Science and Technology

Long Read: CRISPR – a Molecular Toolbox for Scientific Wizards

Article by Isaac Parr March 3, 2018

Photo by Sebastien Gabriel on Unsplash

A new advancement has taken the targeted editing of human genes from the realms of science fiction into science fact. CRISPR, which stands for Clustered Regularly Interspaced Short Palindromic Repeats, may sound complex but its mechanism is simple.

CRISPR gives scientists a revolutionary genetic tool box to edit genes with. It is cheaper and more predictable than other methods and has numerous applications from GMO crops to eradicating human genetic disorders. Editing the source code of life has never been cheaper and simpler.

What is CRISPR/CAS?

CRISPR/CAS was originally part of the prokaryotic (single-celled organisms, such as bacteria) immune system as a defence mechanism. The organism would fend off invasion by foreign agents trying to infect and destroy it, or hijack it to replicate itself. The CRISPR/CAS system recognises the incoming foreign DNA and releases CAS enzymes that work to destroy it so, protecting the organism from harm.

The CAS enzymes work like a pair of ‘genetic scissors’, cleaving the DNA at specific points. This precise cutting action can be leveraged to edit genes, which is what scientists are now using CRISPR for. Once the DNA has been cut the cell will recognise it as damaged and attempt to repair it, so when this is happening it is possible for us to insert new sections of coding DNA.

What can CRISPR do?

The HIV Virus is responsible for causing AIDS. The virus inserts its DNA into the human genome which disrupts the human immune system, increasing susceptibility to infection. CRISPR has shown promise in being able to locate and remove sections of HIV DNA. However, the virus can maintain a latent state which makes it much harder to find infected tissues when no symptoms are shown. More work is needed to model latent HIV infections in order to combat the disease effectively.

There has been some preliminary research done to investigate the ability to remove blindness causing genes. So far scientists have successfully removed the gene in mice which causes retinitis pigmentosa, the progressive degeneration of rod cells ultimately leading to blindness.

CRISPR is hugely valuable in the area of genetic research. We currently have little idea what 98% of DNA does. Moreover, this huge part of DNA  has been termed ‘junk DNA’ because it has no discernible function and in particular, does not code for any proteins. Why do we have it then? The answer may lie in the world of epigenetics, the interactions between DNA and accessory molecules which act like switches, turning sections of DNA on and off. By using CRISPR to edit this junk DNA we could change the way other molecules interact with it and possibly discover deactivated coding elements which may give further insight into evolutionary genetics.

Fighting genetic diseases

CRISPR technology has the potential to eradicate certain genetic diseases from the population and make them non-inheritable to the future generation. Not only would this mean a greater quality of life for those who would otherwise be affected by a genetic disorder but a lower burden on an already stretched social healthcare system.

In the short term, CRISPR can be used to study diseases with a more targeted approach. Genes can be manipulated in a lab setting to examine different mutations and the effects they have. A greater understanding of disease mechanisms will allow for better therapies to be created.

In the mid term, CRISPR can be used to edit the genes of stem cells. This could be done for multiple reasons. Increasing biotic factor production in the case burn wounds would increase the rate of skin replenishment and decrease inflammation. Genes can also be edited to make stem cell tissues more genetically similar to their intended target which would reduce autoimmune rejection. In the long term, with the right approval and oversight in place, it may be possible to treat at risk embryos to remove genetic disorders such as cystic fibrosis and sickle cell anaemia.

Current methods of introducing foreign DNA are hugely complicated, expensive, and yield limited success

However editing embryonic DNA has its risks. The new DNA has to be delivered by a viral vector which essentially turns the cell into a CRISPR production line for the new DNA. There are concerns over the possible long-term effects of hijacking a biological system in this way. Some of the material being introduced into the cells is bacteria based. This could possibly trigger an immune response and may result in the destruction of the cell.

Despite these concerns, there are successful trials taking place which bring hope to millions of people throughout the world. Research in China has already shown promise in curing blood cancer in children though this is in its infancy. This could be the start of a revolution in oncological medicine and help cancer sufferers which till now may not have had any cure in sight.

The toolbox before CRISPR

Surprisingly genetic modification has been going on for thousands of years. The earliest form of which is ‘selective breeding’. It was coined by Darwin later when he proposed his revolutionary Theory of Evolution by Natural Selection. One of the most important historical examples of this is the cultivation of maize in the Americas from its wild Zea form Teosinte, without which there would be a struggle to provide food to a growing global population.

An understanding of selective animal breeding has been recorded for a millennium. The effects of selective breeding are very apparent in dogs, both the successes and the failures. Selective breeding has been successful as a rudimentary method of producing organisms with desirable characteristics. However, this method involves the combining of whole genomes, the good, the bad, and the ugly, just to increase the magnitude at which a few traits are expressed.

Modern methods of genetically modifying organisms involve splicing a specific gene or genes into another organism’s DNA. This is most easily done with bacteria but it is possible with other organisms. Current methods of introducing foreign DNA are hugely complicated, expensive, and yield limited success regarding reproduction, survivability, and desirable characteristics.

We can do it! …but should we?

When the subject of genetic editing comes up ethics shows up as well. At the first mention of new genetic editing techniques the response seems to never change: ‘Designer babies’, ‘Playing god’, ‘Cloning’. As much as you may want to have a child prodigy pianist with 12 fingers, a 3 headed dog or a battalion of Stormtroopers (admittedly that would be awesome), the ethical issues are way more nuanced than that.

A new technology like CRISPR may become misunderstood and a legal nightmare to use or research

The main points of conflict surround germline editing. This is when a change you make to an organism will be passed on down the generations. Most people have no issue with editing plants and bacteria, or even providing gene therapy in some cases in humans. At the moment it is more of a question of practicality than ethics. Research is in its infancy, we don’t know all of its applications, we haven’t even made it safe. Above basic safety concerns there remains the question of whether we should because we can?

Thankfully, CRISPR is fairly ineffective in humans at this point, giving enough time to lay down some ethical foundations. However this does not mean human editing won’t be viable in the future. How far should we go? What oversight needs to be in place when we can manipulate human embryos? Is it ethical to rid the world of cystic fibrosis or let people suffer when we have the cure.

Future oversight and guidelines will be greatly influenced by public perception and opinion. The people who make the legal decisions or lobby for legislation often aren’t scientists. This often leads to situations where a new technology like CRISPR may become misunderstood and a legal nightmare to use or research. The same thing has happened with GMOs, nuclear power and vaccination, all caused by ill informed hysteria. It is not entirely the public’s fault though. Scientists are the worst people in the world at public relations (with a few exceptions, we love you Bill Nye). People can’t make critical decisions without the facts, FACT.

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