ArticleMolecular therapy : the journal of the American Society of Gene Therapy2014
Vector design Tour de Force: integrating combinatorial and rational approaches to derive novel adeno-associated virus variants.
Article in Molecular therapy : the journal of the American Society of Gene Therapy, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 49 papers.
What it found
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Who cites it
49 citing papers in PubMed, 69 citations in OpenAlex.
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- The amazing AAV capsids: Into the structure-verse.Molecular therapy. Methods & clinical development · 2025Review
- Mapping administration route-dependent transduction profiles of commonly used AAV variants in mice by barcode amplicon sequencing.Molecular therapy. Methods & clinical development · 2025Article
- AAV vector development, back to the future.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Review
- AAVolve: Concatenated long-read deep sequencing enables whole capsid tracking during shuffled AAV library selection.Molecular therapy. Methods & clinical development · 2024Article
- Design and Characterization of a Novel Intravitreal Dual-Transgene Genetic Medicine for Neovascular Retinopathies.Investigative ophthalmology & visual science · 2024Article
- Predictive power of deleterious single amino acid changes to infer on AAV2 and AAV2-13 capsids fitness.Molecular therapy. Methods & clinical development · 2024Article
- Engineering viral vectors for acoustically targeted gene delivery.Nature communications · 2024Article
- Computationally guided AAV engineering for enhanced gene delivery.Trends in biochemical sciences · 2024Review
- Review
- Machine-learning-guided Directed Evolution for AAV Capsid Engineering.Current pharmaceutical design · 2024Review
- Intravitreal injection of a rationally designed AAV capsid library in non-human primate identifies variants with enhanced retinal transduction and neutralizing antibody evasion.Molecular therapy : the journal of the American Society of Gene Therapy · 2023Article
- Exploring the Comprehensive Kozak Sequence Landscape for AAV Production in Sf9 System.Viruses · 2023Article
- Chemical modification of AAV9 capsid with N-ethyl maleimide alters vector tissue tropism.Scientific reports · 2023Article
- Characterization of a Bioengineered AAV3B Capsid Variant with Enhanced Hepatocyte Tropism and Immune Evasion.Human gene therapy · 2023Article
- Review
- Fast and high-throughput LC-MS characterization, and peptide mapping of engineered AAV capsids using LC-MS/MS.Molecular therapy. Methods & clinical development · 2022Article
- Ancestral library identifies conserved reprogrammable liver motif on AAV capsid.Cell reports. Medicine · 2022Article
- Immunogenicity assessment of AAV-based gene therapies: An IQ consortium industry white paper.Molecular therapy. Methods & clinical development · 2022Review
- Identification of Novel Retinal Pericyte-Targeting rAAV Vectors Through Directed Evolution.Translational vision science & technology · 2022Article
Corrections and comments
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Authors and funding
8 authors at 1 institution in 1 country.
Funding
Abstract
Methodologies to improve existing adeno-associated virus (AAV) vectors for gene therapy include either rational approaches or directed evolution to derive capsid variants characterized by superior transduction efficiencies in targeted tissues. Here, we integrated both approaches in one unified design strategy of "virtual family shuffling" to derive a combinatorial capsid library whereby only variable regions on the surface of the capsid are modified. Individual sublibraries were first assembled in order to preselect compatible amino acid residues within restricted surface-exposed regions to minimize the generation of dead-end variants. Subsequently, the successful families were interbred to derive a combined library of ~8 × 10(5) complexity. Next-generation sequencing of the packaged viral DNA revealed capsid surface areas susceptible to directed evolution, thus providing guidance for future designs. We demonstrated the utility of the library by deriving an AAV2-based vector characterized by a 20-fold higher transduction efficiency in murine liver, now equivalent to that of AAV8.
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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.