Genius genes: How CRISPR is revolutionising DNA manipulation

From preventing the next Zika virus to saving endangered species: do the benefits of DNA manipulation outweigh its potential dangers? Medical genetics PhD student Chloe Warren untangles the arguments

DNA manipulation has seen a revolution in the last few years due to the advent of CRISPR/Cas9 technology – otherwise known as gene editing.

The field itself is not new; scientists have been manipulating organisms’ DNA sequences in research labs worldwide for decades to investigate how genes work.

Even CRISPR itself, which stands for ‘clustered regularly interspaced short palindromic repeat’ – a pattern found in DNA sequences – was first identified in bacteria more than 30 years ago. But it wasn’t until the early 2000s that its significance was realised.

Now CRISPR/Cas9 brings groundbreaking potential to the field of biotechnology, allowing scientists to precisely edit genes.

The manipulation of DNA now takes days as opposed to years and experimental costs have drastically reduced

As a result, the manipulation of DNA now takes days as opposed to years and experimental costs have drastically reduced. Where scientists could previously only modify DNA of a select group of model organisms, they are yet to identify a species for which CRISPR gene editing is not possible.

Although research into the intricacies of the process have only just begun, CRISPR even allows the genetic editing of human embryos. This could see the elimination of genetic disease or even the risk of inherited cancers or Alzheimer’s disease.

‘Designer babies’

Despite the numerous successful applications of DNA modification, it’s unsurprising that the reception of such technologies has been mixed throughout their history.

There are unresolved concerns about the effect of GM crops on biodiversity, and as a result, no commercial GM crops are currently grown in the UK. Gene therapy can also have a number of side effects, including infection or even cancer. And now that we are capable of editing genes of human embryos, this list of ethical and medical concerns is growing rapidly.

What could a potential parent class as an unwanted genetic trait for their offspring – a debilitating disease, dwarfism, a chronic pain condition, deafness or blindness?

The concept of ‘designer babies’, while now technically a possibility, is still far from becoming a reality in this country. Although a British fertility research lab was recently granted permission to edit genes of human embryos, the scientists have to adhere to strict protocols wherein the embryos must be destroyed within seven days.

But on the global scale, technology may be moving faster than it can be regulated. In fact, some scientists are calling for a moratorium on gene editing technologies to allow regulations to be properly discussed.

Although ethical considerations should be paramount in the approval of new biotechnologies, it cannot be denied that the advances brought to the field by CRISPR/ Cas9 are enticing.

A huge range of threats to global health and prosperity could be moderated with the advent of these technologies. Malnutrition, crop and livestock loss due to climate change, mosquito-borne viruses, such as Zika, antibiotic-resistance, genetic disease, cancer, HIV/AIDs, fertility and the extinction of endangered species could all be mitigated with gene editing. While it remains unclear what these technologies might deliver, scientists around the world, including me, wait with anticipation to find out.


How CRISPR works

When bacteria survive a viral invasion (the bacterial equivalent of a cold or flu), the viral DNA is incorporated into the DNA of the bacterium under attack, forming the intriguing CRISPR patterns. Bacteria can use these collected chunks of invader DNA to arm their patrolling defensive proteins (e.g. Cas9) with viral ‘mugshots’ (credit to Eugene Koonin for this metaphor). If the defensive proteins find any viral DNA that matches its invader mugshot, it will chop it up and destroy it, protecting the cell from the virus. Scientists have now worked out how to hijack these defensive proteins: by arming them with a synthetic DNA sequence matching that which they wish to edit, the protein can locate and chop out the target sequence, replacing it with an altered version. This is no mean feat when we consider that there are three billion bases of DNA in a single human cell.


Image: McGovern Institute for Brain Research