A CRISPR Future by Angela Rieck

CRISPR is one of the most important scientific inventions that you may not have heard of. No, it is not one of those great drawers in a refrigerator that keeps your fruits and vegetables fresh. Instead it is one of the most significant breakthroughs in our time. It could eventually cure genetic diseases, cancer, viral infections, and end the organ transplant shortage.

CRISPR (Clusters of Regularly Interspaced Short Palindromic Repeats) is highly technical, I was only able to get a modicum of understanding by reviewing an explanation intended for 14-year olds. But basically, CRISPR is a potential a gene-editing tool that can add, delete, and edit genes in the genome.

While CRISPR DNA is actually billions of years old, it was only recently detected. Scientists discovered that ancient bacteria included DNA segment palindromic repeats separated by “spacers” of DNA, the latter didn’t seem to apply to the bacteria’s genetic structure. Scientists soon realized that these “spacers” were snippets of DNA from previous viral invaders. (A quick explanation, viruses invade our healthy cells and use the fuel from our cells to reproduce and ultimately destroy healthy cells.) These “spacers” allowed the cell to create RNA which matched a snippet of the original viral invader’s DNA. The “spacer” DNA helped it recognize the virus, create an RNA with a protein called Cas 9 to snip the virus from the cell.

Jennifer Doudna, PhD and Emmanuelle Charpentier, PhD were awarded the Nobel Prize in Chemistry for the discovery of CRISPR and the Cas 9 protein.

Why is this so important? Scientists have known for some time how to repair a genetic defect. However, they haven’t been able to deliver the corrected gene to the appropriate genetic location. And that is not all. After the correct location is found, the DNA must then be “broken” and replaced with the corrected genetic structure (through RNA). The DNA can then repair itself with the corrected genetic material. Before CRISPR, there was no mechanism for finding the proper location and replacing it with the corrected gene. Scientists had to hope the corrected gene would attach to the correct sequence which is about a 1-in-25,000 chance. Not good odds.

But CRISPR and Cas 9 have changed those odds. Cas 9 is an RNA programmable protein that can find, snip, and replace the DNA at the matched DNA sequence. Operationally, the cell uses the RNA to guide the Cas9 protein to the “spacers” that sit next to the desired DNA. The protein then “cuts” the DNA sequence that needs to be modified and replaces it with the correct genetic sequence.

Wow.

That is the holy grail of gene therapy.

The applications are staggering. In 2019, researchers tested the technology on a patient with sickle cell anemia. (Sickle cell anemia is a hereditary disease found primarily in people whose ancestors lived in malaria-friendly climates. A single inherited sickle cell gene improves resistance to malaria; but two sickle cell mutations result in sickle cell anemia, which is a deadly disease requiring frequent medical intervention.) A bone-marrow transplant was required to inject the corrected gene; but to date, she has been “cured.”

CRISPR has already been successful in treating some types of leukemia. There are some FDA approved bone and blood cancer treatments that relied on CRISPR to “reset” cancerous cells back into healthy cells. Recently, a laboratory study using CRISPR was able to change cancerous muscle cells back to noncancerous muscle cells.

Other genetic diseases that are being investigated with CRISPR technology are Huntington’s, Ducheme muscular dystrophy, childhood blindness, and inflammation in chronic pain conditions. CRISPR solutions are being studied for HIV, Zika, Lyme and Malaria.

A start-up company is changing the genetic sequence of pigs’ organs to enable them to be a viable substitute for human organs. These genetic changes are designed to prevent our immune systems from rejecting the implanted organs. If successful, pig’s organs could be transplanted into humans and people would no longer die while waiting for an organ transplant.

As with any breakthrough technology there are serious concerns. To date, the CRISPR technique can only correct 50-80% of the cells. Scientists cannot predict what will happen when some cells are corrected and others are not. In addition, there is the possibility that the Cas 9 protein will cut the DNA at the wrong location. The unforeseen consequences are considerable, after all a technology that is so powerful can also be very dangerous.

The biggest concern with ethicists is the potential experimentation on human embryos. CRISPR could be an ideal solution for eradicating genetic diseases such as sickle cell anemia, Downs syndrome, congenital blindness, and Tay Sachs in the embryonic stage. While those are admirable applications, there are others that are not. China reported that they already done an unspecified embryo change in a set of twins.

So look for rapid advances in medicine from this technology. Hopefully, managing this potentially life changing technology with its dark underside will not become a “cutting edge” crisis.

Angela Rieck, a Caroline County native, received her PhD in Mathematical Psychology from the University of Maryland and worked as a scientist at Bell Labs, and other high-tech companies in New Jersey before retiring as a corporate executive. Angela and her dogs divide their time between St Michaels and Key West Florida. Her daughter lives and works in New York City.