Denirae Davis

Professor Linda Jemmett

Biology 1610

July 28, 2020

CRISPR: Engineering our Future Through DNA

What if I told you that you could change your eye color without contacts? Your hair color

without dye? Your height without heels? Maybe these seem small and inconsequential, so what

about being able to cure cancer? Or cystic fibrosis? How could we change all of these things?

The answer is simple: CRISPR.

To understand CRISPR you first have to understand DNA. DNA is comprised of two

polypeptide chains made of nucleotide bases of ​adenine (A), cytosine (C), guanine (G), or

thymine (T). These bases match up and form a hydrogen bond, adenine (A) with thymine (T),

and cytosine (C) with guanine (G). The order in which they arrange determines our genes and

acts as an instruction manual for how to make us and everything within our body (Alberts, 2002).

Everything we are is based on our DNA–eye color, hair color, height are all things we

can see–but our genes dictate everything about us down to a cellular level. If we are able to

change our DNA we can change anything we want about ourselves. Though this may sound like

science fiction, science is getting closer and closer to making it a reality through CRISPR.

Clustered regularly interspaced short palindromic repeat, CRISPR, were first seen in ​E.

coli i​ n 1987. Though at the time we didn’t understand genomes as well as we do now, they

noticed the repeating segments of DNA but could make little sense of what it meant. It wasn’t

until the mid-2000’s that researchers realized that between the repeats of DNA matched
segments of viral DNA. While to many of us this doesn’t seem very impressive, these scientists

realized that maybe this was some type of immune response of the bacteria, that somehow they

would incorporate the viral DNA so next time it arrived it would be able to fight it off faster

(​Ishino,2018)​.

Researchers started looking at other bacteria and archaea to see if they also contained

CRISPR and found even more that contained the spacers and repeats. But how did this viral

DNA get into these bacterias’ DNA? Researchers started looking for other similarities in the

bacterial DNA and found that near these CRISPR sections of DNA there were sequences that

appeared in many different bacteria; these sequences were called Cas genes or ​C​RISPR

as​sociated genes. Researchers got to work hypothesizing what these genes might be used for.

They thought that Cas genes might be used for some type of DNA repair, recombination, or

chromosome segregation. Due to their correlation with CRISPR researchers believed Cas genes

were likely the reason behind the regularly interspaced repeats (Ishino, 2018).

Researchers discovered that Cas genes code for the Cas proteins. Cas proteins can be

used like scissors to cut apart DNA. The Cas protein most commonly used with CRISPR is

Cas9– but how does Cas9, or any of the other Cas proteins know where to cut? Obviously Cas

proteins are not indiscriminately cutting apart DNA. The CRISPR/Cas9 system uses tracer or

guide RNA to tell the Cas9 protein where the DNA sequence is supposed to be cut. The guide

RNA works like a mug shot for Cas9. Cas9 reads down the strands of DNA until it comes to the

matching sequence then it basically unzips the DNA and cleaves out the unwanted gene. After

the gene is cut the DNA tries to repair itself–this repair can happen by non-homologous end

joining or homologous directed repair. Scientists have found an alternative to these two methods
in which when you are delivering CRISPR/Cas9 into cells you can also deliver the new piece of

DNA you want to replace the removed portion and the cell’s natural repair mechanism will grab

that newly introduced piece of DNA and add it in for the repair (​Redman, 2016)​.

With this discovery, researchers recognized that CRISPR/Cas9 could be the future of

genetic engineering. There were multiple options for genetic engineering prior to CRISPR, such

as meganucleases, zinc finger nucleases, and TALEN. But since CRISPR/Cas9’s discovery it has

become the prominent form of gene editing due to how simple it is to use–but more importantly

how accurate it is and the overall cost. Since making a single wrong cut in DNA could be

devastating, CRISPR/Cas9’s accuracy is what has really set it ahead of the game (Adli, 2018).

While many likely think of CRISPR/Cas9 as a way to change human genes, its efficiency

doesn’t end with us. Scientists are using CRISPR/Cas9 to solve all sorts of problems. Scientists

are working with CRISPR/Cas9 to come up with alternatives to antibiotics. They are editing

plant and animal genes to make them more resilient and resistant to disease. If you read about

CRISPR/Cas9 trials you can see that there isn't much scientists don't think it can do (Hsu, 2014).

Now that we have sung CRISPR/Cas9’s praises let’s talk about some of its drawbacks.

You can’t talk about editing genes without thinking about the dominoes that will fall after editing

those genes. Which brings us to the ethics of using the CRISPR/Cas9 system, which are the same

ethics for using ​any​ gene-editing system. CRISPR/Cas9 just brought this ethical question to the

forefront because it opened a door that we weren’t sure we would be able to open with the other

forms of genetic engineering.

Some questions we should ask before jumping headfirst into the CRISPR/Cas9 pool are

these: Should we limit what researchers and scientists can do with CRISPR/Cas9? Should we
allow scientists to edit germline cells? Or just somatic cells? Should there be an international

governing body that is in charge of overseeing all CRISPR/Cas9 trials to make sure rules and

regulations are being followed? Basically, how far do you let it go when you feel like you could

go all the way but know you shouldn’t? Some would say we have already gone too far. Multiple

in-human research trials are going on right now for various treatments. There have even been

some tests with unviable embryos. Most scientists agree that we should not be using

CRISPR/Cas9 in embryos due to the lack of consent. So where should the line be drawn? And

what should the consequences be for crossing that line (​Brokowski, 2019)​?
 References

Adli M. (2018). The CRISPR tool kit for genome editing and beyond. ​Nature communications​,

9​(1), 1911. https://doi.org/10.1038/s41467-018-04252-2

Alberts B, Johnson A, Lewis J, et al. Molecular Biology of the Cell. 4th edition. New York:

Garland Science; 2002. The Structure and Function of DNA. Available from:

https://www.ncbi.nlm.nih.gov/books/NBK26821/

Brokowski, C., & Adli, M. (2019). CRISPR Ethics: Moral Considerations for Applications of a

Powerful Tool. ​Journal of molecular biology​, ​431​(1), 88–101.

https://doi.org/10.1016/j.jmb.2018.05.044

Hsu, P. D., Lander, E. S., & Zhang, F. (2014). Development and applications of CRISPR-Cas9

for genome engineering. ​Cell​, ​157​(6), 1262–1278.

https://doi.org/10.1016/j.cell.2014.05.010

Ishino, Yoshizumi, et al. “History of CRISPR-Cas from Encounter with a Mysterious Repeated

Sequence to Genome Editing Technology.” ​Journal of Bacteriology​, American Society for

Microbiology Journals, 1 Apr. 2018, jb.asm.org/content/200/7/e00580-17.

Lino, C. A., Harper, J. C., Carney, J. P., & Timlin, J. A. (2018). Delivering CRISPR: a review of

the challenges and approaches. ​Drug delivery,​ ​25(​ 1), 1234–1257.

https://doi.org/10.1080/10717544.2018.1474964

Redman, M., King, A., Watson, C., & King, D. (2016). What is CRISPR/Cas9?. ​Archives of

disease in childhood. Education and practice edition,​ ​101(​ 4), 213–215.

https://doi.org/10.1136/archdischild-2016-310459