ArticleThe journal of gene medicine2018
Neuraminidase-mediated desialylation augments AAV9-mediated gene expression in skeletal muscle.
Article in The journal of gene medicine, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.
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Who cites it
8 citing papers in PubMed, 11 citations in OpenAlex.
- Integrated AAV optimization enables efficient gene delivery to kidney in murine and human tissue.Research square · 2025Article
- Sildenafil increases AAV9 transduction after a systemic administration and enhances AAV9-dystrophin therapeutic effect in mdx mice.Gene therapy · 2024Article
- Fast, multiplexable and efficient somatic gene deletions in adult mouse skeletal muscle fibers using AAV-CRISPR/Cas9.Nature communications · 2023Article
- TRIM72 Alleviates Muscle Inflammation in mdx Mice via Promoting Mitophagy-Mediated NLRP3 Inflammasome Inactivation.Oxidative medicine and cellular longevity · 2023Article
- Robust AAV Genotyping Based on Genetic Distances in Rep Gene That Are Maintained by Ubiquitous Recombination.Viruses · 2022Article
- Article
- Next Step in Gene Delivery: Modern Approaches and Further Perspectives of AAV Tropism Modification.Pharmaceutics · 2021Review
- Noninvasive In Vivo Quantification of Adeno-Associated Virus Serotype 9-Mediated Expression of the Sodium/Iodide Symporter Under Hindlimb Ischemia and Neuraminidase Desialylation in Skeletal Muscle Using Single-Photon Emission Computed Tomography/Computed Tomography.Circulation. Cardiovascular imaging · 2019Article
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
backgroundFollowing systemic delivery, AAV9-mediated gene expression is significantly increased in ischemic versus non-ischemic muscle, suggesting that AAV9 is an attractive vector for treating peripheral arterial disease. Potential mechanisms underlying ischemia-augmented expression include: (i) increased vascular permeability and (ii) "unmasking" of endogenous AAV9 receptors. In the present study, we aimed to reconstitute the ischemic induction of AAV9 in vivo, using local injection of histamine (to increase vascular permeability) and neuraminidase (to desialylate cell surface glycans).
methodsBioassays were performed to optimize the effects of histamine and neuraminidase after intramuscular injection. Histamine and/or neuraminidase were then injected intramuscularly shortly before intravenous injection of an AAV9 vector expressing luciferase. Luciferase expression was serially assessed with bioluminescence imaging. At the end of the study, tissues were harvested for assays of luciferase activity and AAV9 genome copy number aiming to assess AAV-mediated gene expression and transduction, respectively.
resultsIntramuscular injection of either neuraminidase or neuraminidase plus histamine significantly increased both transduction and gene expression, whereas histamine alone had little effect. Pre-injection with neuraminidase increased AAV9-mediated gene delivery by four- to nine-fold and luciferase activity by 60-100-fold. Luciferase activity in neuraminidase-injected muscle was > 100-fold higher than in any off-target tissue (including heart, liver and brain).
conclusionsThe ischemic induction of AAV9-mediated gene expression in muscle can largely be reconstituted by pre-injecting neuraminidase intranmuscularly. This strategy may prove useful in future human gene therapy protocols as a quick and efficient means to selectively target systemically injected AAV9 to localized regions of muscle, thus decreasing the potential for adverse effects in off-target tissues.
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