CRISPR-Cas 9 is a mechanism that can be utilized for efficient and effective genetic engineering. The gene-editing tool was co-invented by Emmanuelle Charpentier and Jennifer Doudna and is set to revolutionise the world of biomedical science and innovation.[1]
The story begins in the 1980s when scientists first observed repetitive DNA sequences in the genomes of bacteria and archaea.[2] The sequences consequently gained the name of CRISPR, Clustered Regularly Interspaces Short Palindromic Repeats. In the early 2000s, their previously unknown purpose was discovered to be part of bacterial defence mechanisms against viruses and other foreign genetic materials. CRISPS regions also contained segments of viral DNA from previous infections known as “spacer sequences”. A continuation in the research on CRISPR, led to a discovery of CRISPR-associated (Cas) proteins, which work in conjunction with the repeats, to recognize and cleave viral DNA based on information stores in the spacer sequences.[3] In 2012, the research group of Emmanuelle Charpentier and Jennifer Doudna, demonstrated how Cas9 endonuclease can precisely cut DNA at locations specified by a guide RNA.[4] The RNA molecule can bind to Cas9 and based on the sequence of the gRNA, can specify the location at which the Cas9 will cute DNA.[5] Cas9 catalyses the cleavage of the double-stranded DNA near the point where the specific genetic sequence to be targeted by the guide RNA meets the repeating, palindromic sequence.[6] Hence, the molecular compound of CRISPR-Cas9, is capable of manipulating genetic material of organisms, leading to its applications in functional genomics, pathway analysis, drug discovery, and disease modelling.[7]
The three main categories of genetic edits performed with CRISPR-Cas9 can be seen with the diagram provided by CIRPSPR therapeutics:
CRISPR-Cas9 has a multitude of revolutionary applications. It can be used to genetically modify embryos, creating new organisms and be injected into the bloodstream of laboratory animals to initiate substantial gene editing in subsets of tissues. Beyond biomedical sciences, it can be used in biotechnology sectors modifying genomes of crop plants, to create more nutritious or pest-resistant food produces. Scientists have also harnessed CRISPR-Cas9 technology to alter the genetic makeup of bacteriophages, which are viruses that attack bacteria. This approach has allowed them to develop strategies for eradicating antibiotic-resistance in bacteria. Additionally, CRISPR-Cas9 systems have been instrumental in generating animal models to study human disease and eliminating HIV from infected cells. In one instance, CRISPR-Cas9 was employed in a mouse model of a human disease, successfully correcting a genetic error, resulting in the clinical rescue of the diseased mice.[8]
However, having a mechanism capable of quick and precise genetic engineering, brings forth grounds for ethical concern and considerations. In 2015, groups of scientists including the founder Doudna wanted to restrain the use of CRISPR-Cas9 in humans, preoccupied with the potential ethical implications of human gene editing. In the wrong hands, a device like this could lead to the immoral creation of designer babies or even biological weapons. However, coming from a different point of view, some scientists wanted to utilise CRISPR-Cas9 to its full potential, deeming that withholding it would be unethical, not alleviating the suffering of many people.[9]
In 2018, He Jiankui a Chinese scientist created a first set of genetically modified babies, or so called “designer babies” using CRISPR-Cas9. He altered the CCR5 gene in human embryos, hoping to provide immunity to HIV.[10] However, doing so without the knowledge of any authorities landed him in prison for 3 years. He announced the birth of twins Lula and Nana, through a video filmed by Associated Press, receiving severe backlash from the scientific community, due to his decision to experiment on human embryos without taking into account the full repercussions and side effects of using the genetic-editing device. The danger with directly editing the genome of embryos, is that any genetic changes have the chance to be passed onto future generations, creating a lasting effect on the human race.
It is undoubtedly certain that technologies such as CRISPR-Cas9 will continue to develop. The introduction of genetic engineering is inevitable with the development of our society. For instance, back in 2015 Zhnag and colleagues proposed the exchange of Cas9 to Cpf-1, claiming that the nuclease paired with CRISPR offers many advantages over Cas9. However, it is important to consider and evaluate the dangers of using genetic engineering tools and impose strict ethical regulations to prevents their manipulation for malicious reasons.
Article written by: Olga Kryl
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References: [1] https://crisprtx.com/gene-editing/crispr-cas9 [2] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5847661/ [3] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8036902/ [4] https://crisprtx.com/gene-editing/crispr-cas9#:~:text=CRISPR%2FCas9%20edits%20genes%20by,revolutionary%20technology%20into%20transformative%20therapies. [5] https://crisprtx.com/gene-editing/crispr-cas9#:~:text=CRISPR%2FCas9%20edits%20genes%20by,revolutionary%20technology%20into%20transformative%20therapies. [6] https://www.britannica.com/science/gene-editing [7]https://www.synthego.com/learn/crispr#:~:text=CRISPR%20gene%20knockout&text=This%20is%20known%20as%20a,and%20screening%2C%20and%20disease%20modeling. [8] https://www.britannica.com/science/gene-editing/Applications-and-controversies [9] https://www.britannica.com/science/gene-editing/Applications-and-controversies [10] https://theconversation.com/did-he-jiankui-make-people-better-documentary-spurs-a-new-look-at-the-case-of-the-first-gene-edited-babies-196714#:~:text=He%20used%20CRISPR%20to%20alter,three%20children%20with%20altered%20DNA.
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