GENE
THERAPY
(STEM
CELLS)
Presented by GROUP 5
Introduction to Gene
Therapy and Stem
Cell Therapy
Gene therapy is an experimental technique that
uses genes to treat or prevent disease. It works
by replacing a faulty gene with a healthy one,
inactivating a mutated gene, or introducing a
new gene to help fight a disease. Gene therapy
holds great promise for treating various
inherited and acquired human diseases.
Stem Cell Gene Therapy Basics
Gene Therapy
Introducing normal, functional genes into cells to replace defective genes and
stop the production of improper proteins.
Stem Cells
Undifferentiated cells that can self-renew and differentiate into specialized cell
types. Stem cells provide a renewable source of cells for gene therapy
The general process of stem cell gene therapy involves:
1. Isolating stem cells from the patient (e.g. from bone marrow, fat tissue, or other sources).
2. Genetically modifying the stem cells in the lab to express a therapeutic gene.
3. Expanding the genetically modified stem cells.
4. Transplanting the engineered stem cells back into the patient.
HISTORY and
PROGRESSION
The concept of using stem cells for gene therapy dates back to the 1960s, but
the field has made significant progress in recent decades:
In 1990, the first successful gene therapy trial treated a 4-
year-old girl with severe combined immunodeficiency (SCID)
due to adenosine deaminase (ADA) deficiency
In the 1990s and early 2000s, several early gene therapy
trials using stem cells reported promising results but also
encountered setbacks, such as the development of
leukemia in some SCID-X1 patients and the death of 18-
year-old Jesse Gelsinger in 1999
HISTORY and
PROGRESSION
Since the early 2010s, gene therapy has experienced a
renaissance with the development of improved viral vectors and
gene editing technologies like CRISPR
In 2016, the first gene therapy product, Strimvelis, was approved
in Europe for ADA-SCID
Several other gene therapies have since been approved,
including treatments for spinal muscular atrophy, hemophilia, and
sickle cell disease
Applications of
Stem Cell Gene Therapy
Stem cell gene therapy is being investigated for the treatment of various genetic disorders,
including:
Monogenic diseases (e.g. cystic fibrosis, Duchenne muscular dystrophy, hemophilia)
Neurodegenerative diseases (e.g. Parkinson's disease, Huntington's disease)
Metabolic disorders (e.g. lysosomal storage diseases)
Cancers (e.g. leukemia, solid tumors)
Cardiovascular diseases
ADVANTAGES
- Stem cells can provide a renewable source of corrected cells
- Gene therapy can potentially treat the underlying cause of genetic
diseases
- Autologous stem cells (from the patient) can reduce the risk of
immune rejection
- Mesenchymal stem cells have immunomodulatory and tissue repair
properties
DISADVANTAGES
- Potential risks include immune reactions, off-target effects, and insertional
mutagenesis
- Gene therapy is complex and expensive to develop
- Long-term safety and efficacy data is still limited for many therapies
Successful Gene Therapies
and Examples
Some notable examples of successful stem cell gene therapies include:
- ADA-SCID: The first successful gene therapy in 1990 treated ADA-SCID by introducing a
healthy ADA gene into the patient's stem cells. The therapy was later approved as Strimvelis.
- X-linked SCID (SCID-X1): Improved gene therapies using modified viral vectors have cured
SCID-X1 in multiple patients, including Agustín, the first patient treated at Boston Children's
Hospital in 2010.
- Sickle cell disease: Gene therapy silences the BCL11A gene in red blood cell precursors,
producing fetal hemoglobin unaffected by the sickle cell mutation.
Advancements in
Science and Technology
Stem cell gene therapy has benefited from major scientific and technological
advancements:
- Improved understanding of the human genome and gene regulation
- Development of better viral vectors and gene editing tools like CRISPR
- Advances in stem cell isolation, culture, and genetic modification techniques
- Improved conditioning regimens to prepare patients for stem cell transplants
Conclusions
The development of effective and safe gene therapy vectors remains a significant challenge in the
field of gene therapy. Researchers are working to address key hurdles, including:
- Improving the efficiency and safety of gene delivery vectors by mitigating immune responses,
developing less immunogenic vectors like AAV, and overcoming tissue-specific barriers
- Controlling transgene expression through appropriate regulation and the development of better
promoters and regulatory elements
- Overcoming scalability and manufacturing challenges, such as scaling up production, ensuring
consistent quality, and reducing high costs
- Designing vectors that can effectively treat the underlying complexity of diverse genetic disorders
and target the right cell types
REFERENCES
[1] [Link]
[2] [Link]
[3] [Link]
[4] [Link]
[5] [Link]
[6] [Link]
[7] [Link]
[8] [Link]
[9] [Link]
[10] [Link]
[11] [Link]
[12] [Link]
[13] [Link]
[14] [Link]
[15] [Link]
Thank
you!