While are born with some mutations, we acquire others that can lead to cancer as we travel through life and are exposed to a range of carcinogens, from medical radiation to pesticides. Wouldn't it be great if we could periodically identify the dangerous mutations and fix them? A new technology may just provide that solution, in a decade or two.
Since the genetic code was determined to contain mutations, researchers have been searching for a way to find the “typos” and correct them. There have been a few techniques available to basic scientists but they were difficult to use and not as precise as one would want. Now a new tool called CRISPR-Cas9, developed by Emmanuelle Charpentier and Jennifer Doudna, has changed all that. All the tools measure enzymes, called nucleases, that can be directed to find a particular sequence of base pairs (alphabet of DNA) and cut the DNA strand at that exact point. The body then immediately works to repair the damage either by fixing the break or more elegantly inserting new genes based on a DNA repair guide that came with the cutting machine. This is much like the “find and replace” function in your word processor, and results in edited DNA. It is a vast improvement over the former technique of gene therapy which depends on a virus to randomly insert a new piece of DNA with the hope that no matter where it lands it will perform correctly. As one article put it, it is like replacing a deflated tire rather than attaching a fifth tire to your car.” (Nature 528 3 December 2015 S4).
The CRISPR-Cas9 system is part of the adaptive immune system found in bacteria. In fact, the term CRISPR stands for “clustered regularly interspaced short palindromic repeats” and is meant to describe the small segments of genetic material that bacteria capture from invading viruses and store in their own genomes for future reference. The Cas9 part of this team normally comes into play when threatened by a virus. It checks with CRISPR and makes two RNA molecules: one to define the site of the cut and one make the actual cut. These molecules can combine and still get the job done, which is exactly how it is used today. A guide RNA is designed and delivered to the right spot or spots for editing. Early work has uncovered other enzymes that can step in for Cas9, adding to the toolbox.
While this approach has already been used to treat HIV, the biggest concern is that it has the potential to change not only your DNA but also the DNA that could be passed to your future kids. Called a gene drive, this type of editing can permanently fix the DNA of the cell as well as its offspring, creating the ultimate genetically modified organism (GMO).
Although this new approach is very exciting, it is also somewhat scary. Could there be accidents where more than one site of DNA gets changed with unknown consequences? Could we use gene editing to fix hereditary mutations such as those in BRCA? If the genetic defect was fixed in an egg, then presumably the person that egg became would not have an increased risk of breast and ovarian cancer. That could eventually eliminate this defect from the germlines of future generations. But at what cost? The Chinese have already reported initial studies in nonviable human embryos. Do we start making designer babies? To try to get ahead of this train, researchers and ethicists from around the world met in December to start discussions of the bigger issues. It is both scary and exciting and we need to be ready for this brave new world new world.