ArticleMolecular therapy. Methods & clinical development2019
GluA4-Targeted AAV Vectors Deliver Genes Selectively to Interneurons while Relying on the AAV Receptor for Entry.
Article in Molecular therapy. Methods & clinical development, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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Who cites it
11 citing papers in PubMed, 24 citations in OpenAlex.
- Targeted Intracellular Delivery via Precision Programming of ARRDC1-Mediated Microvesicles.Journal of extracellular vesicles · 2025Article
- Engineered microRNA scaffolds for potent gene silencing in vivo.Scientific reports · 2025Article
- T-cell specific in vivo gene delivery with DART-AAVs targeted to CD8.Molecular therapy : the journal of the American Society of Gene Therapy · 2024Article
- Review
- Hardwiring tissue-specific AAV transduction in mice through engineered receptor expression.Nature methods · 2023Article
- Precision medicine: In vivo CAR therapy as a showcase for receptor-targeted vector platforms.Molecular therapy : the journal of the American Society of Gene Therapy · 2022Review
- Fantastic AAV Gene Therapy Vectors and How to Find Them-Random Diversification, Rational Design and Machine Learning.Pathogens (Basel, Switzerland) · 2022Review
- Lentiviral and adeno-associated vectors efficiently transduce mouse T lymphocytes when targeted to murine CD8.Molecular therapy. Methods & clinical development · 2021Article
- Emerging Concepts in Vector Development for Glial Gene Therapy: Implications for Leukodystrophies.Frontiers in cellular neuroscience · 2021Review
- Recombinant Antibodies in Basic Neuroscience Research.Current protocols in neuroscience · 2020Review
- Review
Corrections and comments
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Authors and funding
12 authors at 8 institutions in 4 countries.
Funding
Abstract
Selective gene delivery into subtypes of interneurons remains an important challenge in vector development. Adeno-associated virus (AAV) vector particles are especially promising for intracerebral injections. For cell entry, AAV2 particles are supposed to attach to heparan-sulfate proteoglycans (HSPGs) followed by endocytosis via the AAV receptor (AAVR). Here, we assessed engineered AAV particles deficient in HSPG attachment but competent in recognizing the glutamate receptor 4 (GluA4, also known as GluRD or GRIA4) through a displayed GluA4-specific DARPin (designed ankyrin repeat protein). When injected into the mouse brain, histological evaluation revealed that in various regions, more than 90% of the transduced cells were interneurons, mainly of the parvalbumin-positive subtype. Although part of the selectivity was mediated by the DARPin, the chosen spleen focus-forming virus (SFFV) promoter had contributed as well. Further analysis revealed that the DARPin mediated selective attachment to GluA4-positive cells, whereas gene delivery required expression of AAVR. Our data suggest that cell selectivity of AAV particles can be modified rationally and efficiently through DARPins, but expression of the AAV entry receptor remains essential.
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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.