CRISPR gene-editing treatment for sickle cell disease explained

Summary

This video discusses a groundbreaking method in genetic engineering, where stem cells are harvested from a patient’s bone marrow and modified using CRISPR-Cas9 technology. The stem cells are altered to correct blood system defects by disrupting a specific regulatory element in the genome, which prevents the production of adult hemoglobin and promotes the expression of fetal hemoglobin instead. This modification could offer a permanent cure for diseases like sickle cell anemia, providing hope for patients through genomic manipulation that restores proper red blood cell function and prevents sickling.

Takeaways

• 😀 Stem cells are harvested from a patient’s bone marrow and treated with chemicals to enter the bloodstream.
• 😀 Stem cells are captured based on proteins found on the surface of the cells.
• 😀 Stem cells have the potential to become different types of blood cells, like red blood cells, T cells, and B cells.
• 😀 By modifying these stem cells and returning them to the patient, they can potentially restore a defective blood system.
• 😀 The harvested cells are treated with Cas9, a genome-editing tool that cuts the DNA at a specific location.
• 😀 Cas9 is introduced into cells using electroporation, a process involving a brief electric pulse to open small holes in the cells.
• 😀 The RNA guides the Cas9 protein to a specific site in the genome where it makes a cut in the DNA.
• 😀 The cell's DNA repair mechanisms attempt to fix the cut, often creating mistakes that can disrupt regulatory elements.
• 😀 Disrupting a regulatory element can prevent it from turning off fetal hemoglobin production in red blood cells.
• 😀 Fetal hemoglobin is then produced in red blood cells, preventing them from sickling and potentially curing sickle cell anemia.
• 😀 The process of genome editing offers the possibility of permanent cures for diseases like sickle cell anemia by correcting genetic defects.

Q & A

What is the initial step in the process of stem cell harvesting from patients?

The first step is that patients are placed on a machine that can harvest their bone marrow cells. These cells are liberated using chemicals that allow them to migrate from the bones into the bloodstream.

How are the stem cells captured from the patient's bloodstream?

The stem cells are captured based on specific proteins found on their surface. These proteins enable the cells to be isolated from the bloodstream.

What are stem cells and why are they important in the blood system?

Stem cells are undifferentiated cells that have the ability to give rise to all types of blood cells, including red blood cells, T cells, and B cells. They are important because they can restore any defective component of the blood system.

How are stem cells modified in the described treatment process?

After being harvested, the stem cells are treated with Cas9 nuclease, which is programmed with RNA to target specific locations in the genome. The cells are then shocked with a pulse of electricity to allow the protein to enter the cells and make the necessary genetic modifications.

What role does electroporation play in the genetic modification of stem cells?

Electroporation is used to introduce the Cas9 protein and RNA into the cells by applying a quick pulse of electricity. This opens small holes in the cell membrane, allowing the protein to enter and target the specific location in the genome.

What happens when the Cas9 protein cuts the DNA in the stem cells?

When Cas9 cuts the DNA, it creates a break in the genetic material. The cell's DNA repair machinery attempts to fix the break, but often makes mistakes, which are crucial for the process.

Why is the DNA repair error important in the genetic modification of stem cells?

The error made during DNA repair is important because it disrupts a regulatory element within the genome. This regulatory element typically tells a gene to turn off fetal hemoglobin, but when disrupted, it allows the fetal hemoglobin gene to remain active.

How does the disruption of the regulatory element affect hemoglobin in the modified stem cells?

By disrupting the regulatory element, fetal hemoglobin is no longer turned off and continues to be expressed in the red blood cells. As a result, the red blood cells will contain fetal hemoglobin instead of adult hemoglobin.

What is the effect of fetal hemoglobin on red blood cells?

The presence of fetal hemoglobin prevents red blood cells from changing shape, which means they will no longer sickle, as is the case with adult hemoglobin in diseases like sickle cell anemia.

What is the potential benefit of this genetic modification for patients with blood disorders?

The genetic modification offers the possibility of a permanent cure for patients suffering from diseases like sickle cell anemia by restoring the function of hemoglobin in their blood system.