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Tag: CRISPR

Mosquitoes wiped out by CRISPR–Cas9 gene drive

Up to what extremes are we willing to take in order to ensure the survival of our species? Mosquitoes may be tiny and insignificant. But, they are one of the deadliest ectoparasites that ever lived. They do not just feed on our blood. They could even leave us with a gift – like a “Pandora’s box” of dreadful diseases. Thus, we took a long stride. We armed ourselves with various weapons against these obnoxious flying “bloodsuckers“. And recently, researchers from Imperial College London came up with a novel strategy aimed at destroying them at their molecular level — by hacking their DNA with CRISPR technology.

 

 

 

Little flies

mosquitoes
Mosquitoes belong to the Order Diptera of Class Insecta

 

Mosquitoes are winged insects that belong to the Order Diptera. Their name means “little fly“. They have slender bodies, a pair of wings, three pairs of legs, a proboscis, and a pair of feathery antennae. Their life stages include egg, larva, pupa, and adult. Gravid female lays eggs on the water surface. Larvae hatch from the eggs and grow into pupae. Pupae, also called wrigglers, develop further and then emerge from the water as adults.  Adult males feed on nectar whereas adult females feed on blood. The females have specialized proboscis that they use to puncture the skin of their host and to suck blood.

 

 

 

Pandora’s box

Female mosquitoes feed on the blood because they need nutrients from the blood when they produce eggs. Blood does not coagulate in their proboscis because of the presence of anticoagulants in their saliva. They inject saliva into the skin of the host. Inopportunely, the saliva also serves as the main route by which mosquitoes introduce pathogens into the host’s bloodstream. Some of the mosquito-borne diseases include yellow fever, dengue fever, chikungunya, malaria, lymphatic filariasis, tularemia, and Zika disease.

 

 

 

CRISPR, the game changer

CRISPR-Cas9 – a customizable tool that cuts and inserts small pieces of DNA at specific areas along a DNA strand. (Credit: Ernesto del Aguila III, National Human Genome Research Institute, NIH)

 

Scientists from Imperial College London had a breakthrough when they used CRISPR technology for a gene drive to completely wipe out a population of mosquitoes grown inside the lab.1

 

Short for clustered regularly interspaced short palindromic repeats, CRISPR is a gene-editing tool that scientists use to splice specific DNA targets and then replace them with a DNA that would yield the desired outcome.2

 

The researchers used CRISPR–Cas9 gene drive to suppress the population of caged Anopheles gambiae mosquitoes (human malarial vector). They modified the gene responsible for determining sex in male mosquitoes and turned the male gene dominant. Then, they added these “hacked’ mosquitoes to a caged population of unaltered male and female mosquitoes. The next generations of females could no longer lay eggs and could not bite. And by the eight generation, the population had no longer had females.3

 

 

Wiping out mosquitoes

Not all species of mosquitoes act as our straight foes. Thousands of mosquito species do not serve as vectors of diseases. Only a few hundreds (about 200) of them transmit human pathogens (e.g. Aedes aegypti, Anopheles spp.). Unfortunately, these few hundreds carry viruses, bacteria, protozoans, and helminthes that can cause serious, even fatal, diseases. Furthermore, current methods to eradicate them, e.g. spraying or fogging using insecticides, proved less ineffective since they developed resistance to such insecticides. Thus, the CRISPR technology could prove useful in this regard. However, the question remains: What will happen when these mosquitoes are completely eradicated from the face of the earth?

 

Obviously, humans reap directly the benefit of eradicating mosquito-borne diseases. However, it might also lead to an irrevocable ecological impact we could regret. Particularly in the food chain, loss of certain mosquito species could lead to the insufficiency of food for insectivores, such as birds and fish.  And over time, humans might eventually suffer as well from this jarring food-chain disturbance.

 

Mosquitoes have lived for so many million years. Do we have the right intent and purpose to deny them the right to live side by side with us? Could it be that we are in the verge of desperation? Definitely, we possess a powerful tool in our hands by the advent of CRISPR technology. However, what good of a purpose would it be if we use it solely for our own good?

 

 

— written by Maria Victoria Gonzaga

 

 

References:

1 Kyrou, K., Hammond, A. M., Galizi, R., Kranjc, N., Burt, A., Beaghton, A.K., Nolan, T. & Crisanti, A. (2018). A CRISPR–Cas9 gene drive targeting doublesex causes complete population suppression in caged Anopheles gambiae mosquitoes. Nature Biotechnology. Retrieved from https://www.nature.com/articles/nbt.4245
2 Gonzaga, M. V. (2018). CRISPR caused gene damage? Rise and pitfall of the gene-editor. Biology-Online.org. Retrieved from

CRISPR caused gene damage? Rise and pitfall of the gene-editor


3 Houser, K. (2018 Sept. 25). SCIENTISTS WIPED OUT A MOSQUITO POPULATION BY HACKING THEIR DNA WITH CRISPR. Futurism.com. Retrieved from https://futurism.com/the-byte/gene-drive-mosquitos-crispr?fbclid=IwAR13KtvXDAeOnL7tjTIOL0-E4Q59HHquKev73tiBfirxypfcNkxeZUNEi7A

CRISPR caused gene damage? Rise and pitfall of the gene-editor

CRISPR as a gene editing tool made a prodigious leap forward in science. In 2015, it was heralded as Science’s 2015 Breakthrough of the Year.1 It stymied other impressive contenders like Ebola vaccine. It supersedes other gene-editing predecessors, such as TALENs (transcription activator-like effector nucleases) and ZFNs (zinc finger nucleases). Unlike these two, CRISPR does not need a custom protein for every targeted DNA sequence. It does, however, require a guide RNA (gRNA). Even so, the process of designing a gRNA is easier and less time-consuming than creating a custom protein. For that, it is favoured over other gene-editing tools.

 

 

The rise of a revolutionary gene-editing tool — CRISPR

CRISPR-Cas9 – a customizable tool that cuts and inserts small pieces of DNA at specific areas along a DNA strand. (Credit: Ernesto del Aguila III, National Human Genome Research Institute, NIH)

 

The discovery of CRISPR was indeed phenomenal. Short for clustered regularly interspaced short palindromic repeats, CRISPR swiftly opened avenues for biological and medical innovations. Initially identified as a family of viral DNA snippets, it was discovered to inherently protect bacteria against re-invading bacteriophages akin to our immune system’s adaptive immunity. This natural gene-editing system in bacteria has two key players: gRNA and Cas9 (CRISPR-associated enzyme). The gRNA finds and binds to specific DNA target. The Cas9 goes where the gRNA is, and then cuts the DNA target, disabling the latter. Now, scientists exploit it as a way to splice specific DNA targets and then replace them with a DNA that would yield the desired outcome. For instance, CRISPR can be used to correct physiological anomalies caused by gene mutations or defective genes.


CRISPR-Cas9 system. (Credit: marius walter, Wikimedia Commons under CC BY-SA 4.0 Int’l license)

 

 

 

CRISPR – a versatile gene-editing tool

CRISPR has been shown to have the potential to slow down the progression of cancers. It can switch off a gene in immune cells. The altered immune cells can be designed to fight cancer. In 2016, US FDA approved the clinical trial study where CRISPR technology would be used to cure patients with cancers. 2 Not only in biology and medicine, the use of CRISPR has also extended to agriculture and animal husbandry. Through it, the genes of crops and livestock can be improved. They can be made more resistant to certain diseases.

 

 

 

CRISPR causing gene damage?

One of the issues raised against CRISPR is ethical concerns. Similar to what was ethically raised against other gene-editing technologies, the concern is chiefly about the notion of bias and “playing God”. What are the standards that will define and permit judgment over a gene to be construed as either “good” or “bad”? But taking aside this issue, there is another issue being hurled against CRISPR. Marked of recent as “breaking news”, a study published in Nature warned about the possible pathogenic consequences of CRISPR when the researchers identified on-target mutagenesis in the form of large deletions and complex genomic rearrangements at target sites in mitotically active cells of mice and humans.3 This is not the first time that a study questioned the safety of CRISPR technology. In 2017, researchers from Columbia University reported that it led to hundreds of unexpected mutations. Nevertheless, this claim was retracted when they failed to replicate their results.4

 

 

CRISPR as a gene-editing tool wields so much potential beyond one can imagine. It is easy to use, feasible, and far-reaching. One can expect that issues would come along the way, and thus slow down its fast-paced utilization in different fields. It is a no-nonsense stumbling block for we belong in a community that moves forward through social discourse fueled by scientific nosiness and reasoning. Probing the dangers of CRISPR should be as extensive as exploring its benefits. We must be not too quick to adulate without first bringing out in the open its risks — especially ones that are as crucial as mutations and gene damage.

 

 

— written by Maria Victoria Gonzaga

 

 

References:

1 Science News Staff. (2015). And Science’s 2015 Breakthrough of the Year is…

ScienceMag.org. Retrieved from http://www.sciencemag.org/news/2015/12/and-science-s-2015-breakthrough-year

2 Reardon, S. (2016). First CRISPR clinical trial gets green light from US panel. Retrieved from

https://www.nature.com/news/first-crispr-clinical-trial-gets-green-light-from-us-panel-1.20137

3 Kosicki, M., Tomberg, K. & Bradley, A. (2018 July 16). Repair of double-strand breaks induced by CRISPR–Cas9 leads to large deletions and complex rearrangements. Nature Biotechnology. https://doi.org/10.1038/nbt.4192

4 Dockrill, P. (2018 July 16). BREAKING: CRISPR Could Be Causing Extensive Mutations And Genetic Damage After All. ScienceAlert.com. Retrieved from https://www.sciencealert.com/crispr-editing-causes-frequent-extensive-mutations-genetic-damage-target-deletion-site