Tailoring the AAV2 capsid vector for bone-targeting.
Ontology highlight
ABSTRACT: Background
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.Methods
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.Results
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.Conclusion
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.
SUBMITTER: Almeciga-Diaz CJ
PROVIDER: S-EPMC6266866 | biostudies-literature | 2018 Oct
REPOSITORIES: biostudies-literature
Publications
Tailoring the AAV2 capsid vector for bone-targeting.
Alméciga-Díaz Carlos J CJ Montaño Adriana M AM Barrera Luis A LA Tomatsu Shunji S
Pediatric research 20181015 4
<h4>Background</h4>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.<h4>Methods</h4>To increase vector affinity to HA, an aspartic acid octapeptide (D8) was inserted immediately after the N-terminal region of the VP2 c ...[more]
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