The past year has been as eventful as it gets. It was a rollercoaster ride with high highs and low lows. We all are aware of the Coronavirus pandemic and the grievances it caused.
On the contrary, several breakthroughs also took place over the last twelve months. Researchers carried on with their work despite half the closure of half the world. And that’s why they reached new heights with groundbreaking discoveries.
The role of genetic engineering in treating sickle cell disease was perhaps the most significant result that we achieved. Furthermore, the disease has been haunting us for years, and we have achieved little success in treating it with medication.
In this account, you will discover the basics of sickle cell anemia and gene therapy. Followed by how the latter helps treat the former. Read on!
Sickle Cell Disease
All humans form fetal hemoglobin in the beginning. Progressively, we transition into producing regular hemoglobin as we grow older. Alternately, in sickle cell disease, a mutation occurs in the gene that prevents the transition from being successful.
A point mutation occurs in the gene that misproduces an amino acid in the beta chain. Consequently, this change makes the hemoglobin irregular that ultimately affects the RBC’s shapes.
The RBCs become sickle-shaped, and their oxygen-carrying capacity reduces dramatically. Its symptoms include fever, drowsiness, paleness of skin, and episodes of pain. Moreover, the disease can lead to further complications like hypertension and stroke.
Gene Therapy – The Basics
Gene therapy is a procedure in which we deliver nucleic acids into the human to treat ailments. Genetic ailments, to be exact. However, it cannot treat all diseases as there are some complications.
Furthermore, there are some genes in the human genome that can mutate. The mutations may occur due to a multitude of reasons. Nonetheless, the modifications disrupt the original function of the gene. Consequently, this makes our body go rogue, and several diseases arise.
Gene therapy cuts the disease at its cause. Therefore, it is one of the most effective treatments we have discovered to date. Moreover, the discoveries reached a record high in 2020 when scientists found that we can use gene therapy to cure sickle cell disease.
Here are the findings that have the potential to change thousands of lives:
CRISPR Gene Therapy Shows Promise Against Blood Diseases
Emmanuelle Charpentier and Jennifer A. Doudna won the Nobel Prize 2020 for identifying the CRISPR/Cas9 molecular scissors.
CRISPR: Cas9 is a complex of an enzyme and an RNA molecule. The Cas-9 is a restriction endonuclease enzyme. In simple words, it acts as molecular scissors. Firstly, the enzymes cut the DNA at specific sites called the palindromic sequences.
Secondly, it produces sticky ends on the DNA. These ends serve as binding sites for a new gene. Lastly, this gene expresses and takes over the work of the faulty gene.
Sounds like a decent plan, right? It’s more complicated than it sounds.
The CRISPR technique uses the two components mentioned above. They seek to boost the expression of fetal hemoglobin(usually produced in the fetus). Progressively, its production comes to a halt soon after birth.
Researchers believe that producing this fetal hemoglobin could compensate for the deformed hemoglobin in people with sickle cell anemia.
It works in the following four simple steps:
- Firstly, the guide RNA finds the target site where the rest of the procedure will occur.
- Secondly, it leads the enzyme to the location where the insertion will happen.
- Thirdly, the enzyme cuts across the double-stranded DNA. At this moment, the cell gets alert that something fishy is going on. Moreover, the cell tries to repair the DNA.
- Lastly, scientists use this DNA-repair mechanism to change one or more genes’ sequences. And in this way, we get a solution to combat the reduced levels of healthy hemoglobin.
But if we know all these facts, why weren’t professionals using them earlier? You see, scientists were unable to prove the practicality of this hypothesis until the last year. Below are some of the groundbreaking pieces of evidence that we uncovered in the previous twelve months.
Revolutionary Findings In Research
The New England Journal of Medicine reported that gene therapy using CRISPR technology could target the root cause of sickle-cell anemia. Renee Garner commented that the new method could transform the lives of patients who have sickle cell disease.
Furthermore, a bone marrow transplant, the usual treatment of sickle cell disease, can be successful. However, it is out of a common man’s reach as it costs a fortune.
Boston Children’s Hospital and researchers collaborated to discover the CRISPR’s potential. They used a fragment of RNA that switches off the expression of the BCL11A gene in red blood cells.
Moreover, this strategy compliments the fetal hemoglobin. The BCL11A gene is responsible for producing hemoglobin(abnormal in the diseased case). Therefore, when we suppress its production, the viability of HbF increases.
The research featured six participants who were under strict supervision. Finally, after six months of constant treatment, all of them benefited.
Due to its rusticity and accuracy, the CRISPR method appears as a resourceful mechanism. Moreover, it supports genetic editing through the inactivation of the faulty genes (knockout gene − KO) and integration of new sequences (knock-in).
A Patient’s Experience
Charles is a 39-year-old who was suffering from sickle cell anemia in the past. As soon as he got the new gene therapy, his symptoms vanished within months. He said, “I feel like I have a new chance at life, a healthy, full life without any complications.”
He suffered from daily fever, dispersed pain, and dizziness. The innovative tech had rid him of the daily excruciating pain and suffering.
However, as good as the tech has become, scientists believe they can still make it better. Here’s how:
Future Prospects – Simulations
There is always room for improvement as brand-new discoveries are happening minute. The process behind gene therapy is reasonably straightforward; we can cure the condition by replacing the bogus gene with a good one.
But this process occurs at the molecular level, and there can be several complications. That’s why a professional needs to have a precise idea of how the treatment would practically interact with the human body.
Hence, the professionals decided to simulate the interplay. They said, ‘Our group already has comprehensive expertise in simulating membrane amalgamation. These were very advanced state-of-the-art simulations.’
Besides, it gave them a fair estimate of how the genetic vectors would perform, but it also gave them the insight to improve the procedure.
The advancements in medicinal technologies have been truly revolutionary. Sickle cell disease is one of the most frequent genetic disorders. Moreover, it didn’t have a permanent cure before 2020.
Hence, the discovery of gene therapy’s role in treating sickle cell anemia is groundbreaking. It has been a brilliant initiative considering that we know little about genetic treatments. This discovery has paved the way for many forthcoming findings.
Although the research is adept, it still needs more intel regarding how to improve the procedures. With the development of novel methods like this one, medicine’s future is as bright as a star.