Gene therapy is an evolving field in pediatric medicine, offering the potential for curing or significantly altering the course of genetic disorders.
Definition and Principles of Gene Therapy
Gene therapy involves modifying or manipulating the expression of a gene or altering the biological properties of living cells for therapeutic purposes. It includes:
- Gene addition: Introducing a functional gene to compensate for a defective one.
- Gene editing: Altering a gene sequence (e.g., CRISPR-Cas9).
- Gene silencing: Using RNA interference or similar methods to suppress harmful gene expression.
Applications in Pediatrics
Gene therapy is particularly promising in children due to the early onset of many genetic diseases. Conditions under study or approved for gene therapy include:
- Inherited Genetic Disorders:
- Cystic Fibrosis: Efforts to correct CFTR gene mutations.
- Spinal Muscular Atrophy (SMA): Use of onasemnogene abeparvovec (Zolgensma).
- Severe Combined Immunodeficiency (SCID): Introduction of corrected genes via viral vectors.
- Hematological Disorders:
- Thalassemia and Sickle Cell Disease: Gene editing to reactivate fetal hemoglobin production or correct beta-globin mutations.
- Metabolic Disorders:
- Lysosomal Storage Diseases (e.g., MLD, MPS): Enzyme replacement through gene therapy approaches.
- Oncological Conditions:
- CAR T-cell therapy for pediatric leukemia.
Techniques and Delivery Methods
- Vectors:
- Viral Vectors: Lentiviruses, retroviruses, and adeno-associated viruses (AAV).
- Non-viral Methods: Liposomes or nanoparticle delivery.
- Ex Vivo Therapy: Cells are genetically modified outside the body and reintroduced.
- In Vivo Therapy: Genetic material is directly delivered to the target tissue.
Ethical Considerations
- Safety: Risks of insertional mutagenesis, immune responses, and off-target effects.
- Access and Equity: High costs may limit availability, raising concerns about equity in pediatric care.
- Long-term Effects: Ongoing monitoring is crucial as treated children grow.