Gene Replacement Therapy in Pediatrics
Gene Replacement Therapy
Gene replacement therapy represents a revolutionary approach to treating genetic disorders by delivering functional copies of defective genes into patients' cells. This therapeutic modality has shown particular promise in pediatric medicine, where early intervention can prevent or minimize disease progression.
Key Concepts
- Therapeutic DNA delivery using viral or non-viral vectors
- Integration into host genome or episomal expression
- Target tissue specificity and expression regulation
- Immune response considerations in pediatric patients
Therapeutic Mechanisms
Vector Systems
- Adeno-Associated Virus (AAV)
- Preferred for pediatric applications due to safety profile
- Limited cargo capacity (~4.7 kb)
- Tissue-specific serotypes available
- Lentiviral Vectors
- Larger cargo capacity (~8 kb)
- Genomic integration capability
- Used primarily in ex vivo applications
Delivery Strategies
- In Vivo Delivery
- Direct administration to target tissue
- Systemic administration with tissue targeting
- Blood-brain barrier considerations
- Ex Vivo Modification
- Cell harvest and modification
- Quality control testing
- Reinfusion protocols
Clinical Applications
FDA-Approved Therapies
- Zolgensma (onasemnogene abeparvovec)
- Treatment for Spinal Muscular Atrophy (SMA)
- Single-dose AAV9 vector therapy
- Optimal results when administered before age 2
- Luxturna (voretigene neparvovec)
- Treatment for RPE65-mediated inherited retinal dystrophy
- Subretinal injection
- Demonstrated vision improvement in pediatric patients
Emerging Applications
- Hemophilia A and B
- Duchenne Muscular Dystrophy
- Severe Combined Immunodeficiency (SCID)
- Beta-thalassemia
- Sickle Cell Disease
Administration Methods
Pre-treatment Evaluation
- Genetic testing confirmation
- Vector immunity screening
- Organ function assessment
- Immunological status evaluation
Administration Protocols
- Systemic Administration
- Weight-based dosing considerations
- Infusion rate protocols
- Pre-medication requirements
- Local Administration
- Surgical planning
- Anesthesia considerations
- Post-procedure monitoring
Patient Monitoring
Short-term Monitoring
- Vital signs and clinical status
- Immune response monitoring
- Vector shedding assessment
- Acute complications management
Long-term Follow-up
- Expression monitoring
- Clinical efficacy assessment
- Growth and development tracking
- Quality of life evaluation
Disclaimer
The notes provided on Pediatime are generated from online resources and AI sources and have been carefully checked for accuracy. However, these notes are not intended to replace standard textbooks. They are designed to serve as a quick review and revision tool for medical students and professionals, and to aid in theory exam preparation. For comprehensive learning, please refer to recommended textbooks and guidelines.
