Modulating nuclear stiffness and envelope barrier facilitates AAV nuclear entry and reduces immunogenicity - PubMed
5 hours ago
- #Immunogenicity reduction
- #AAV therapy
- #Nuclear entry
- Pluronic F-127 encapsulating rapamycin (PF127-RAPA) co-administered with AAV vectors enhances transduction efficiency and reduces immunogenicity.
- PF127-RAPA modulates nuclear membrane morphology and mechanical properties, facilitating passive transport via nuclear pore complexes and increasing AAV nuclear entry.
- PF127-RAPA reduces cytoplasmic AAV accumulation, minimizing MHC class I presentation of capsid proteins and attenuating cellular immune responses.
- In mouse models of postmenopausal osteoporosis and rheumatoid arthritis, PF127-RAPA enabled AAV6-SEMA3A to achieve a 75% dosage reduction while maintaining efficacy.
- This nanotechnology approach offers a clinically translatable and cost-effective method to improve AAV-based therapies for osteoimmunological disorders.