The CRISPR-Cas9 system has revolutionized modern science and the things which were once perceived as science fiction is now potential reality. Precisely modifying the DNA is the holy grail of science and the availability of the CRISPR-Cas9 system to execute this, has opened up the doors to a future of utilizing this technology to eradicate diseases, especially hereditary diseases like sickle cell anemia, cystic fibrosis, beta thalassemia, Huntington’s and Duchenne’s muscular dystrophy, to agricultural applications, such as improving crop yield and resistance to pests, and even eradicating certain pests such as malaria-carrying mosquitoes.

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The remarkable aspect of the CRISPR-Cas9 gene editing system is that it was conceptualized from what happens in the nature in bacteria. The CRISPR is part of the adaptive immune response in bacteria- bacteria capture snippets (images) of DNA from invading foreign viruses and use them to create DNA segments known as CRISPR arrays (which get stored in the memory bank of the bacteria). The CRISPR arrays allow the bacteria to “remember” the viruses (or closely related ones). If the viruses attack again, as part of a defense mechanism the bacteria produce RNA segments from the CRISPR arrays to target the viruses’ DNA. The bacteria then use Cas9 or a similar enzyme to cut the DNA apart, which disables the virus. Similarly, in the lab the CRISPR-Cas9 method uses a small guide RNA with a scissor like protein called Cas9 which finds and cuts the faulty DNA sequence at the precise spot. Once the cut occurs the cell completes the editing by using the correct genetic sequence from a piece of the DNA which is also supplied as part of the system. Think of it as a ” find and replace” tool in your word document, but instead of words you are correcting the gene sequences.

The CRISPR-Cas9 system is not only the most precise but also one of the most versatile, inexpensive and fastest and readily available gene editing tools. This raises a lot of ethical concerns like the use to the technology in embryos for instance? Could the controversial birth of the two designer babies in China write the opening paragraph for the next chapter in the history of eugenics? Although the scientist involved claimed that he used the technology to protect the babies from HIV (by disabling the CCR5gene involved in HIV infections) this has shaken up the scientific community by storm as to what the future might hold. We suddenly find ourselves in an era in which science in the wrong hands, could rewrite the gene pool of future generations by altering the human germ line. There is a thin line we cross from therapeutic use of the technology towards misuse for what might seem as a greater good of humanity. Therefore, proper ethical regulations should be in place for the use of the technology strictly for treatment and diagnostic purposes.

Despite a lot of controversy human clinical trials are already underway involving the use of CRISPR in the treatment of various diseases. US scientists are using CRISPR-Cas9 to combat cancer and blood disorders like sickle cell disease in people. In these trials scientists remove some of a person’s cells, edit/ correct the DNA and then inject the cells back in, now hopefully armed to fight disease.

As one of the first of its kind, University of Pennsylvania researchers have given two cancer patients CRISPR Cas9 therapy. One person has multiple myeloma; the other, sarcoma. As part of the clinical trial, both patients received T-cells, a type of white blood cells in the immune system, which were programmed and modified using CRISPR Cas9 to fight cancer cells.

Trials are also under way for two inherited forms of blood disorders- sickle cell disease and beta thalassemia. Both result from defects in the gene for hemoglobin, the oxygen-carrying protein in the red blood cells. As part of the trial, scientists are testing whether CRISPR-Cas9 editing can turn on fetal hemoglobin (which is normally present in the fetus, but not child and adulthood of all humans and helps in increased oxygen absorption in mother’s womb. The fetal hemoglobin seems to be turned on naturally in some patients with these blood disorders alleviating some of their symptoms) for life and ease symptoms in people with the blood disorders.

In another break through, researchers are also set to see how CRISPR/Cas9 gene editing works inside the human body. Leber congenital amaurosis 10 (LCA10) is a type of inherited blindness. Even though they have normal eyes, patients with this type of blindness lack a gene that turns light into signals to the brain that enable sight. The first set of patients to receive the CRISPR therapy are adults who are completely blind. After having some of the gel-like tissue in their eyes removed, patients will have the treatment injected behind their retinas. The hope is that the patients’ DNA will repair itself in a way that restores normal protein function, ultimately fixing their photoreceptor cells and letting them see.

Although CRISPR clinical trials are only in their infancy, the therapy does seem to show tremendous promise, in theory, in the treatment of many diseases if it works and if there are no other “off target” effects from the gene editing process. CRISPR can, at times, inadvertently edit genes that were not intended to be altered leading to cancers. After all we are still trying to manipulate nature. But as they say no risk no reward. The promise of the technology and the fact that it has been vetted thoroughly by scientists around the world, makes it for a compelling case to be tested in humans especially for diseases where all other treatment options have failed. The long-term outcome of the patients undergoing the CRISPR clinical trials is not known yet. Only time will be the judge of success of the CRISPR-Cas9 therapy.

About Author: A PhD qualified cardiovascular research scientist interested in everything science and medicine.