Gene Therapy Flashcards
What are the essential requirements for gene therapy for inherited disorders?
Identity of the molecular defect
Functional copy of the gene
Appropriate vector
Knowledge of pathophysiologic mechanism
Favorable risk-to-benefit ratio
Appropriate regulatory components for transferred gene
Appropriate target cell
Strong evidence of efficacy and safety
Regulatory approval
What are the three main components of gene therapy strategies?
Gene delivery vehicle (vector)
Gene to be delivered (transgene)
Physiologically relevant target cell
Name an FDA-approved gene therapy product for spinal muscular atrophy.
Zolgensma (Onasemnogene abeparvovec) for spinal muscular atrophy type 1.
What type of vector is used in Luxturna for treating retinal dystrophy?
Adeno-associated virus (AAV) vector.
Which disease uses lentiviral vectors to arrest cerebral demyelination?
X-linked adrenoleukodystrophy (ALD) with ABCD1 gene.
What is the outcome of gene therapy for Hemophilia B using adeno-associated virus?
Stable expression of Factor IX at 1–7% of normal levels, allowing >20 patients to stop prophylactic treatment.
What are the main risks of gene therapy?
Adverse response to vector
Insertional mutagenesis causing malignancy
Inactivation of essential genes
Gene silencing
Immunotoxicity
Risks of horizontal and vertical transmission
List some diseases that have shown improvements with gene therapy.
Retinal degenerations
Sickle cell anemia
Thalassemia
PKU (Phenylketonuria)
Urea cycle disorders
Familial hypercholesterolemia
α1AT deficiency
What is RNA interference (RNAi) used for in gene therapy?
To reduce the abundance of a toxic or dominant negative protein, e.g., transthyretin amyloidosis.
What is the use of CRISPR/Cas9 gene editing in hematopoietic stem cells?
To treat sickle cell disease and β-thalassemia by inactivating the BCL11 gene.
Give an example of dietary restriction for treating a genetic disease.
Phenylalanine restriction for PKU (Phenylketonuria).
What therapy uses statins and PCSK9 inhibitors?
Treatment for familial hypercholesterolemia heterozygotes.
