There is an increase in the buzzing mentions of CRISPR (Clustered regularly interspaced short palindromic repeats)—a gene-editing tool developed by scientists that recently underwent a significant trial. A lot of the potential applications of CRISPR may sound superficial and fantastical and are made far too early in the life of the field’s research. Publications frequently carry pieces on the revival of extinct species or cures for cancer, the medical holy grail. This sustained flow of CRISPR publicity has made it the subject of curiosity and conversation beyond the scientific and research-led world. Why is it all the rage in the world of genetics? What possibilities does it hold? Let’s dive in to understand where CRISPR stands today.
Highlights
- Why is CRISPR trending in the world of genetics? A landmark trial on CRISPR, a gene-editing technology, has proven that it is possible to alter or ‘edit’ the genes in our body to treat certain conditions as well as diseases stemming from them within our bodies,
- There is immense buzz around CRISPR and the possibilities it could offer. However, research in the area is still nascent,
- CRISPR research currently stands at a point of throwing up more questions than providing answers. Concerns around CRISPR include, but are not limited to long-term impact and effectiveness, and adverse reactions that particular or wide sets of conditions may have to CRISPR. A lack of general safety standards or best practices is yet to be established for the method of treatment.
What is CRISPR and how does it work?
Conversationally referred to as CRISPR and formally as CRISPR-Cas9, it is a toolkit operating at a molecular level that can accurately alter the contents of DNA—the human body’s functional, genetic life code. The concept and mechanism for CRISPR are also found in bacteria, from which it was inspired. Its function in bacteria was to safeguard microbes from virus attacks. The mechanism behind CRISPR has two parts: RNA, and Cas9, with the former being the guiding light to the latter. RNA is chemically related to DNA, while Cas9 is labelled as ‘molecular scissors’. RNA guides the Cas9 to a site where it makes a corrective cut across the DNA.
- This cutting of a gene gives some directions to the results. These can be:
- The gene’s functions are altered or disrupted.
- The cut gene can be removed completely or cut further.
- Specific composition or structural changes to the DNA’s sequence can be made.
- A new gene can be used to replace the cut part of a gene.
CRISPR-Cas9, thus, with its precision, can open up a breadth of possibilities for genes that carry or are conducive to poor health conditions.
The landmark clinical-trial CRISPR result
Awarded a Nobel Prize in 2020, the possibilities of CRISPR, a gene-editing technology, stem from its impact on treating a protein misfolding disorder and a rare progressive condition – transthyretin amyloidosis. In the landmark trial, two things were clear. The first is that CRISPR and its gene-editing capabilities can treat conditions in the human body. The second, that of the six patients the trial took place on, the side effects were mild and sparse. These results were published in the New England Journal of Medicine and have since been labelled a landmark event.
Though this study gives CRISPR treatments foundational proof, the data is still limited to a trial of six subjects. The nascency of the technology, naturally, raises more questions than it answers. These questions are varied and cover everything from long-term impact to CRISPR’s effectiveness over time. There is also no data on the long-term consequences of CRISPR in terms of safety. Neither is there data to indicate its effectiveness in any condition except a very rare, inherited condition. Yet, CRISPR has been a saviour for those treated in the trial for transthyretin amyloidosis. Previously, the only treatments available to the patients were liver transplants or diflunisal, a generic that steadied the transthyretin protein and reduced the pace of nerve damage.
CRISPR and its role in disease
One of the causes of cancer is poor genetic code or DNA. Testing such sequences in the lab with CRISPR lets scientists find patterns in the biological roots of cancer and understand how cancer might develop. Currently, this is being done for glioblastoma, a sort of brain tumour. Altering the cancerous cells in a condition like glioblastoma could allow choosing components fundamental to the cells’ life. This makes such cells more suited for treatment in the future. Additionally, CRISPR can be used to find how cancer cells develop resistance to drugs.
Cancer is a collective of over 200 diseases and chances of it being treatable by a single cure are slim. This applies to CRISPR as well. There is currently no evidence that CRISPR can treat a form of cancer. However, the possibilities for research in this direction can be explored. Among these, an area of interest is cell therapy, which alters certain immune granting cells in people to achieve an effect. A recent landmark study on six people suffering from a fatal and rare state called transthyretin amyloidosis suggests that CRISPR-Cas9 can be carried out to improve the condition. Two participants received a high dose and saw their symptoms (excess misfolded protein) reduced by an average of 87%.
Where is CRISPR research today?
CRISPR holds immense potential, as the tool equips scientists to edit DNA in an unprecedented. CRISPR is currently the most inexpensive and quick way to precisely edit genes. Though CRISPR research is still at a very nascent stage, it promises an expansive impact across different fields. However, there is a sizable gap between the realistic considerations for it to be researched rigorously and the cloud castles built about its rather distant possibilities in the media. Any CRISPR-Cas9 activity or experimentation performed outside of a controlled lab can carry disastrous consequences and risks.
While CRISPR is regarded for its precision, there are concerns about the results when it misses a gene target—a course that is possible. By its nature, DNA is complex and intricate; thus, impacting one gene by cutting it can also hinder the smooth working of other genes and molecules. DNA sequencing is recorded in four chemical letters, increasing the risk of gene strains with similar patterns to be CRISPR mistargets and also raising the chances of damage. That such accidental DNA damage may not be visible in a timely manner is another concern. Its novelty prevents us from knowing how CRISPR would respond to a breadth of situations and conditions, something that isn’t possible to verify without adequate research and testing.
Further, as with any nascent area of research, there are ethical concerns. However, with public dialogue between researchers and experts showing some progress, a recent report by two American bodies, the National Academy of Sciences (NAS) and National Academy of Medicine has encouraged more research before clinical trials on preventing disease can begin.
Conclusion
CRISPR, formally known as CRISPR-Cas9, is a tool that alters, cuts or edits the contents of our DNA. It is divided into two parts: RNA and Cas9. RNA acts as a navigational tool to Cas9, also called ‘molecular scissors’. Recently, in a landmark medical trial, CRISPR reduced symptoms of a genetic condition by 87% in six participants who had minor side effects. Despite its potential applications being promising, research is at a stage where it raises more questions than it gives answers. However, this has not prevented the media and the cultural conversation from building immense hype around its future applications, which remain a distant reality that can be verified through scientific research and testing.
References
- Landmark CRISPR trial shows promise against deadly disease (nature.com)
- What Is CRISPR? (cbinsights.com)
- What is CRISPR-Cas9? | Facts | yourgenome.org
- The gene editor CRISPR won’t fully fix sick people anytime soon. Here’s why | Science | AAAS
- 9 questions about CRISPR genome editing answered – Cancer Research UK – Cancer news
