BiologyRosalind Franklin day

CRISPR CAS-9: How a biological enigma lead to today’s most widely used gene editing technology

It started out as an oddity. A sequence of viral DNA in the genome of a bacteria, as out of place as a bull in a china shop. A curious observation led to the latest method for editing genes: CRISPR.

CRISPR (Clustered Regularly Interspaced Short Palindromic Repeats) are sequences of viral DNA found in bacterial genome[1]. They were first discovered in E.coli bacteria over three decades ago, in 1987. Initially, their presence caused a great deal of confusion. What was viral genetic material doing in a bacteria? Later, similar sequences were discovered in several species of archaea.

Eventually, scientists came to realize that CRISPR forms a pivotal part of the bacterial immune system[1]. Bits of DNA from attacking viruses are stored in the form of CRISPR to protect against future attacks by the same pathogen[1]. The Cas-9 (short for CRISPR associated protein-9) protein can recognize virii with the specific DNA sequence and ‘cut’ their genetic material, killing them[1]. CRISPR Cas-9 can be said to act almost as a bacterial ‘vaccine’.

An interesting phenomenon, most researchers concluded. But scientist Jennifer Doudna saw something else: potential for what would become one of the most reliable genetic editing[2] . Doudna’s lab at the University of California at Berkeley collaborated with the lab of Emanuelle Charpentier in France to modify the target DNA sequence the Cas-9 identifies[2]. This meant they had a tool to cut out any DNA sequence they desired by simply changing the target of the Cas-9 endonuclease enzyme.

CRISPR Cas-9 was first used to edit human mammalian cells in 2013, and has since been used for genome editing as well as for epigenetic modifications[2]. An advantage of this method is that it can be used to edit genes on multiple loci simultaneously: a characteristic that cements its role as a crucial tool in biological research[1]. It has enormous potential in the field of cancer research; scientists hope to use CRISPR to eliminate mutations in oncogenes and tumor suppressor genes such as p53 that lead to tumor formation. CRISPR is even being used to combat cardiovascular diseases and neurodegenerative disorders [2].

As with every paradigm shifting scientific discovery, CRISPR Cas-9 comes with a moral dilemma – do we have the authority to edit our own genome? Could we create a race of superhumans? It’s theoretically possible, but also frightening. In 2018, a scientist in China edited human embryos with the purpose of removing the gene that leads to AIDS[3]. Not surprisingly, his actions caused an uproar in the scientific community. It’s clear that the use of CRISPR Cas-9 must be carefully monitored and ethical guidelines must be obeyed.

It’s amazing how a stray sequence of DNA in E.Coli has led to a genome editing technology that could help in saving millions of lives. You might even call it a miracle.

REFERENCES:

[1] History of CRISPR-Cas from Encounter with a Mysterious Repeated Sequence to Genome Editing Technology

Yoshizumi Ishino, Mart Krupovic, Patrick Forterre

Journal of Bacteriology Mar 2018, 200 (7) e00580-17; DOI: 10.1128/JB.00580-17

https://jb.asm.org/content/200/7/e00580-17.full

[2] Alvin Powell, 2018.” Crispr’s breakthrough implications.” The Harvard Gazette

https://news.harvard.edu/gazette/story/2018/05/crispr-pioneer-jennifer-doudna-explains-gene-editing-technology-in-prather-lectures/

[3] Gena Kolata and Pam Bullock. 2018. “Why Are Scientists So Upset About The First Crispr Babies?” The New York Times

https://www.nytimes.com/2018/12/05/health/crispr-gene-editing-embryos.html

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