Hitting your target rather than constantly compromising on the accuracy has a sort of real satisfaction, don’t you agree?
Well, I think this is what the genetic scientists would’ve felt when they finally discovered a precise method of editing genes which is not only target specific but also cost-effective and efficient, making it easier to correct genetic mutations.
Want to guess what that is?
CRISPR.
CRISPR (Clustered Regularly Interspaced Short Palindromic Repeats) is a revolutionary gene-editing technology that allows scientists to precisely edit the DNA sequence of a living organism. Which, by the way, is not only used for issues concerning health but also agriculture and drug development.
I found this really baffling that humans are capable of altering something as small as 10kbp, and I think many people will as well. So, for those who it may interest, I will be exploring the groundbreaking potential of CRISPR and will also be touching on the complex ethical dilemmas of this practice.
What is CRISPR and How Does It Work?
The CRISPR Basics
The first sort of hints about the existence of CRISPR came about in 1987, but it was officially invented in 2009. It is a result of a researcher noticing the unusual repeating DNA sequence during his research. Later it was discovered to be a part of bacterial defense mechanisms against viruses. Leading to the brilliant idea of repurposing the system as gene-editing tool.
How Does It Work?
CRISPR uses a specialised enzyme to cut and alter specific sections of DNA. You can say that it acts as a molecular scissor. It targets a specific DNA sequence with the guide RNA, cuts the DNA using Cas9 enzyme and allows natural DNA repair to alter or replace genetic material.
Is it kind of confusing or ambiguous still? Let me explain:
Okay, So the CRISPR system consists of two molecules that can change the DNA:
1. Cas9
2. A piece of RNA also called guide RNA
The CRISPR Mechanism
CRISPR uses a molecule called guide RNA that matches a specific sequence of the DNA within the cell. Or rather the guide RNA is designed to do so. It acts as a navigating system for the CRISPR leading it to the exact spot of the DNA that requires altering
The role of the Cas9 enzyme in the editing process:
In order to cut the section of DNA that needs to be edited, the CRISPR system uses an enzyme called Cas9 to perform the cutting we’ve been talking about throughout the blog. The Cas9 cuts both strands of the DNA at the precise points.
The repair process:
Now, the cutting causes some damage.
It’s the same as cutting anything at all or specifically cutting the skin. Damage requires repair. And the cells know this, hence the are two main types of repair mechanisms:
- Non-homologous end joining: basically, quickly joining the broken DNA ends together. This method may result in extra insertions or deletion, effectively disrupting a gene which “knocks out” its function.
- Homology-directed repair: occurs in the presence of a DNA template that the cell can use, to repair the break accurately. This allows precise gene editing.
Exactly what we wanted!
Potential Uses of CRISPR Gene Editing
(and I may or may not make a deep and detailed blog post on it)
3 ways CRISPR is being used:
1. Medical Advancements
- Treating Genetic Diseases and could potentially cure genetic disorders like cystic fibrosis, sickle cell anemia, or Huntington’s disease.
- Cancer Treatment: CRISPR plays an important role in developing new ways to target and eliminate cancer cells.
- Organ Transplantation: CRISPR could help modify animal (such as a pig’s) organs for human transplants (xenotransplantation).
2. Agricultural Innovations:
- Crop Improvement: Enhancing crop resistance to diseases, pests, and environmental stressors.
- Livestock Enhancement: Modifying animals for higher yield or disease resistance.
3. Environmental Applications:
- Gene Drives: Introducing CRISPR-modified genes into species populations (e.g., mosquitoes to reduce malaria transmission).
- Conservation Efforts: Reviving extinct species or help protect endangered species, as well as allow them to adapt to environmental changes.
However, like every great scientific or for that matter any discovery and advancement, CRISPR comes with challenges and dilemmas. Whist CRISPR can be and definitely is greatly useful in the health and agricultural aspects, scientists do face ethical dilemmas. Mainly because it alters the genes permanently, undermining human safety and morality.
The Ethical Dilemmas Surrounding CRISPR
So let’s delve into the rocky bit of the topic now…
1. Human Germline Editing:
This basically means to edit embryos and pass genetic changes to future generations. Which is a risk because the changes made may be passed on to the future generations.
Now I don’t know about you but I wouldn’t want to pass on a trait with unforeseeable consequences especially if it is to spread or metaphorically contaminate the gene pool permanently
Concerns: Designer babies, enhancing intelligence or physical traits which creates inequality can become a problem.
I like how every human right now is unique. The variation is almost awe inspiring because nearly all of the 8 billion people are different from the eachother.
But if humans are to design their own children they might as well be clones of one another with minor differences. I say this because with the use of internet and social media I think, babies might become part of the trend culture, with certain features being more popular than the other at different times. They’ll become another one of the thousand things human will be able to customise.
Regulatory Challenges: The moral status of embryo will come in question. Is it acceptable to use embryos for research? Because truthfully hundreds of thousand embryos will be used to research and develop Germline editing. In many schools of thoughts and religions it may be considered unethical to alter and harm a potential human life through embryo use.
2. Risk of Unintended Consequences:
Off-target effects occur when the molecular scissor alters the wrong section of the host genome, causing unintended mutations or changes in the genome. This could arise from CRISPR editing. This will lead to insertions or deletion at unintended locations within the gene. Resulting in chromosomal rearrangement, making therapeutic application harder.
And slightly off topic from unwanted consequences: Cas9 protein itself can sometime trigger an immune response, limiting CRISPR’s therapeutic use.
Some long-term impacts also include potential environmental and health effects that may not be fully understood yet.
Other major problems include:
3. Ownership and Access:
This will cause problems regarding who will control the CRISPR technology and ethical concerns around patenting life forms and genetic sequences. As well as accessibility issues.
This arises questions such as: Will this technology benefit a few, or will it be accessible to all, especially in poorer nations?
However, I will make a blog post going into depth about each of the issues and will make sure to touch on government policies and the role of people in decisions being made surrounding the CRISPR.
Right, enough of the negative but still important aspect of this particular type of gene editing. Let’s look at some success stories because it’s always good to end on a positive note.
CRISPR Success Stories and Ongoing Research
1. Sickle Cell Disease and Beta Thalassemia Treatments
Medical treatments with widely known success include the therapies treating the Sickle cell disease and beta thalassemia treatments. Specifically in 2020, the first patients who got treated using the CRISPR-based gene editing showed sustained relief from the symptoms. The treatment included treating the hematopoietic stem cells to reactivate hemoglobin production to compensate for defective adult hemoglobin.
Click here to read more about it.
To ensure safety and effective long-term effectiveness, clinical trials are being carried with the hope and goal is to get approval for widespread therapeutic use.
2. HIV Therapy
CRISPR has been used to target HIV DNA in a lab setting. Which I think is a massive step towards a potential cure to an infection that killed around 44 million people around the globe since the beginning of the epidemic [source WHO]
3. Blindness
A genetic disorder called Leber Congenital Amaurosis can lead to blindness. Through CRISPR therapy, editing components were directly delivered to retinal cells, aiming to restore some level of vision.
Further trials are being carried out to confirm the efficacy and optimize delivery, with the aim to expanding gene editing options for other types of genetic blindness.
Isn’t it nice to think that humans can potentially eliminate a large proportion of genetic issues, which currently are incurable?
Agriculture
Succes stories aren’t limited to medical and therapeutic circumstances.
CRISPR has been used to increase pest and disease resistance in plants. For example, tomatoes resistant to powdery mildew and rice resistant to bacterial blight have been developed through the use of CRISPR editing.
More research in terms of how to increase nutritional profile and producing plants with drought resistance is being carries out.
Conclusion
So, here are my overall thoughts on the CRISPR gene editing:
This method of gene editing has absolutely revolutionised the approach to genetic diseases and has made gene editing precise, efficient and adaptable. The success stories and further research being carried out is enough to prove the potential it has to cure genetic disorders. Which is great and honestly phenomenal.
Yet despite all this, it still faces ethical issues and has off-target consequences, and fairly so, because it still is relatively new. Hence, the concerns surrounding gene editing in general are valid, because they can bring a “doom” day or era if it manages to affect the gene pool, having unforeseeable impact on the future generations.
Therefore, I’d like to end this blog post with the hope that with responsible research and ethical oversight, CRISPR would one day be able to shape the medicine, agriculture and environmental sectors positively!
-Raniya Abrar