Some genetic diseases are caused by a single fault in a 3 billion letter, DNA sequence. With more of our genetic sequence now understood, should we be editing those genes that don’t work properly, or even using this knowledge to eradicate pest populations? Gene editing tools such as CRISPR hold potential to do these things but, what is it and should we be getting excited just yet?
CRISPR (pronounced ‘crisper’) stands for: Clustered Regularly Interspaced Short Palindromic Repeats. Hold on. This is a controversial gene editing tool and was unveiled in 2013, and posed the ability to eradicate diseases such as Huntington’s and Cystic Fibrosis, where the genetic problem had been identified. It also held the potential for ‘designer babies’, providing the opportunity for parents to choose more beneficial or wanted genes for their offspring. This is mainly why the general public objected to it. Many researchers however, were looking at CRISPR’s potential to remove faulty genes and even it’s application in pest control. So how does it work?
A gene editing tool provides the ability to edit an organism’s DNA. DNA is made up of bases (A,T,C,G), and a group of bases make a gene. One gene can be made from anywhere between 100 – 2 million bases. The really hard bit is knowing what part of the sequence of bases causes the fault. Once this is discovered, a gene editing tool can remove, alter or add to the sequence of bases, correcting the problem. CRISPR uses an enzyme (i.e. nature’s catalysts) called Cas9 to target and chop up the DNA sequence where the fault lies. Chopping the sequence will ‘turn off’ the gene and stop the expression which that particular gene codes for. You can also use this method to add in more bases where they are missing and causing disease as a result. Once the change has been made, in theory, this change will be passed to subsequent cells when they divide and grow. What are some applications?
The obvious target would be diseases caused by genetic mutations or lack required genes. One such target could be cancer. At the start of this year (2018), CancerResearchUK published a blog post about the use of CRISPR against cancer cells. Not all cancers are caused by a genetic fault but some are and as a result, are a target for CRISPR research. If it were known which genes caused cancer directly, people could be tested in early life and have this detrimental gene removed. In theory. Tests have been conducted using CRISPR on embryos to successfully remove heart disease causing genes, and make them resistant to HIV. (It should be noted that these embryos were never implanted into a woman, and were not kept for more than 14 days). CRISPR tests on embryos are granted for those which are not to be grown to full term, a HUGE change in ethical law would be required to test further into embryonic growth.
A study was conducted for the first time in mammals to see if researchers could eliminate pests. CRISPR could be used to ensure certain detrimental genetic mutations are passed to offspring, meaning that after only 2 generations the species could be eradicated. An example of this use could be in the elimination of mosquitoes which carry malaria. The idea is not to introduce an entirely new gene but instead, to use those which naturally occur and cause eventual death or infertility. This technique has been tested on mice at the University of California, but the results were hit and miss, not providing a consistent result each time. Please note, the researchers did not give the mice detrimental genes, instead they gave them ones which would express only white fur, to determine if the method would work. The team found that only female mutated mice were able to pass on the new gene to the offspring, and even then it was only a 73% success rate.
The use of CRISPR has seemingly no known bounds. In 2014, CRISPR was used to cure a disease in an adult mammal. Since then, CRISPR has been used to modify genetic material in human embryos, eliminate HIV in mice, and even improve agriculture. However, there is still far to go. Last month, two studies were published in the journal NATURE Medicine, identifying problems with the CRISPR process. They had seen that cells edited with CRISPR were missing key anti-cancer mechanisms, obviously increasing the risk of cancer for those cells. Another paper in NATURE Biotechnology, highlighted issues still to overcome, mentioning that we do not yet know the full effects when we change DNA in gene editing. Preventing the removal of, or damage to ‘good’ DNA, is still to be completely investigated. Therefore, the technology holds potential to be amazing and change the lives of many people with genetic disorders. However, there is still far to go and MUCH more research required before CRISPR can be used as a genetic treatment strategy.