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• W2897078573 abstract "Targeting specific tissues remains a major challenge to the promise of gene therapy. For example, several strategies have failed to target adeno-associated virus 2 (AAV2) vectors, to bone. We have evaluated in vitro and in vivo the affinity of an AAV2 vector to bone matrix, hydroxyapatite (HA) to treat Mucopolysacccharidosis IVA.To increase vector affinity to HA, an aspartic acid octapeptide (D8) was inserted immediately after the N-terminal region of the VP2 capsid protein. The modified vector had physical titers and transduction efficiencies comparable to the unmodified vector.The bone-targeting vector had significantly higher HA affinity and vector genome copies in bone than the unmodified vector. The modified vector was also released from HA, and its enzyme activity in bone, 3 months post infusion, was 4.7-fold higher than the unmodified vector.Inserting a bone-targeting peptide into the vector capsid increases gene delivery and expression in the bone without decreasing enzyme expression. This approach could be a novel strategy to treat systemic bone diseases." @default.
• W2897078573 created "2018-10-26" @default.
• W2897078573 creator A5008057554 @default.
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• W2897078573 date "2018-10-01" @default.
• W2897078573 modified "2023-10-14" @default.
• W2897078573 title "Tailoring the AAV2 capsid vector for bone-targeting" @default.
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• W2897078573 doi "https://doi.org/10.1038/s41390-018-0095-8" @default.
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