Scientists genetically edit the innate immune cells using CRISPR-Cas9

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A human body’s biggest line of defense against the pathogens is its own immune system. There are several drugs administered to fight various diseases, but all that these drugs do is enhance the capability of the body’s own immune system.

Scientists are trying to find a way to genetically modify the immune system of a human body, such that it can provide the body with a better defense system. The immune system of a human body may rely on antibody production, but they are the innate immune cells that are present at the frontier. Not only do they fight against foreign invaders, but they also recognize common molecular patterns amongst pathogens.

CRISPR-Cas9 is a gene-editing tool, Cas9 being a scissor-like protein. A UCLA research team has already conducted a successful modification to the DNA of innate immune cells using this gene-editing tool. Their findings were published in a study, “CRISPR-Cas9 Ribonucleoprotein-Mediated Genomic Editing in Mature Primary Innate Immune Cells”.

Injecting Cas9 into the body through a harmless virus to genetically modify the living cells is not a new technique and has been used for quite a while now. It is even used to modify genes within bacterial cells. However, when injected in the body via a harmless virus to alter the genetic structure of innate immune cells for enhancing their efficiency, the cells reacted against the virus and became active. Hence, the procedure failed.

Trying to figure out other ways to administer Cas9 to innate immune cells, scientists decided to make the outer layer of the cells porous by sending electrical pulses through them, beforehand. this caused Cas9 and other surrounding proteins to seep into the cells that were under observations. According to Luke Riggan, one of the authors of the study, mentioned that they optimized the process in a way that not only Cas9 seeped right to the target in the nucleus, but the process got 95% more efficient.

The tests were then carried out on mice. Mice were administered with a viral infection which they were able to fight off very well with the existing gene structure of their immune system. Afterward, their dendritic cells were genetically modified by removing the MyD88 gene. Later when they caught the same virus, their immune system was unable to fight it off, resulting in their death.

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The scientists also took the opportunity to genetically modify the natural killer cells, and know more about how each gene contributes to the cause of the cell in fighting off diseases. If natural killer cells are genetically modified to be more efficient, they can cure cancer and tumors.

This recent discovery can lead to huge advancements in medical sciences, as claimed by O’Sullivan. It can help scientists learn more about each of the genes that plays its role in a body’s immune system. In this way, scientists can learn about the genes which are crucial to the cells. Further tests and studies are being carried out on cells present in the human blood.

Reference

Luke Riggan et al. CRISPR-Cas9 Ribonucleoprotein-Mediated Genomic Editing in Mature Primary Innate Immune Cells, Cell Reports (2020). DOI: 10.1016/j.celrep.2020.107651

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