10 Questions
What is the consequence of overexpressing the transferred gene in thalassemia?
New imbalance of globin chains in red blood cells
What is the ideal target cell for gene therapy?
Stem cells
Why is it essential to culture target cells in vitro?
To facilitate gene transfer
What is the minimum level of expression required to be therapeutic in some enzymopathies?
A few percent of normal expression
What is the ideal precedent for gene therapy?
Show efficacy and safety in a large animal genetic model
Why is it essential to introduce a sufficient number of recipient cells into the patient?
To ensure a significant therapeutic effect
What is the advantage of using stem cells as target cells?
They are self-replicating and eliminate the risk of graft-versus-host disease
What is the purpose of animal studies in gene therapy?
To test the efficacy and safety of the gene therapy
Why are large animal models often preferred over small animal models?
They are more representative of the human disease
What is the significance of the organ in which the gene therapy is targeted?
It determines the number of cells required for a therapeutic effect
Study Notes
What is Gene Therapy
- Gene therapy is the introduction of a biologically active gene into a cell to achieve a therapeutic benefit.
- The first gene therapy product was licensed in the US and Europe in 2012 for the treatment of lipoprotein lipase deficiency.
- Gene therapy has now been approved for the treatment of several more disorders.
Essential Requirements of Gene Therapy for an Inherited Disorder
- Identity of the molecular defect: the affected gene must be known.
- A functional copy of the gene: a complementary DNA (cDNA) clone of the gene or the gene itself must be available.
- An appropriate vector: the ideal vector is safe, readily made, and easily introduced into the target tissue, and it would express the gene of interest for life.
Characteristics of Vectors
- Retrovirus:
- Nontoxic to the cell
- Low number of copies of the viral DNA integrate into the host genome
- Stable
- Infects dividing or nondividing cells
- Adeno-Associated Virus (AAV):
- Infects a wide variety of dividing or nondividing cell types
- Accommodates insertion of longer genes
- Adenovirus:
- Accommodates insertion of small genes
- Elicits strong immune response (restricted to specific cell types)
Additional Essential Requirements
- Knowledge of the pathophysiologic mechanism of the disease
- Favorable risk-to-benefit ratio
- Appropriate regulatory components for the transferred gene
- An appropriate target cell: ideally, the target cell must have a long half-life or good replicative potential in vivo
- Strong evidence of efficacy and safety: cultured cell and animal studies must indicate that the vector and gene construct are both effective and safe
Learn about the introduction of biologically active genes into cells for therapeutic benefits and the essential requirements for gene therapy in inherited disorders.
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