On arranging the living organisms in a hierarchical manner according to their level of body organisation, we know that the higher organisms have a better defence mechanism against fighting the pathogens and diseases in such a way that when the organism is infected, its body undergoes certain mutations in its genes.

The body develops a memory mechanism so that it is not affected by a similar disease again. However, a fascinating discovery suggested that a similar mechanism is undergone in prokaryotes. Bacteria develop an adaptive immune system which acts as a defence mechanism against viruses (bacteriophage). This is called as CRISPR (Clustered Regularly Interspaced Short Palindromic Sequence) which is a super beneficial discovery adopted in biotechnology for the modification of plant and animal cell. This technology has grown famous and has drawn public attention after its serendipitous discovery and multiple experiments conducted by Jennifer Doudna and Emmanuel Charpentier who received Nobel Prize in Chemistry in 2020. It is a favourable procedure due to cell conditions and provides specific functions. 

NATURAL PATHWAY OF CRISPR IN BACTERIA

The invading DNA enters the bacterial cell and gets attached as a spacer in the palindrome sequence (pre crRNA) of the bacteria at the CRISPR locus. It forms a complex along with tracr- RNA and transcribes to form guide-RNA. The Cas -9 protein gets activated on attaching to the guide-RNA and stores as a memory. Further invasion of pathogen DNA is cleaved, mutated and disintegrated by CRISPR – Cas9 complex. CRISP/ Cas9 system helps to tackle the cell from the infecting DNA of the pathogen(virus). Cas 9 is the RNA dependent endonucleases or restriction enzymes that act on the DNA of the virus to cut them and deactivate them before they enter the genome of the bacteria.

CANCER TREATMENT IN THEORY

It has been proved to be more than a gene-editing tool. Studies are being done to prove its efficiency in various aspects and one of which is curing of diseases with a genetic cause, especially cancer. CRISPR mechanism is used to tackle the oncogenic viruses by doing a cut and paste job and putting a genetic band-aid over it. One way of viewing it is by editing cells and making them resistant against cancer by increasing its immunity. As cancerous cells lead to ostomy, it needs to be rectified and treated on time. For this, you can find out about ostomy care from Byram Healthcare. Studies have been conducted on its application by either directly introducing it on the cells of a cancer patient or as prevention by introducing it in the embryonic stage of normal people. This mechanism can be carried out through the conventional process of Cas 9 complex. However, new researches have suggested its use similar to stem cell therapy in theory. Stem cell engineering has defined the use of stem cells which can be modified into any type of cell by allowing it to undergo the specific function carried out by the required cell. CRISPR – Cas 9 can be modified where we can change the target of this complex from a DNA sequence to a gene and control its activation. We can change the purpose of the cell and assign it a particular function to be carried out which certainly can be providing immunity against cancer. 

EXPERIMENTS CONDUCTED ON CANCER TREATMENT

In reality, this process is not as easy as it sounds. The most challenging part is to identify the palindrome sequence. The other difficulty is to manufacture the oncogenic viruses and wait for a series of experiments to be conducted. This can be very inefficient for patients who are terminally ill as they do not have a long time to wait. According to an article published by Nature in 2018, scientists used electrical stimulation, not viruses, to ferry genetic material into the cell nucleus. This is called “electroporation,” and it shortens the process to a few weeks. CRISPR has the potential to revolutionize cancer therapy, chiefly in the realm of immunotherapy. In cancer immunotherapy, the treatment of genetically engineered immune cells called T cells to find and kill cancer cells, as if they were a cold virus. The main motto of this technology is to prevent the tedious procedure of radiation and chemotherapy which has its side- effects and provide hope during extreme cases where even the surgery is a failure. Dr. Alexander Marson of UCSF, senior author on the electroporation study, suggested that we may get an answer about CRISPR’s cancer applications rather soon. His team hopes to treat siblings who have an autoimmune disease so rare that it lacks a name. These patients’ T cells have already been corrected using the non-viral gene-targeting method in the lab. The goal is to transfer corrected cells back into the children to treat their disease. Important work remains ahead to develop clinical-grade corrected cells, test their safety and seek regulatory approval, Marson told Live Science (renowned magazine). Introduction of new cells called Chimeric antigen receptor T-cells (CAR T cells) is technology to modify T- cells to recognize cancer cells in order to more effectively target and destroy them. Scientists harvest T cells from people, genetically alter them, then infuse the resulting CAR-T cells into patients to attack their tumors. CAR-T cells can be either derived from T cells in a patient’s own blood (autologous) or derived from the T cells of another healthy donor. Researches confirmed the study of cancer of type multiple myeloma and sarcoma in the University of Pennsylvania in Philadelphia where CRISPR technology has been used to treat these patients. They came with a conclusion that only in the presence of ADPTC cells (immunosuppressive cells) can the CRISPR technology be carried out.  While there are common mutations that turn on oncogenes and turn off tumor suppressor genes, the number of targetable genetic drivers of tumor initiation and progression is low, making cancer an extremely difficult disease to fully treat without recurrence. To attempt to narrow down the list of potential cancer-causing genes, researchers are using CRISPR screens to identify new and relevant cancer targets. This another potential use of CRISPR in cancer treatment. The main goal is to enhance the function of memory T-cells and helper T- cells to fight against the oncogenes from causing mutations.

CONCLUSION

 Coming to the title of my article……. How far has CRISPR progressed in Cancer Treatment? Well, the gist is that we have come a long way in mitigating the risk factor, it has been a total success. We have multiple theories and in vitro samples which proves a high potential for further developments and efficient use of CRISPR in treating human diseases.