Genetic Therapies for
Sickle Cell Disease
Genetic therapies are experimental techniques for treating disease that involve changing the patient’s genetic material in some of their cells. One of the methods being tested for sickle cell disease is to introduce a healthy copy of the hemoglobin (the protein molecule that carries oxygen in the blood) gene into the patient’s hematopoietic stem cells, which are the immature cells that can develop into any type of blood cell, including white blood cells, red blood cells, and platelets. After being transplanted into the patient, these cells, which now carry the genes for both sickle globin and healthy globin, produce a continuous supply of red blood cells that make healthy hemoglobin. In the future, these techniques may allow doctors to treat a disorder by inserting a gene into a patient’s cells instead of using medicines or surgery.
Researchers are testing other ways in addition to replacing the abnormal gene in the hematopoietic stem cells with a standard, healthy copy. These include inactivating, or “knocking out,” an abnormal gene that is not functioning properly, as well as introducing a new gene into the body to help fight a disease.
Importantly, while these approaches have the promise to improve quality of life (QOL) the individual will still have cells in the body that contain the sickle gene (the reproductive cells – sperm/egg) and can pass on the gene to future generations.
Although genetic therapy is a promising new treatment option for many rare diseases, the technique is still being studied to make sure that it will be safe and effective. Genetic therapies are currently being tested for diseases that have no other safe and effective cures.
Genome editing (also called gene editing) is a group of technologies that gives scientists the ability to change the DNA in a cell. These technologies allow genetic material to be added, removed, or altered at particular locations in the genome.
Genome editing is of great interest in the prevention and treatment of human diseases and is being explored in a wide variety of diseases, including cystic fibrosis, hemophilia, and sickle cell disease.
CRISPR-Cas9: An example of genome editing
Several approaches to genome editing have been developed: a recent one is known as CRISPR-Cas9, which is short for Clustered Regularly Interspaced Short Palindromic Repeats and CRISPR-associated protein 9. The CRISPR-Cas9 system is faster, cheaper, more accurate, and more efficient than other existing genome editing methods.
How it Works
CRISPR-Cas9 was adapted from a naturally occurring genome editing system in bacteria. The bacteria capture snippets of DNA from invading viruses and use them to create DNA segments known as CRISPR arrays. The CRISPR arrays allow the bacteria to "remember" the viruses (or closely related ones). If the viruses attack again, the bacteria produce RNA segments from the CRISPR arrays to target the viruses' DNA. The bacteria then use Cas9 (or a similar enzyme) to cut the DNA apart, which disables the virus.
Effects of Gene Editing
Changing the DNA in a person is not currently possible, but it is possible to change the DNA in several types of cells, like in some of the stem cells of the bone marrow. The stem cells give rise to mature blood cells, and this can be enough to prevent sickle cell disease. Importantly, this does not change the DNA in the other cells of the body. Therefore, the person who has this type of gene editing treatment can still pass the disease on to their children.
National Library of Medicine
How viruses help find genetic cures
Some genetic therapies are performed by collecting bone marrow cells from a patient, correcting the incorrect DNA in the collected cells, and then returning the modified cells to the body.
Researchers have found ways to use non-infectious parts of certain viruses to make the genetic therapies that correct the incorrect DNA. Viruses are used because of their ability to easily transfer DNA into cells.
This technique has been used in research for many years to treat various diseases, including Severe Combined Immunodeficiency syndrome (SCID), thalassemia, Wiskott-Aldrich syndrome, as well as various cancers.
Viruses and Sickle Cell Disease
One approach being studied for sickle cell disease is using modified viruses to carry or deliver the healthy hemoglobin gene into the body. This is done by removing the parts of the virus that cause disease and by replacing it with the corrected genetic material (healthy hemoglobin), which is then returned to the patient.
A group of viruses, called lentiviruses, is used and when used in genetic therapy, they are called lentiviral vectors. HIV, one example of Lentiviral vectors, do not contain the infectious part of the virus and cannot give a person HIV/AIDS.