A major problem in treating genetic disorders is the inability to precisely target and remove or change the offending genes, known as gene therapy. If you can take a person's problem cells out of his or her body, modify the dysfunctional genes, and put the modified cells back into the person's body, then you can most likely treat/cure the disorder. All of the steps in this process are complicated, though, and it's been extremely difficult to "cure" a genetic disorder in this way. First, due to the lack of homologous recombination, it's not easy to target genes in somatic cells, so tricks need to be used to modify the genes of interest. Second, most of the targeted cells would not be "fixed" due to the low efficiency of successful modification. Third, it's extremely challenging, maybe impossible, to modify cells in organs or other solid tissues because they can't be manipulated in a lab or efficiently exposed to the therapy, so gene therapy has generally been restricted to blood disorders, where a person's blood cells can be removed and modified in a lab setting, while all residual dysfunctional blood cells in the body are killed through radiation.
Early ideas of gene therapy involved the use of viruses that could modify or introduce DNA into human cells, theoretically removing the dysfunctional genes or introducing helpful genes to cells that could be re-introduced into the patient's body. However, there were problems with these early trials, mainly that they sometimes caused these cells to grow out of control, like a cancer. It was too high a risk to take with human lives, so this research has not moved forward as much as people would have liked.
A new group of tools has been developed in the last few years that might now allow researchers to use gene therapy to treat or cure genetic disorders. These tools help with the first (and to a lesser extent, the second) problem: they can specifically target genes of interest inside cells, allowing specific mutations or deletions to be made in dysfunctional genes, possibly at a higher efficiency than was possible with the older virus-based tools.
The first tool is known as the ZFN, or zinc finger nuclease, developed by Sangamo BioSciences in Richmond, CA (disclosure: members of my lab are collaborating with Sangamo to test ZFNs in human cell lines and recently published an article on their research). This is a combination of two different proteins, the zinc finger transcription factor and a DNA-modifying endonuclease. The zinc finger is what targets a specific three-letter DNA sequence (codon) in the genome, and the endonuclease makes a cut at that specific region. This can be used to both disrupt a gene and add to a gene. Sangamo has licensed its technology to Sigma-Aldrich, which sells ZFN constructs for $25,000 apiece.
The second tool, called the Genesis system, is based on adeno-associated viruses (AAVs) and has been developed by Horizon Discovery in the UK. Their technology, named Genesis, seems to be more flexible than the ZFNs in that they can add genes as easily as they can delete them. The technology uses AAVs that contain single-stranded DNA sequence that is homologous to the sequence of the target gene. This company has not licensed its technology to a large biotech, but it has collaborated with Novartis on a pilot study and is working with a number of academic institutions (called Centers of Excellence) to use this technology. Horizon Discovery seems to collaborate with these academic institutions free of charge, but it charges industry clients between $20,000 and $50,000 per cell line, depending on the level of customization.
The third tool has been developed by the French company Cellectis. This technology, similar to ZFNs, is called transcription activator-like effector nucleases, or TALENs. They make use of enzymes called meganucleases, which cut at specific DNA regions. The major difference is that TALENs can target individual DNA nucleotides rather than the three-nucleotide codons that are targeted by ZFNs. Cellectis offers TALEN constructs for $5,000 and up.
Together, these new technologies represent the next leap in human genetic disease (and animal model of human disease) research. These technologies could solve some of the problems plaguing gene therapy research, and they could set us forward many years in our ability to precisely modify human and mouse genes for the purposes of treating and curing diseases.