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Tag: sickle cell disease

Clinical Trials to Cure Sickle Cell Disease Using CRISPER Technology

The University of Illinois Chicago participates in clinical trials to cure severe red blood congenital diseases such as sickle cell anemia by safely modifying the DNA of patients’ blood cells. In the CRISPR-Cas9 Gene Editing for Sickle Cell Disease, researchers reported that gene editing modified stem cells’ DNA by deleting the gene BCL11A. This gene is responsible for suppressing fetal hemoglobin production. Then, stem cells start producing fetal hemoglobin so that patients with congenital hemoglobin defects make enough fetal hemoglobin to overcome the effect of the defective hemoglobin that causes their disease.

Sickle cell disease is an inherited defect of the hemoglobin that causes the red blood cells to become crescent-shaped. These cells can lyse and obstruct small blood vessels, depriving the body’s tissues of oxygen.


The first two patients to receive the treatment have had successful results and continue to be monitored. Rondelli is on the steering committee for an international clinical trial. The gene manipulation does not use a viral vector as with other gene therapy studies, but this is done with electroporation which is known to have a low risk of off-target gene activation, according to Rondelli. As the strand for the hemoglobin production is very small, being off-target would not allow the treatment to work.

The treatment is created by a small strand of DNA from stem cells that don’t have the gene BCL11A. Researchers do this by editing the strand of DNA by splitting the DNA with a Helicase protein. Then once it is split, it begins to replicate the DNA using small RNA fragments. The researchers then use a specific strand of RNA that does not have a defect. Since they do not have this particular gene, they can produce hemoglobin freely. Now that the cells are producing hemoglobin, they should be able to create enough to stop the blood cells from crescenting. They insert the DNA by electroporation, where the doctors then introduce electronic waves that allow the cell to open. Once the cell is open, the DNA can enter the blood cells.


This clinical trial is still in its early stages, so it is not used around the world. Though it is promising, it has not been through enough trials. I am not sure if it will get to that stage, do you?


CRISPR to the Rescue

If you are reading this right now, it means you are not blind. Aren’t you so fortunate to have healthy vision? Others aren’t as lucky. The genetic disorder of blindness is something that effects many people.  However, what if I told you that there may be a way to prevent the passing of a genetic mutation such as blindness? It’s called CRISPR.

Before I get into how CRISPR can help prevent blindness, must know what CRISPR is. CRISPR, short for CRISPR-Cas9, is a tool used for editing genes of organisms by modifying the DNA. By changing the DNA sequence, this causes for a change in gene function. Essentially, CRISPR acts as a scissor that is able to cut and edit the DNA sequence.

The way genes are manipulated is by having the components of one CRISPR sent over to another CRISPR, which then alters the structure of the sequence manually, and is called “gene editing”. This phenomenon was discovered only in 2017 when a University in Japan was able to capture and reveal to the world the exact process of this gene editing. Genes are compromised of chemical bases that bind together to form a sequence and every sequence creates something different. For example the sequence GATC when genetically edited with CRISPR can turn into CATG by just switching the C and G. This may seem small but can have a much larger effect on the organism.

This method can directly be used to alter the genetic mutation that causes blindness in a person by finding the spot in the genetic code in that is the root of the mutation and editing it to become normal. Another new way that CRISPR gene editing can be used is to combat sickle cell disease. This disease that causes the creation of mutated hemoglobin resulting in blood clots can also be fixed. Sickle cell disease effects 100,000 people in the US, and can only currently be treated with bone marrow transplants, but this can lead to other health issues according to Dr. Markus Mapara who studies CRISPR. DNA orbit animated

Through CRISPR, as found by Dr. Dounda and Dr. Charpentier, they can direct the Cas9 protein part of CRISPR, through a programable RNA, to locate specific areas of genetic code, in particular ones that are the root of a mutation that causes health issues such as Sickle cell disease. As we mentioned before, the CRISPR can then remove and replace the specific area with one that doesn’t result in the genetic mutation.

While there may be other treatments for these diseases, CRISPR is certainly the safer, healthier, and more effective way to combat them. They also haven’t had too much research on it yet, so we are only getting more and more information as time goes on. I personally don’t have any genetic mutations that I know of, but I know many people who do and who this could help. Hopefully we will be able to master the technique and put an end to genetic mutations!


Modifying Genes to Cure a Blood Disease?

Helen Bolando, a 16 year old living with sickle cell disease, recently became the youngest recipient of an experimental treatment at Boston Children’s Hospital. This treatment made her the youngest person to have her DNA manipulated in hopes of reversing sickle cell’s effects. 

What is sickle cell disease?

Sickle cell disease is a disorder caused by a gene mutation that causes the shape of blood cells to resemble that of a crescent. Characteristics of sickle disease include a low red blood cell count and frequent infections. Due to their shape, blood cells in individuals with sickle cell cells break down too early, causing a lack thereof. This lack of blood cells is known as sickle cell anemia and causes a multitude of symptoms ranging from fatigue and shortness of breath, to delayed growth in children. Painful episodes are also common due to the shape of the red blood cells. Their crescent shape causes blockages in blood vessels, depriving organs and tissues of oxygen, sometimes leading to organ failure. 

A new gene therapy?

Researchers at Boston Children’s Hospital have found that hemoglobin genes (genes found in the blood) are only active in the preceding red blood cells. These genes are only active for 4-5 days before red blood cells mature and when they’re active, they communicate with other cells through communication such as long distance signaling, as we’ve learned earlier in our bio class . The question for researchers is as follows: “How do you manipulate a gene, or put a gene in, so it is expressed only in those cells and at high levels?”  New treatments to solve this burning question include the extraction of immature blood cells from patient’s bone marrow. These stem cells are then genetically modified and re-infused in hopes of creating new, healthy blood cells. Even more interestingly, scientists have found that fetal blood cells have an absence of sickle cells and are testing ways to block the gene that stops fetal hemoglobin production and begins that of adult hemoglobin.Bluebird Bio, a biotech company in Cambridge, Mass conducted a study during which nine patients were treated with gene therapy. Results stated that four patients of the nine who were  treated at least six months earlier, produced enough hemoglobin to no longer have the symptoms of sickle-cell disease!

Researchers are making incredible strides in solving this painful disease using extremely creative and innovative techniques! Are there any other methods of solving sickle cell disease you can think of  based on what we’ve learned so far about cell communication? 



Editing Sickle Cell Disease…

CRISPR gene-editing has recently been involved in the studies of sickle-cell anemia, a gene mutation that causes a decline in children’s health. Sickle cell anemia makes it difficult for oxygen to transport sufficiently throughout the body due to unhealthy blood cells. Some symptoms of the condition are shortness of breath, pale skin, colder body temperatures, headaches, etc…

Photo by SciTechTrend

Looking at sickle-cell anemia from a molecular standpoint, the mutation alters the red-blood cell by producing the wrong form of molecule which is referred to as a subunit. Out of the four subunits in hemoglobin, an “adult-expressed” subunit also known as beta” is produced. In contrast, fetal subunits create “gamma” subunits which are the appropriate molecules in red blood cell development for children. The unfortunate results of a mutated gene are crescent-like and inflexible red blood cells, which can form blockages against the flow of blood and oxygen through blood vessels.

In the past, scientists have been able to increase the gamma production in hemoglobins by “reversing” beta subunits to gamma subunits through a form of therapy, yet in a recent study scientist dove deeper to prevent the mutation as a whole. With gene editing technology, CRISPR has been reported to be useful in putting an end to the hereditary mutation. In that, scientists can identify the mutation and cut the DNA target out by using CRISPR. A specific piece of the DNA, also known as the “control section”, is introduced to gamma subunits during a  process of molecular conversion therapy and the ends of the control section are placed together after the mutated code for the gene is removed. Ultimately, this is said to reduce the adult-expressed subunits and stimulate higher levels of gamma subunits in fetal hemoglobins so that young children affected by sickle cell can avoid invasive treatments in their future.


The Child that Saved Millions

Thousands of years ago a child was born in west Africa with genetic mutation that altered the shape of his/her hemoglobin. This mutation wasn’t harmful because each person has two copies of every gene and the other gene was normal and so they lived and passed on their mutated gene that would save millions of lives.

The gene spread across all of Africa and into parts of southern Europe and India. Every so often two people with the gene would make a child that had two copies of the gene. The child would no longer be able to produce normal hemoglobin. As a result, their red cells became defective and clogged their blood vessels. The condition, now known as sickle cell anemia, leads to extreme pain, difficulty with breathing, kidney failure and even strokes. Most people with this disease die before 40.

In the early 1900s doctors in the U.S first noticed this disease and called its sickle cell anemia because of the way the cells look. Most cases were found in African Americans and studies showed that 8 percent of African Americans had some sickle-shaped blood cells, yet the vast majority had no symptoms at all.

By 1950 doctors had discovered that sickle cell anemia was an incomplete dominance trait and the people who had one copy of the mutated and one of the normal gene showed no symptoms. They soon found out the sickle cell anemia was not unique to the U.S in fact the gene turned up in high rates across Africa, southern Europe and into India. Genetically speaking this made no sense because having two copies of the trait was so deadly it would be most likely that the mutation would have become rarer with each generation.

In 1954 a geneticists Anthony C. Allison observed that people in Uganda who carried a copy of the sickle cell mutation had lower rates of getting malaria. Later research confirmed Dr. Allison’s findings. It seems that the sickle cells defend against malaria by starving the single-celled parasite that causes the disease. The parasite feeds on hemoglobin, and so it’s likely that it can’t grow on the sickle cell version of the molecule.

Babies Save the Day?

No, a bionic baby did not come and save today’s world from global warming but in fact, embryonic cells could potentially save those who suffer from Sickle Cell Disease.

Sickle Cell Disease occurs as a result of a DNA letter change in the gene for hemoglobin, the main protein that carries oxygen for red blood cells. It is possible for the single mutation in the amino acid sequence to affect the entire protein because, as I learned in class, the chain of amino acids, formed by peptide bonds, constitutes the primary structure of proteins.

A recent study conducted by researchers at Johns Hopkins have found that sickle cell disease, a disease that can be very debilitating and affects mostly African Americans, can be cured with the use of stem cells. This is important because the only cure that has been found so far is bone marrow transplants, which can be very painful and is not always successful. The researchers isolated a patient’s own bone marrow cells and used them to generate induced pluripotent stem cells, which are adults cells that can be reprogrammed into embryonic cells. These embryonic cells can then be coaxed into red blood cells, through the use of growth factors.

Despite this progress, Dr. Linzhao Cheng states that, “these immature red blood cells still behave like embryonic cells, and as a result are unable to turn on high enough levels of the adult hemoglobin gene” . The cells still need to be coaxed into mature red blood cells.

Even if these cells can be coaxed into maturity, can they be used to cure Sickle Cell Disease? Can babies actually save the day?

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