ArticleBioconjugate chemistry2024
Precise Manipulation of the Site and Stoichiometry of Capsid Modification Enables Optimization of Functional Adeno-Associated Virus Conjugates.
Article in Bioconjugate chemistry, 2024. 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, 15 citations in OpenAlex.
- Site-Specific Protein Bioconjugation Through Cellular Incorporation of Noncanonical Amino Acids.Angewandte Chemie (International ed. in English) · 2026Review
- An Expanded Toolbox for Versatile Chemical Editing of Adeno-Associated Virus.Angewandte Chemie (International ed. in English) · 2026Article
- Genetically Encoded SpyTag Enables Modular AAV Retargeting via SpyCatcher-Fused Ligands for Targeted Gene Delivery.ACS synthetic biology · 2026Article
- Site-Specific Chemical Conjugation of Recombinant Proteins onto the AAV Capsid.Methods in molecular biology (Clifton, N.J.) · 2026Article
- Reprogramming AAV tropism with tumor-associated targeting ligands.Molecular therapy. Oncology · 2025Article
- A facile chemical strategy to synthesize precise AAV-protein conjugates for targeted gene delivery.Molecular therapy. Oncology · 2025Article
- Development of LC-MS methods for AAV capsid protein quantification and host cell protein profiling.Molecular therapy. Methods & clinical development · 2025Article
- Strategies to Expand the Genetic Code of Mammalian Cells.Chemical reviews · 2025Review
- 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
- Chemical approaches to probe and engineer AAV vectors.Nanoscale · 2024Review
- Directed Evolution of a Bacterial Leucyl tRNA in Mammalian Cells for Enhanced Noncanonical Amino Acid Mutagenesis.ACS synthetic biology · 2024Article
Corrections and comments
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Authors and funding
9 authors at 1 institution in 1 country.
Funding
Abstract
The ability to engineer adeno-associated virus (AAV) vectors for targeted transduction of specific cell types is critically important to fully harness their potential for human gene therapy. A promising approach to achieve this objective involves chemically attaching retargeting ligands onto the virus capsid. Site-specific incorporation of a bioorthogonal noncanonical amino acid (ncAA) into the AAV capsid proteins provides a particularly attractive strategy to introduce such modifications with exquisite precision. In this study, we show that using ncAA mutagenesis, it is possible to systematically alter the attachment site of a retargeting ligand (cyclic-RGD) on the AAV capsid to create diverse conjugate architectures and that the site of attachment heavily impacts the retargeting efficiency. We further demonstrate that the performance of these AAV conjugates is highly sensitive to the stoichiometry of capsid labeling (labels per capsid), with an intermediate labeling density providing optimal activity for cRGD-mediated retargeting. Finally, we developed a technology to more precisely control the number of attachment sites per AAV capsid by selectively incorporating an ncAA into the minor capsid proteins with high fidelity and efficiency, such that AAV conjugates with varying stoichiometry can be synthesized. Together, this platform provides unparalleled control over the site and stoichiometry of capsid modification, which will enable the development of next-generation AAV vectors tailored with desirable attributes.
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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.