ArticleMolecular therapy : the journal of the American Society of Gene Therapy2011
Preclinical differences of intravascular AAV9 delivery to neurons and glia: a comparative study of adult mice and nonhuman primates.
Article in Molecular therapy : the journal of the American Society of Gene Therapy, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 324 papers.
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Who cites it
324 citing papers in PubMed, 488 citations in OpenAlex.
- Intracellular trafficking and nuclear compartmentalization of AAV gene delivery.Molecular therapy. Advances · 2026Article
- Next generation AAV-F capsid gene therapy rescues disease pathology in a model of pyruvate dehydrogenase complex deficiency.Molecular therapy. Advances · 2026Article
- First pilot study of intrastromal rAAV-PAX6 gene therapy suggests improved corneal thickness and transcription correction in aniridic mouse.Molecular therapy. Advances · 2026Article
- Systemic dual-gene therapy reverses biochemical intoxication in the central metabolic compartment of Bckdha-/- mice.Molecular therapy : the journal of the American Society of Gene Therapy · 2026Article
- QSP model for AAV-mediated antibody delivery in rat brain.Journal of pharmacokinetics and pharmacodynamics · 2026Article
- Noninvasive Focal Gene Delivery into the Cerebellum of Non-Human Primates using Focused Ultrasound.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- AAV transduction of human glioblastoma cell lines induces perturbation in cell proliferation.Molecular therapy. Oncology · 2026Article
- Swine reporter model for preclinical evaluation and characterization of gene delivery vectors.Molecular therapy. Advances · 2026Article
- Tumor-Induced Splenic Remodeling: Mechanisms of Systemic Immunosuppression and Emerging Therapeutic Opportunities.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Review
- Optimization of systemic AAV9 gene therapy in Niemann-Pick disease, type C1 mice.Life science alliance · 2026Article
- Systemic delivery of AAV-GFM1 corrects COXPD1 molecular alterations in Gfm1EMBO molecular medicine · 2026Article
- Article
- AAV-mediated gene therapy in a model of SLC13A5 citrate transporter disorder rescues epileptic and metabolic phenotypes.The Journal of clinical investigation · 2026Article
- Intravenous rAAV9 Produces Time-Resolved Parenchymal Labeling Downstream of the Vasculature in Adult Mice.Biology · 2026Article
- Comparison of AAV9-driven motor neuron transduction following different CNS-directed delivery methods in mice.Scientific reports · 2026Article
- A Head-to-Head Comparison of AAV9 Biodistribution in Mice: Routes of Administration and Age Dependence.Genes · 2026Article
- Targeted gene transfer into developmentally defined cell populations of the primate brain.Cell reports · 2026Article
- Genetic therapies for neurological diseases.Pharmacological reviews · 2026Review
- Molecular mechanisms in podocytopathies: finding suitable targets for a new era of glomerular gene therapy.Clinical kidney journal · 2026Review
- rAAV9 vector biodistribution in nonhuman primate brain and spinal cord following lumbar intrathecal infusion.Frontiers in medicine · 2026Article
264 more citing papers are in PubMed but not listed here.
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
Other labs have previously reported the ability of adeno-associated virus serotype 9 (AAV9) to cross the blood-brain barrier (BBB). In this report, we carefully characterized variables that might affect AAV9's efficiency for central nervous system (CNS) transduction in adult mice, including dose, vehicle composition, mannitol coadministration, and use of single-stranded versus self-complementary AAV. We report that AAV9 is able to transduce approximately twice as many neurons as astrocytes across the entire extent of the adult rodent CNS at doses of 1.25 × 10¹², 1 × 10¹³, and 8 × 10¹³ vg/kg. Vehicle composition or mannitol coadministration had only modest effects on CNS transduction, suggesting AAV9 crosses the BBB by an active transport mechanism. Self-complementary vectors were greater than tenfold more efficient than single-stranded vectors. When this approach was applied to juvenile nonhuman primates (NHPs) at the middle dose (9-9.5 × 10¹² vg/kg) tested in mice, a reduction in peripheral organ and brain transduction was observed compared to mice, along with a clear shift toward mostly glial transduction. Moreover, the presence of low levels of pre-existing neutralizing antibodies (NAbs) mostly occluded CNS and peripheral transduction using this delivery approach. Our results indicate that high peripheral tropism, limited neuronal transduction in NHPs, and pre-existing NAbs represent significant barriers to human translation of intravascular AAV9 delivery.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.