Genetic patch treats ‘bubble-boy’ disease

Some fascinating research has been published in the latest Nature. A new technique is being designed to successfully patch up the mutated gene underlying a rare disease called severe combined immunodeficiency disease (SCID), a.k.a. the ‘bubble-boy’ disease. The technique has a promise to be extended to a wide range of genetic disorders:

To repair the faulty gene, a team led by Michael Holmes of Sangamo Biosciences in Richmond, California, first engineered a protein that was able to comb through the millions of letters in the human DNA code to find a single 24-letter sequence within the defective gene that causes SCID. They fused this protein to an enzyme that snips through DNA at that site.
The researchers aimed to insert this enzyme into human cells, along with a fresh piece of DNA that matched the defective gene but lacked the mutation. Severing the DNA triggers a repair process called recombination, in which the cell attempts to patch up a cut by swapping the entire region with an undamaged segment, in this case, the unmutated DNA sequence.
In a trial experiment, the team showed that it could alter the gene underlying SCID in around 20% of human immune cells, which are the cells destroyed by the disease. The technique cannot currently be used to correct cells within the body, but the researchers think they could extract stem cells, which give rise to the affected immune cells, correct their mutations, and put them back into the patient’s body to restock the immune system.
Researchers at Sangamo are also developing their technique to tackle HIV. Rather than correct a mutation, the idea is to introduce a defect into a gene in immune cells, so that they no longer allow the virus to enter.
Indeed, the study suggests that researchers could design similar enzymes that recognize and cut DNA at any point in the human genome, potentially triggering almost any change or repair. “It’s very powerful,” says geneticist John Wilson of Baylor College of Medicine in Houston, Texas. “I’m really enthusiastic about this.”
Researchers discovered more than 20 years ago that they could entice mammalian cells to swap one segment of DNA for another by recombination. But the process occurs spontaneously in only one in a million cells: far too few to have any impact on disease.
In the past few years, however, scientists have begun to tailor enzymes like the one used by Holmes, which snip DNA at a particular spot and hugely bump up the rate of recombination. They do this by mixing and matching an array of proteins that recognize and bind to specific three-letter sequences of DNA. By sandwiching together eight of these proteins, for example, they can design one that binds to a chosen 24-letter sequence.
Holmes’s team is the first to design an enzyme that successfully recognizes a mutated gene underlying human disease, and to show that it prompts efficient gene repair.

More at Nature…