Why CRISPR won’t be ignored, anymore

CRISPR/Cas9 is a novel technology, popularly known as a pair of gene-editing scissors that may be able to alter the DNA of live individuals. Through the use of this tool, physicians may be able to alter the human ‘blueprint’ and affect the expression of genetic traits, to cure or reduce symptoms of genetic conditions and diseases. While the technology is still in development, and is being tested for medical use, understanding how it works is essential in becoming aware of how medical treatment may change in the relatively near future.

“CRISPR/Cas9 is a novel technology, popularly known as a pair of gene-editing scissors that may be able to alter the DNA of live individuals” (who doesn’t love a pair of old, yello, ugly scissors)

The term CRISPR is an acronym for Clustered Regularly Interspaced Short Palindromic Repeats. Short, clustered, interspaced orders of nucleotides exist in many bacterial species’ DNA sequences, and initially posed a mystery to researchers attempting to determine their purpose within the genome. Eventually, research teams identified that the DNA that presents between the interspaced CRISPR segments, called ‘spacers,’ are actually fragments of virus DNA. A bacterium withstanding attack from a virus would have the potential ability to incorporate fragments of the viral DNA into its own genome. This would lend that bacterium the ability to recognize that species of virus in future encounters and destroy them more effectively using Cas9. Cas9 is the enzyme that is able to unwind foreign DNA, screen them for DNA that matches the viral DNA in the bacterium’s genome, and then cleave DNA out if it is found to match. While before, CRISPR/Cas 9 existed only as a type of acquired and adaptive immunity within the bacterial defence system, tools from this process are now being manipulated for use in editing human DNA to affect the manifestation of genomic traits in individuals.

“Cas9 is the enzyme that is able to unwind foreign DNA, screen them for DNA that matches the viral DNA in the bacterium’s genome, and then cleave DNA out if it is found to match.”

What new CRISPR-based technology really functions through is the DNA recognition abilities of CRISPR in combination with the Cas9 protein that is able to cut external DNA. RNA generated from CRISPR DNA guides the Cas9 protein to targeted sites to create double-stranded breaks in DNA. By breaking or cutting DNA in this way, humans are able to ‘edit’ the genome and affect the expression of encoded traits. Understandably, this generates much excitement around the possible ability to remove inherited or de novo mutations in humans that result in disease.

For example, sickle-cell anaemia, a blood-related disorder that affects human haemoglobin and results in blood clotting and severe pain, is a disease that is a model target for CRISPR/Cas 9 treatment. CRISPR could potentially be used to trim out the single gene that causes the disease and replace it with a regularly functioning, non-mutated copy. This could result in a complete reversal of symptoms and constitute a ‘cure’ for the disease. Right now, this CRISPR application, in addition to many others, is being investigated in non-human organisms. If these initial forays into CRISPR treatment go well, the technology could move on to human clinical trials and become medically applicable. With regards to sickle-cell anaemia alone, CRISPR could radically improve the quality of life for millions of people worldwide.

While they hold great potential in theory, unfortunately, actual CRISPR/Cas 9 applications are not as straightforward as the scenario described in regards to fixing sickle-cell anaemia in humans. Reigning in popular excitement about CRISPR and presenting the more complicated realities of its use have constituted a significant problem in public knowledge about the tool. As it stands right now, much of the research and development of CRISPR technology is oriented around increasing the specificity of ‘cuts’ the system makes. CRISPR’s value lies in its ability to edit out very specific, small pieces of DNA that manifest problematically in humans. However, the enzymes and proteins involved are imperfect and have the potential to ‘cut’ at any other unspecified, undesired locations. Despite the increasingly low frequency of these events, these unanticipated snips can cause significant damage to an individual by affecting the expression of other genes and possibly resulting in malignant cancer if cellular growth mechanisms are altered. Optimizing the processes to increase the specificity of edits is essential to CRISPR being adopted as a medical treatment. Treatments that alter cells outside of a patient’s body, and then re-insert them, may be able to mitigate the possibility of CRISPR and Cas9 protein going rogue by screening for unanticipated alterations to patient DNA.

“The enzymes and proteins involved are imperfect and have the potential to ‘cut’ at any other unspecified, undesired locations”

There are also more distant issues with the actual incorporation of CRISPR as an accessible medical treatment in hospitals: because it is expensive, complicated, and requires significantly developed medical infrastructure in order to be conducted, CRISPR technology will likely only be available to the wealthy and privileged. For diseases that predominantly affect individuals in developing countries with less access to capital, CRISPR’s curative power may remain a fantasy.

In all, CRISPR/Cas 9 has high potential for transforming and creating genetic medical care. Continuing to keep an eye on the progression and institutional manifestation of current research will surely be fascinating. Hopefully, the technology will be able to be utilized to its fullest extent to better help the global population become healthier and live more freely.

By:
Corey Orndoff
corndorff@minerva.kgi.edu

Illustrations by:
Kamal Teja
kamal.teja247@gmail.com