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Gene therapy 鈥� using genes to treat or prevent diseases 鈥� is already saving lives. But it鈥檚 still very much an experimental treatment used on a few individuals, rather than a routine therapy. CRISPR will help change that.
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For starters, it will be much cheaper and easier to develop treatments to the point where they are ready to test in animals and people. And these treatments should be safer. 鈥淚t鈥檚 a new age in gene therapy,鈥� says of the German Research Centre for Environmental Health in Munich.
Unlike germline engineering (see 鈥�Will CRISPR gene-editing technology lead to designer babies?鈥�), changes made using gene therapy can鈥檛 be passed on to children. The conventional technique involves adding extra DNA to cells, but there is no way to control where it lands 鈥� and if it lands in the wrong place it occasionally results in cancer. With CRISPR gene editing, DNA can be added to a precise spot. Even then it can sometimes be added to the wrong place, but ways to minimise this have already been developed.
What鈥檚 more, treating some diseases requires altering existing genes rather than adding new ones 鈥� and gene editing excels at this. If it proves safe, CRISPR could be used to modify cells in the body to treat a wide range of diseases.
The tricky part will be delivering the gene-editing machinery and new DNA to cells inside the body. Fortunately, biologists working on CRISPR therapies can take advantage of the decades of work spent creating tools for delivering conventional gene therapy. The most popular method is to use harmless viruses called AAVs to carry the new genes into cells.
Viruses carrying CRISPR components have already been used to , to find out what those genes do. The drawback is that AAVs can only carry 4700 bases of DNA 鈥� and the gene for the key CRISPR protein, called Cas9, is nearly this big (See 鈥�How does it work鈥�). That鈥檚 OK if the aim is just to disable an existing gene. But it won鈥檛 work for adding genes; there isn鈥檛 enough room in AAVs to carry both Cas9 and a gene.
Unexpected problems
There are already some ways around this size limit. Smaller alternatives to the standard Cas9 protein are being tested, for instance. It is also possible to split Cas9 in two, and deliver each half in a separate virus, leaving more room for the rest of the payload. This approach is likely to be less efficient, though, as at least two AAVs have to deliver their DNA to each cell.
Years of animal tests will be needed to ensure that CRISPR-based gene therapy is safe enough to try in people, and Bryan Cullen of Duke University in Durham, North Carolina, cautions that unexpected problems will almost certainly arise when human trials begin. Nevertheless, he is confident that the approach will work: 鈥淚t will lead to treatments within a decade,鈥� he says.
Read more: 鈥�CRISPR: The gene-editing revolution on our doorstep鈥�
(Image: NIBSC/Science Photo Library)
This article appeared in print under the headline 鈥淲ill gene therapy go mainstream?鈥�
