Researchers would love to be able to correct the altered DNA responsible for EB. Treatments can try to reduce the unwanted inflammation and scarring or replace missing or damaged proteins (collagen or keratin) but actually changing the DNA sequence of the genes coding for those proteins, could potentially resolve all the symptoms and provide a real cure. But there are more than three billion (3,000,000,000) bases (letters) in the human genome. Changing just one of these, in just one of our 20,000+ genes, without messing up any of the others, is a bit of a challenge. 

We have more than 37 trillion (37,000,000,000,000) cells in our bodies although not all of them make keratin or collagen. Changing the sequence in enough of the cells that need it to make a difference is a challenge. Targeting a genetic change to just a certain type of cell is also important as there are ethical issues if genetic changes are made that affect the eggs and sperm cells (germline cells). Any changes affecting these cells would be passed on to a person’s children without their consent along with any, as yet unknown, negative affects the changes could potentially have.

Gene editing is a type of genetic modification that is based on naturally occurring methods used by bacteria to protect themselves from viruses.

CRISPR/Cas9 is a specific type of gene editing that has a great deal of potential. Clustered regularly interspaced short palindromic repeats (CRISPR) are short pieces of virus genomes that bacteria steal and stick into their own genomes after being infected by those viruses. If they encounter a similar virus again, they can create copies of these sequences that match with the viral genome and stick to it. A protein like the enzyme Cas9 (CRISPR-associated protein 9) sticks to the CRISPR copies so is targeted to the viral genome where it chops it up and disables the virus.

Researchers could use this system to make targeted cuts in the human genome that remove harmful changes and use other natural cell processes that fix genetic damage to add in corrected sequence. 

Currently CRISPR-Cas9 gene editing is ethically used only in animals or in human cells grown in laboratories as there is not yet enough evidence that it is safe to use on an entire human body. If changes are made to somatic cells (not eggs and sperm), they will be limited to that individual person’s body. Genetic changes to germline cells (eggs and sperm) have the potential to be passed on to an individual’s children, grandchildren and descendants forever. Those people, as yet unborn, have no ability to consent to changes to their genome and the risks of potential harm make gene editing of human germline cells or embryos illegal in many countries.

In the UK, genome editing can be legally used on humans where the genetic change will not be passed on to children including in early embryos that will never be returned to a mother for implantation and will not progress beyond 14 days of development.


CRISPR explained

Image credit: 30728289683, by National Human Genome Research Institute