What question did this study set out to answer?

Determine whether adeno-associated virus vectors pseudotyped with capsids from serotypes 2, 3, and 6 can evade neutralizing antibodies and enable repeated gene delivery in the lung.

February 1, 2000Journal of VirologyOpen Access

Repeat Transduction in the Mouse Lung by Using Adeno-Associated Virus Vectors with Different Serotypes

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Authors

CHChristine L. HalbertMuscular Dystrophy Association ERElizabeth A. RutledgeKalispell Regional Medical Center JAJames M. AllenUniversity of the Free State

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Implication

Preclinical study demonstrates successful repeat lung transduction using AAV6 vectors without cross-neutralization from AAV2 in mice, suggesting viable strategies for long-term pulmonary gene therapy.

Key Points

Determine whether adeno-associated virus vectors pseudotyped with capsids from serotypes 2, 3, and 6 can evade neutralizing antibodies and enable repeated gene delivery in the lung.
Administered AAV2 vectors pseudotyped with capsid proteins from serotypes AAV2, AAV3, and AAV6 to mouse lungs to measure primary and repeated transduction efficiencies.
Assessed gene delivery in airway epithelial and alveolar cells after cross-serotype readministration.
Analyzed neutralizing antibody responses and relative vector immunogenicity in sera collected from mice and humans.
AAV6 vectors transduced airway epithelial and alveolar cells at levels equivalent to or higher than AAV2, while AAV3-mediated transduction was substantially lower.
AAV6 transduction was unimpeded by prior exposure to AAV2 or AAV3, and AAV2 transduction was unaffected by prior AAV6 exposure, indicating no cross-reactive neutralizing antibodies.
Initial AAV2 exposure completely blocked transduction upon secondary AAV2 dosing, whereas initial AAV6 administration only partially inhibited repeat AAV6 transduction due to lower serum immunogenicity.

Cite This Study

Halbert et al. (2000) studied this question.

synapsesocial.com/papers/6a197975f2eb401dc78923ac https://doi.org/10.1128/jvi.74.3.1524-1532.2000

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Repeat Transduction in the Mouse Lung by Using Adeno-Associated Virus Vectors with Different Serotypes

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Key Points

Cite This Study

Repeat Transduction in the Mouse Lung by Using Adeno-Associated Virus Vectors with Different Serotypes

Discussion

Member takes

Implication

Key Points

Cite This Study

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