CRISPR Technology Treats SCID Disease

A groundbreaking study led by Dr. Ayal Hendel from the Mina and Everard Goodman Faculty of Life Sciences at Bar-Ilan University, in collaboration with researchers from Tel Aviv University and senior doctors from Sheba Hospital, Tel Hashomer, has introduced an innovative strategy for gene therapy in Severe Combined Immunodeficiency (SCID), commonly known as "bubble children's disease." The strategy is based on CRISPR technology, which enables precise editing of genomes which can alter their functioning. 

A groundbreaking study led by Dr. Ayal Hendel from the Mina and Everard Goodman Faculty of Life Sciences at Bar-Ilan University, in collaboration with researchers from Tel Aviv University and senior doctors from Sheba Hospital, Tel Hashomer, has introduced an innovative strategy for gene therapy in Severe Combined Immunodeficiency (SCID), commonly known as "bubble children's disease."

Understanding SCID
Severe Combined Immunodeficiency (SCID) refers to a group of diseases characterized by failure in white blood cells development, particularly T lymphocyte cells. This deficiency severely impairs the immune system's ability to respond to various disease triggers. Some forms of SCID also affect B cells and natural killer (NK) cells. To protect children with SCID from infections, they were often isolated in a sterile environment resembling a bubble, leading to the disease's nickname.

The Monogenic Nature of SCID
SCID diseases are monogenic, meaning they are caused by a defect in a single gene and can be inherited in various ways. Although babies born with SCID may initially appear healthy, their immune systems become vulnerable to bacterial, viral, or fungal infections due to the decline of maternally transferred antibodies and exposure to environmental pathogens. Without medical intervention to restore the immune system, many infants with SCID do not survive beyond the age of two.

Limitations of Standard Treatment
The standard treatment for SCID involves a bone marrow transplant, wherein the patient receives healthy progenitor cells capable of producing white blood cells to restore the immune system. This treatment is highly effective with a success rate of approximately 90% when the patient and donor have complete genetic compatibility. However, when genetic compatibility is not complete, the success rate decreases to 60%-80%. Factors leading to treatment failure range from patient's failure to accept the transplanted cells to the development of severe diseases caused by the transplant cells attacking the patient's own cells.

Advancing Gene Therapy with CRISPR
To overcome the limitations of bone marrow transplants, researchers explored a more advanced treatment option: genetic engineering of the patient's own blood stem cells to correct the genetic code and cure the disease. Unlike a transplant from an external donor, in this approach, the patient becomes their own donor, significantly reducing the risk of rejection and immune system reactions.

The Study's Focus: RAG2 Gene
In this study, researchers focused on one genetic defect caused by a mutation in the RAG2 gene. The objective was to extract stem cells from the patient's body, genetically edit and repair the damaged genes, and then reintroduce them to the patient’s body.

The CRISPR Technology Approach
To achieve the necessary genetic editing in the patient's stem cells, the researchers needed to replace the defective section of DNA with a new, healthy section. The CRISPR technology enabled

researchers to identify and cut the targeted DNA location, and replace it with the same, healthy segment, and make sure it properly fuses within the patient’s DNA.

The results of the experiment demonstrated the successful repair of the RAG2 gene in Hematopoietic Stem and Progenitor Cells (HSPCs)of RAG2 SCID patient. As hypothesized, replacing the defective segment responsible for the lack of T cell development with a new and normal segment enabled the patient's cells to develop T cells in the lab.

This study validates the feasibility of a genetic editing system in SCID disease, paving the way for the development of similar treatments for other hereditary blood disorders. Although the technology is not yet in clinical use, as the repaired cells have not been reintroduced into the human body, researchers are hopeful that in the coming years, CRISPR technology can be effectively and safely utilized to cure SCID and various other diseases.