Antisense Oligonucleotide Therapy
Antisense Oligonucleotide (ASO) Therapy
Key Points
- Synthetic single-stranded nucleic acid sequences that modulate gene expression
- Targets specific messenger RNA (mRNA) sequences
- Revolutionizing treatment of genetic neurological disorders
- Enables precision medicine approach in pediatric genetic conditions
Core Principles
ASO therapy represents a breakthrough in treating genetic disorders by:
- Modifying protein expression at the RNA level
- Providing sequence-specific targeting
- Allowing reversible gene modification
- Enabling treatment of previously untreatable conditions
Molecular Mechanisms
Primary Mechanisms
- RNase H1-mediated degradation
- DNA-RNA hybrid formation
- Enzymatic cleavage of target mRNA
- Reduction in disease-causing protein
- Splicing modulation
- Exon inclusion/exclusion
- Alternative splice site selection
- Cryptic splice site blocking
- Translation arrest
- Steric hindrance of ribosome assembly
- Prevention of protein synthesis
Chemical Modifications
- Phosphorothioate backbone modifications
- 2'-O-methoxyethyl (2'-MOE) modifications
- Locked nucleic acids (LNA)
- Mixed chemistry designs
Clinical Applications
FDA-Approved Indications
- Spinal Muscular Atrophy (SMA)
- Nusinersen (Spinraza®)
- SMN2 splicing modification
- Intrathecal administration
- Duchenne Muscular Dystrophy (DMD)
- Eteplirsen (Exondys 51®)
- Golodirsen (Vyondys 53®)
- Exon skipping therapy
Emerging Applications
- Neurological disorders
- Huntington's disease
- Alzheimer's disease
- ALS
- Genetic disorders
- Cystic fibrosis
- Beta-thalassemia
- Familial hypercholesterolemia
Administration Protocols
Route of Administration
- Intrathecal delivery
- Loading dose schedule
- Maintenance dose intervals
- Aseptic technique requirements
- Intravenous administration
- Dosing calculations
- Infusion protocols
- Monitoring requirements
- Subcutaneous injection
- Site rotation
- Technique optimization
Monitoring Parameters
- Clinical efficacy measures
- Safety monitoring
- Liver function tests
- Renal function
- Platelet counts
- Coagulation parameters
- Disease-specific markers
Clinical Considerations
Patient Selection
- Genetic testing requirements
- Age-specific considerations
- Disease stage evaluation
- Contraindications assessment
Safety Considerations
- Common adverse effects
- Post-lumbar puncture syndrome
- Thrombocytopenia
- Renal toxicity
- Hepatotoxicity
- Risk mitigation strategies
- Prophylactic measures
- Monitoring protocols
- Dose modifications
Treatment Response Assessment
- Clinical outcome measures
- Biomarker monitoring
- Quality of life assessments
- Long-term follow-up protocols
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.
