Adeno-Associated Virus Gene Delivery to Hard-to-Transduce Tissues: Biological Barriers, Engineering Strategies, and Clinical Challenges - PubMed
3 hours ago
- #AAV vectors
- #gene therapy
- #drug delivery barriers
- AAV is a leading gene therapy vector, with clinical successes like Luxturna and Zolgensma.
- Efficient gene delivery to hard-to-transduce tissues (e.g., retina, deep skeletal muscle, CNS) faces barriers such as structural limitations, preexisting immunity, and dose-dependent toxicities.
- Capsid engineering (rational design, directed evolution, computational methods) aims to enhance tropism and evade immune detection.
- Innovative delivery routes (local, systemic, physical/chemical methods) improve vector bioavailability.
- Modulating intracellular trafficking boosts nuclear delivery of vectors.
- Immunomodulatory strategies help mitigate innate and adaptive immune responses.
- Translational progress is seen in neuromuscular and retinal diseases, though challenges persist.
- Future advancements may involve next-generation capsids, smart vector systems, and integrated delivery platforms to broaden AAV applications.