ArticleMolecular therapy. Methods & clinical development2016
Microglia-specific targeting by novel capsid-modified AAV6 vectors.
Article in Molecular therapy. Methods & clinical development, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 87 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
87 citing papers in PubMed, 118 citations in OpenAlex.
- Article
- Targeting Microglial Transcriptional Reprogramming as a Therapy Strategy for Alzheimer's Disease.BioEssays : news and reviews in molecular, cellular and developmental biology · 2026Review
- Retrograde transduction of dopaminergic cells in substantia nigra of the rhesus monkey.Scientific reports · 2026Article
- Macrophage-specific circular RNA circHIPK2, inflammation, and fibrosis after myocardial infarction.European heart journal · 2026Article
- Retrograde transduction of dopaminergic cells in substantia nigra of rhesus monkey.bioRxiv : the preprint server for biology · 2026Article
- The delivery challenge of adeno-associated virus vector-based gene therapies for neurological diseases.Frontiers in neuroscience · 2026Review
- Generation and characterization of a tamoxifen-inducible, Cre driver rat for transgene expression in microglia.Scientific reports · 2025Article
- Generation and characterization of a tamoxifen-inducible, Cre driver rat for transgene expression in microglia.Research square · 2025Article
- Article
- A brief guide for gene delivery to the brain using adeno-associated viral vectors.Molecules and cells · 2025Review
- Alpha-Synuclein and Microglia in Parkinson's Disease: From Pathogenesis to Therapeutic Prospects.Journal of clinical medicine · 2024Review
- Review
- Simple and highly specific targeting of resident microglia with adeno-associated virus.iScience · 2024Article
- A comprehensive review of AAV-mediated strategies targeting microglia for therapeutic intervention of neurodegenerative diseases.Journal of neuroinflammation · 2024Review
- Combination AAV therapy with galectin-1 and SOD1 downregulation demonstrates superior therapeutic effect in a severe ALS mouse model.Molecular therapy. Methods & clinical development · 2024Article
- Use of adeno-associated viruses for transgenic modulation of microglia structure and function: A review of technical considerations and challenges.Brain, behavior, and immunity · 2024Review
- Macrophage activation contributes to diabetic retinopathy.Journal of molecular medicine (Berlin, Germany) · 2024Review
- GLUT1-mediated microglial proinflammatory activation contributes to the development of stress-induced spatial learning and memory dysfunction in mice.Cell & bioscience · 2024Article
- TGF-β1 induces PD-1 expression in macrophages through SMAD3/STAT3 cooperative signaling in chronic inflammation.JCI insight · 2024Article
- Allogenic microglia replacement: A novel therapeutic strategy for neurological disorders.Fundamental research · 2024Review
27 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
12 authors at 1 institution in 1 country.
Funding
Abstract
Recombinant adeno-associated viruses (rAAV) have been widely used in gene therapy applications for central nervous system diseases. Though rAAV can efficiently target neurons and astrocytes in mouse brains, microglia, the immune cells of the brain, are refractile to rAAV. To identify AAV capsids with microglia-specific transduction properties, we initially screened the most commonly used serotypes, AAV1-9 and rh10, on primary mouse microglia cultures. While these capsids were not permissive, we then tested the microglial targeting properties of a newly characterized set of modified rAAV6 capsid variants with high tropism for monocytes. Indeed, these newly characterized rAAV6 capsid variants, specially a triply mutated Y731F/Y705F/T492V form, carrying a self-complementary genome and microglia-specific promoters (F4/80 or CD68) could efficiently and selectively transduce microglia in vitro. Delivery of these constructs in mice brains resulted in microglia-specific expression of green fluorescent protein, albeit at modest levels. We further show that CD68 promoter-driven expression of the inflammatory cytokine, interleukin-6, using this capsid variant leads to increased astrogliosis in the brains of wild-type mice. Our study describes the first instance of AAV-targeted microglial gene expression leading to functional modulation of the innate immune system in mice brains. This provides the rationale for utilizing these unique capsid/promoter combinations for microglia-specific gene targeting for modeling or functional studies.
Identifiers
What OpenQuestion holds
Registered trials
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.