CRISPR –The Latest in Genome Editing Technology

Scientists have been dabbling in genome editing for decades, so what’s the big deal about CRISPR?

CRISPR –The Latest in Genome Editing Technology

Scientists have been dabbling in genome editing for decades, so what’s the big deal about CRISPR?

The New Frontier 

“CRISPR” (pronounced “crisper”) stands for Clustered Regularly Interspaced Short Palindromic Repeats, which are the hallmark of a bacterial defence system forming the basis for what is now known as the popular CRISPR-Cas9 genome editing technology. 

CRISPR currently stands at the forefront of gene-editing technology as it allows genomes to be edited with an unrivalled degree of precision, efficiency, and flexibility.  

The new gene-editing tool has facilitated events such as creating monkeys with targeted mutations (which researchers believe could be a stepping-stone to making more realistic models of human diseases) to preventing HIV infection in human cells.   

George Church at Harvard University used CRISPR to simultaneously alter 62 genes in a pig cell, which proceeded to remove all the retroviruses embedded within the pig’s DNA. Previously pig organs intended for transplants into men and women have been bedevilled by retroviruses, which can infect humans. However, Church’s work suggests that it now possible to eradicate them, opening up a potential pathway to xenotransplants (animal organ transplants).               

The landmark of recent CRISPR studies was in April last year when after weeks of speculation, it was finally confirmed that geneticists in China had modified the DNA of human embryos. As detailed in Nature News:

“In the paper, researchers led by Junjiu Huang, a gene-function researcher at Sun Yat-sen University in Guangzhou, tried to head off concerns by using ‘non-viable’ embryos, which cannot result in a live birth, that were obtained from local fertility clinics. The team attempted to modify the gene responsible for β-thalassaemia, a potentially fatal blood disorder, using a gene-editing technique known as CRISPR/Cas9. The researchers say that their results reveal serious obstacles to using the method in medical applications”.

Unfortunately, the outcome from the resulting embryos was far from successful. After applying CRISPR to 86 embryos, 54 of the surviving 71 embryos were genetically tested. Only 28 spliced successfully, and only a fraction of them contained the replacement genetic material.

Additionally, the researchers conducting the experiment found an astounding number of unintended mutations, at which point they decided to put a stop to the experiment. 

Who invented CRISPR?

CRISPR is actually found in a wide range of bacteria and is a naturally-occurring ancient defence mechanism. It was in the 1980’s when scientists initially observed a strange pattern in some bacterial genomes. Their observations concluded that one DNA sequence would be repeated over and over again and was interspersed with unique sequences embedded in between the repeats.

Scientists were left perplexed until they realised the unique sequences in between the repeats matched the DNA of viruses – in particular viruses that prey on bacteria. It became apparent that CRISPR is one part of the bacteria’s immune system, which stores remnants of dangerous viruses so as to be able to recognise when they next attack.  

The second part of the defence mechanism is set of enzymes called Cas (CRISPR-associated proteins), which hold the ability to precisely snip DNA whilst simultaneously slicing any invading viruses. Genes that form the encoding for Cas are always conveniently located somewhere neighbouring to CRISPR sequences.    


So, Cas9 is an enzyme that snips DNA, and CRISPR is a collection of DNA sequences that tells Cas9 exactly where to snip.

Source: CRISPR

The Ethical Implications

Marcy Darnovsky of the advocacy group, Centre for Genetics and Society believes that when it comes to certain CRISPR experiments such as human-genome editing, “the medical arguments are tenuous and the possible social consequences are grave”.

One major ethical implication is safety. Although the CRISPR tool is precise it also can sometimes be known to cut the wrong section of DNA. However, recent improvements by CRISPR pioneer Feng Zhang (of the Broad Institute at MIT and Harvard) to the tool’s molecular scissors could significantly lower chances of “off-target” editing errors.



Ethical debate also surrounds using the CRISPR technique to “perform what scientists call “germline” editing, manipulating reproductive cells – sperm, eggs or embryos – to spread gene changes to future generations rather than trying, for example, to fix a defect only in one patient’s blood-producing cells and thus cure his or her sickle-cell disease”.

While some scientists are embracing the possibility of gene-editing tools harnessing the ability to remove damaging inherited conditions such as Huntington’s disease or Tay-Sachs from developing in future generations. Others however, warn of the dangers inherent in the process and question the ethics involved.

According to John Holdren of the White House Office of Science and Technology Policy, germline editing for clinical use (i.e. pregnancy) “is a line that should not be crossed at this time”. Francis Collins, director of the US National Institutes of Health, asserts that individuals participating in research must be able to give fully informed consent. He argues however that despite this, “the individuals whose lives are potentially affected by germline manipulation could extend many generations into the future.” In which case, “they can’t give consent to having their genomes altered.”

What’s your perspective? Let us know your thoughts on the ethical implications surrounding CRISPR gene editing in the comment section below.

Protogen is currently incubating a start-up in the genomics space and working with a number of vendors on commercialising predictive and prescriptive health solutions, which integrate genomic big data and research. Check out what we do here and get in contact at info@protogen.com.au or +61 2 8572 4700 for more information

 
CRISPR –The Latest in Genome Editing Technology

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CRISPR –The Latest in Genome Editing Technology

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