Cut and paste is a god send that has saved many of us precious time and effort over the years. It’s become a staple of any computer user’s arsenal but what if I told you this technology could be applied to the blue print of life itself; DNA?
CRISPR is a DNA editing tool used by bacteria to protect themselves against viruses. When viral DNA is detected by the bacteria, it releases two short RNA sequences (RNA is like DNA’s cousin only less robust and shorter lived). These two RNA sequences form a complex with a nuclease called Cas9. Think of nucleases as a pair of biological scissors that can cut DNA. One of these RNA sequences contains a region that is complementary to the viral DNA and is known as the “guide sequence”. This guide sequence binds to the viral gene and brings it in to close proximity with Cas9. Cas9 can then cleave the viral DNA in two, thereby disabling the virus. If nucleases are the scissors, the guide RNA is the dotted line showing you where to cut.
Scientists are currently working on tailoring this “cutting” tool to target the human genome by creating guide RNAs that target specific human genes. For diseases caused by problems with a single gene, such as cystic fibrosis, CRISPR could be used to “cut out” the faulty gene and potentially replace it with a healthy one. Although this is yet to be successfully carried out in humans, one research group has managed to “cut and paste” a gene called NRAMP1, which is associated with increased resistance to the bacteria causing tuberculosis, into cattle. CRISPR was used on cow embryos to cut the cow’s DNA (like in the schematic above) and then the NRAMP1 gene was inserted into the gap (1). 20 calves were born with this additional gene, 11 of which survived to 3 months old and did in fact show increased resistance to tuberculosis. Although these results look promising, only a small number of the embryos edited using CRISPR resulted in successful pregnancies and of the 20 calves born, 9 didn’t survive the treatment. The surviving calves appear to be in good health but there could still be complications further down the line.
As you can see, the potential for CRISPR is huge. As well as the prospect of curing genetic diseases, other exciting experiments have already been carried out including the use of CRISPR to treat HIV (2). Scientists in the USA have used CRISPR to cut the HIV virus out of the cells of infected rats. Their data showed that just two injections containing the CRISPR technology into the tail of the rats resulted in a significant decrease in viral gene expression. This finding could have huge implications on how we treat retro viruses in the future. Retro viruses are a type of virus that insert their DNA into the human genome such as Herpes virus and HIV. In the future, CRISPR could be used to simply erase any viral DNA that managed to infect our cells. To top it all off, CRISPR is also being trialled as a therapy against certain types of cancer.
Although the future of this technique is certainly promising, there are still many hurdles to overcome before CRISPR can be used to treat human diseases. Like any biological molecule, there is always the risk of off target effects and so you could end up cutting a gene that is vital rather than your faulty target gene. It’s also difficult to deliver the technology to living cells without disrupting any of the body’s natural processes. The use of CRISPR however is becoming cheaper, easier and more efficient with each passing day but these advancements create concerns about what else this technology could be used for and whether editing the blue print of life is entirely ethical. Despite all this, I for one can’t wait to see where the field of gene editing heads in the next few years with CRISPR at the forefront of the next scientific revolution.
If you’re still intrigued, here’s a video outlining some of the benefits and pitfalls that a future with CRISPR could entail:
(Point to note: In my opinion at least, some of these possibilities are extremely far fetched and it’s worth remembering that we’re a long way off CRISPR becoming routine practice. I thought it was still important to share what others believe could happen if it does but I’ll let you decide how real you think these possibilities are.)
- Y Gao et al., “Single Cas9 nickase induced generation of NRAMP1 knockin cattle with reduced off-target effects.” Genome Biology (2017) 18:13 doi: 10.1186/s13059-016-1144-4
- R Kaminski et al., “Excision of HIV-1 DNA by gene editing: a proof-of-concept in vivo study.” Gene Therapy (2016) 23, 690–695; doi:10.1038/gt.2016.41