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Recombinant adeno-associated virus vectors have significant application value in the genetic research of orthopedic-related diseases. The existing conventional AAV vector systems have obvious shortcomings. The immune response interferes with the expression of transgenes, and the inherent delivery limitations of the vectors need to be compensated by increasing the dosage. This may lead to potential safety risks. This study constructs a nanomicelle material that can synergize with AAV vectors. By interfering with the rigidity characteristics of the cell nucleus and the function of the envelope barrier, it enhances the nuclear entry efficiency of AAV through the passive transport pathway mediated by the nuclear pore complex; at the same time, it reduces the accumulation of viral particles in the cytoplasm and inhibits the antigen presentation process of the capsid protein, weakening the cellular immune response of the organism. The study validates the combined system through two classic bone-related pathological models, confirming that this synergistic system can stably retain the biological efficacy of gene intervention and effectively improve the application limitations of traditional AAV vectors in bone-related research. The rigidity of the nuclear membrane and the regulatory concept of the envelope barrier can be extended to the optimization research of other viral gene vectors targeting bone tissue, enriching the intracellular regulatory strategies for bone gene delivery; it can provide a new entry point for the basic mechanism research of bone metabolic diseases and autoimmune osteoarthropathy; it can promote the cross-fusion of nanofunctional materials and bone gene biology, improving the basic theory of mechanical regulation of biological membranes mediating viral delivery; and based on this mechanism, multi-active factor composite micelles can be developed to further enhance the precision and effectiveness of bone tissue-targeted gene modification.
Original source:
1. Journal: Nature Communications
2. Publication date: March 28, 2026
3. DOI: 10.1038/s41467-026-71194-5
4. Authors: Yangsen Ou, Fuhua Wu, Chunting He, Xun Sun, et al. Research team
