CRISPR Cas systems: Triumphs and Troubles

CRISPR/Cas systems are bacterial immune systems that can be manipulated to revolutionize the medical field or even engineer human embryos to meet the specifications we want them to have. Theoretically, using CRISPR-Cas systems, we can add angel-wings or devil-horns to human embryos. 

CRISPR stands for Clustered Regularly Interspaced Short Palindromic Repeats. Basically, these are gene sequences that bacteria acquire from bacteriophages (viruses that attack bacteria) and make it a part of their genome. This acquisition of the bacteriophage gene is accomplished with the help of Cas (CRISPR-associated) proteins. There are ten Cas proteins: Cas1 to Cas10. When a bacteriophage attacks a bacterium and injects its DNA into the bacterial cell, Cas1 and Cas2 proteins chop up this viral DNA and then, insert fragments of this DNA into a CRISPR locus in the bacterial genome. Now, the bacterial genome has been integrated with genes from its nemesis- the bacteriophage. CRISPR loci of the bacterial genome are regularly being transcribed into crRNA (CRISPR RNA). This crRNA forms a complex with Cas9 protein and this CRISPR/Cas9 complex hunts for bacteriophage DNA that dares to infect the bacterial cell again. If the same bacteriophage attacks the bacterium again, the crRNA recognizes its DNA and the bound Cas9 protein cleaves and destroys the phage DNA, protecting the bacterium from being infected twice by the same virus. 

In 2020, Emmanuelle Charpentier and Jennifer A. Doudna were jointly presented the noble prize in Chemistry for discovering CRISPR/Cas9 genetic scissors. They succeeded in recreating the bacterial CRISPR/Cas9 systems in a test tube, and now, the CRISPR/Cas9 systems can be used to modify plant and animal genome. This has a wide variety of applications. For instance, the CRISPR/Cas9 system can be used to ‘knock out’ genes. Knocking out genes means to inactivate them. Synthetic guide RNAs (sgRNA) produced in labs are analogous to the crRNA produced naturally from CRISPR in bacteria. These sgRNAs are created complementary to the DNA sequence that we want to knock out. Once the sgRNA bound to Cas9 binds that specific DNA sequence, it is cleaved. When the double-stranded DNA tries to repair itself after it has been cleaved, mutations are introduced that inactivates that gene. Knocked out genes are important for studying diseases and finding their cures. For example, we can knock out the insulin-producing gene in mice embryos. These embryos will develop into diabetic mice. Now, we can test different medications for diabetes on these mice and find a treatment for the disease. CRISPR/Cas9 techniques can also be applied for treating diseases in adult humans. Clinical trial to treat cancer has already begun. The first trial was held in China on 28 October 2016; a group of scientists led by the oncologist Lu You attempted to treat lung cancer in a patient by injecting cells modified by the CRISPR/Cas9 technique. Clinical trial of using CRISPR/Cas9 to treat cancer has also been approved in the USA. CRISPR has already been successful in curing thalassemia and sickle cell anemia.  Both thalassemia and sickle cell anemia are inherited blood disorders; thalassemia results in reduced production of hemoglobin and sickle cell anemia results in abnormal sickle-shaped red blood cells instead of the normal biconcave discoid-shaped red blood cells. The symptoms of both these diseases can be alleviated using a treatment called ctx001. First, hematopoietic stem cells are harvested from the patient’s bone marrow. Then, the CRISPR/Cas9 technique is used to knock out the BCL11A gene. This gene is responsible for the production of a transcription factor that suppresses the synthesis of HbF (fetal hemoglobin), which is present from the 10th week of pregnancy till 6 months after birth. Once the BCL11A gene is knocked out, HbF can be produced again by the adult stem cells. Billions of these modified stem cells are then re-infused into the patient’s body where they produce healthy hemoglobin that can increase the hemoglobin levels in thalassemia patients or replace most of the defective hemoglobin in sickle cell anemia patients. 

Although CRISPR as a means of treatment has its merits, it is not without any drawbacks. For the ctx001 treatment described above, chemotherapy is needed to eliminate the patient’s existing bone marrow stem cells so that the genetically modified ones can be infused. Chemotherapy has a lot of side effects, such as, hair loss, reduced fertility, ‘chemo brain’ which can result in reduced focus and concentration, kidney problems, etc. CRISPR technology has also raised many ethical questions. In the future, will CRISPR enable the creation of ‘designer babies’ for specific functions? For example, will it be possible to produce genetically modified embryos specifically designed to be more brutal soldiers? Even though it sounds like fanatical theories from science fiction, CRISPR has made it theoretically possible. Also, creating designer babies using CRISPR is not a thing of the future, but a thing of the past. In 2018, the first genetically modified embryos were created by a Chinese scientist named He Jiankui and two of his associates. The scientist had announced his ‘achievement’ at a conference in Hong Kong after the genetically edited twin sisters, Lulu and Nana, had been born. Jiankui and his associates had been jailed and heavily fined in 2019.  Jiankui had taken eggs from a healthy mother and semen from a father with HIV. He then produced genetically modified embryos and then impregnated the mother using IVF treatment. Jiankui claims that the twins that have been born are immune to HIV. He claims to have modified the gene that codes for the protein CCR5. CCR5 is found on the surface of white blood cells and plays important role in the immune system. HIV attaches itself to the CCR5 protein then enters human cells. A naturally mutated form of CCR5 exists that is immune to HIV. Jiankui claimed to have recreated the mutation in the embryos, thus forming children resistant to HIV.  However, scientists from all over the world have doubted his claim. Scientists are concerned that Jiankui had created mutations to other off-target genes that might raise health problems for children in the future. Moreover, unlike adults who have been treated using CRISPR, the children created by genetic modification will be able to pass on these mutations to any offspring they have in the future.  

Even though CRISPR has the potential to cure diseases that have troubled scientists and medical practitioners for years, it has raised many ethical questions. As the technology advances and makes lives better, it also becomes crucial to impose regulations and maintain them strictly to ensure no boundaries are crossed. Nature must not be disturbed to the degree that we create new mutations and pass them on to the new generation of humans. 

Lana Ahmed

Biochemistry and Microbiology Department

North South University


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