should avoid the risks of using traditional gene therapy to alter a cell’s genome, which pastes in the new gene at a random place in the genome and can potentially turn on a cancer gene. And because the body doesn’t need much of the enzyme, modifying just a small fraction of the liver’s cells should be enough to treat the disease.

Although Hunter syndrome patients often receive weekly infusions of the missing enzyme, their blood levels drop within a day, says Sangamo CEO Sandy Macrae. The hope is that the one-time gene-editing treatment—given as a 3-hour intravenous infusion—will allow the liver to keep making the enzyme at a steady rate for years. There is a caveat, however: The enzyme Hunter patients now receive does not cross the blood-brain barrier, the tight network of cells that protects the brain from pathogens, and the livermade enzyme produced by the gene edit may not either. So the new treatment may not stop the brain damage that can occur in Hunter syndrome.

http://www.sciencemag.org/news/2017/11/human-has-been-injected-gene-editing-tools-cure-his-disabling-disease-here-s-what-you

> snip the DNA helix of liver cells in a specific place near the promotor, or on-off switch, for the gene for a protein called albumin. The cells fix the damage by inserting the DNA for the new gene, supplied by the researchers along with the gene editor’s DNA scissors, and the gene’s activity is then controlled by the powerful albumin promotor. The idea is to turn these modified liver cells into a factory for making the enzyme missing in Hunter syndrome.

I like that, putting the gene into cells that excrete enzymes.

What worries me though is how many cells have to be CRISPRed for this to work? Not the whole liver obviously.

mollwollfumble said:

> snip the DNA helix of liver cells in a specific place near the promotor, or on-off switch, for the gene for a protein called albumin. The cells fix the damage by inserting the DNA for the new gene, supplied by the researchers along with the gene editor’s DNA scissors, and the gene’s activity is then controlled by the powerful albumin promotor. The idea is to turn these modified liver cells into a factory for making the enzyme missing in Hunter syndrome.

I like that, putting the gene into cells that excrete enzymes.

What worries me though is how many cells have to be CRISPRed for this to work? Not the whole liver obviously.

Over time if it works properly, all the liver cells will be replaced.

roughbarked said:

Over time if it works properly, all the liver cells will be replaced.

How?

Liver cells – hepatocytes – that excrete enzymes live for 300 to 500 days. Interestingly, fully differentiated hepatocytes can still reproduce. So if natural albumin production far exceeds the natural production of this enzyme then a single treatment could last a year, or less, or more. Depending on how traumatic the gene editing process is for the genetically modified cells.