ArticleMolecular therapy : the journal of the American Society of Gene Therapy2020
GPR108 Is a Highly Conserved AAV Entry Factor.
Article in Molecular therapy : the journal of the American Society of Gene Therapy, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 90 papers.
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Who cites it
90 citing papers in PubMed.
- Intracellular trafficking and nuclear compartmentalization of AAV gene delivery.Molecular therapy. Advances · 2026Article
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- AAV2 bypasses direct endosomal escape by using AAVR to access the trans-Golgi network en route to the nucleus.Journal of virology · 2026Article
- Delivery Systems for Therapeutic Genome Editing: Challenges, Innovations, and Future Perspectives.MedComm · 2026Review
- Trends in the Engineering of Adeno-Associated Virus (AAV) for Precision Gene Delivery to the Central Nervous System (CNS).International journal of molecular sciences · 2026Review
- AAV transduction of human glioblastoma cell lines induces perturbation in cell proliferation.Molecular therapy. Oncology · 2026Article
- From CRISPR functional genomics to synthetic interventions: engineering antiviral strategies.Journal of virology · 2026Review
- Productivity and genetic stability of a novel baculovirus vector for multigene expression from independent transgene loci.Molecular therapy. Advances · 2026Article
- Identification of CD164 as an essential entry receptor for divergent adeno-associated viruses.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- GPR108 Negatively Regulates TLR7 Signaling in Imiquimod-Induced Psoriasiform Dermatitis.Immunity, inflammation and disease · 2026Article
- Mechanisms of Adeno-Associated Virus Serotype 9 Vector Characterization and Quality Control through Solid-State Nanopores.ACS nano · 2026Article
- The delivery challenge of adeno-associated virus vector-based gene therapies for neurological diseases.Frontiers in neuroscience · 2026Review
- Translational insights from nonclinical studies of AAV gene therapies for hemophilia: mechanisms underpinning variability and durability of gene expression.Therapeutic advances in hematology · 2026Review
- A Longitudinal 3D Live-Cell Imaging Platform to Uncover AAV Vector-Host Dynamics at Single-Cell Resolution.International journal of molecular sciences · 2025Article
- Saffold virus exploits integrin αvβ8 and sulfated glycosaminoglycans as cooperative attachment receptors for infection.Nature communications · 2025Article
- The amazing AAV capsids: Into the structure-verse.Molecular therapy. Methods & clinical development · 2025Review
- TMEM145 is a key stereociliary component in the link structures of outer hair cells and mediates the secretion of stereocilin and tubby.Nature communications · 2025Article
- Functional orthogonality of parvoviral phospholipase AJournal of virology · 2025Article
- Directed evolution of novel AAV variants using the MCMS library for enhanced CNS tropism and reduced liver targeting in mice.Molecular therapy. Methods & clinical development · 2025Article
- Cardiac-Targeted AAV5-S100A1 Gene Therapy Protects Against Adverse Remodeling and Contractile Dysfunction in Postischemic Hearts.Circulation. Heart failure · 2025Article
30 more citing papers are in PubMed but not listed here.
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11 authors.
Funding
Abstract
Adeno-associated virus (AAV) is a highly promising gene transfer vector, yet major cellular requirements for AAV entry are poorly understood. Using a genome-wide CRISPR screen for entry of evolutionarily divergent serotype AAVrh32.33, we identified GPR108, a member of the G protein-coupled receptor superfamily, as an AAV entry factor. Of greater than 20 divergent AAVs across all AAV clades tested in human cell lines, only AAV5 transduction was unaffected in the GPR108 knockout (KO). GPR108 dependency was further shown in murine and primary cells in vitro. These findings are further validated in vivo, as the Gpr108 KO mouse demonstrates 10- to 100-fold reduced expression for AAV8 and rh32.33 but not AAV5. Mechanistically, both GPR108 N- and C-terminal domains are required for transduction, and on the capsid, a VP1 unique domain that is not conserved on AAV5 can be transferred to confer GPR108 independence onto AAV2 chimeras. In vitro binding and fractionation studies indicate reduced nuclear import and cytosolic accumulation in the absence of GPR108. We thus have identified the second of two AAV entry factors that is conserved between mice and humans relevant both in vitro and in vivo, further providing a mechanistic understanding to the tropism of AAV gene therapy vectors.
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