ArticleMolecular therapy : the journal of the American Society of Gene Therapy2015
High capsid-genome correlation facilitates creation of AAV libraries for directed evolution.
Article in Molecular therapy : the journal of the American Society of Gene Therapy, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 31 citations in OpenAlex.
- Pool-packaged AAV libraries exhibit extensive length-dependent and homology-dependent chimerism.Nature biotechnology · 2026Article
- 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
- Cell-penetrating peptide-grafted AAV2 capsids for improved retinal delivery via intravitreal injection.Molecular therapy. Methods & clinical development · 2025Article
- Adeno-associated virus-based gene therapy treats inflammatory kidney disease in mice.The Journal of clinical investigation · 2024Article
- Therapeutic Application and Structural Features of Adeno-Associated Virus Vector.Current issues in molecular biology · 2024Review
- Producing high-quantity and high-quality recombinant adeno-associated virus by low-cis triple transfection.Molecular therapy. Methods & clinical development · 2024Article
- Structure-guided AAV capsid evolution strategies for enhanced CNS gene delivery.Nature protocols · 2023Review
- Exploring the Comprehensive Kozak Sequence Landscape for AAV Production in Sf9 System.Viruses · 2023Article
- A novel dual-plasmid platform provides scalable transfection yielding improved productivity and packaging across multiple AAV serotypes and genomes.Molecular therapy. Methods & clinical development · 2023Article
- Functional roles of the membrane-associated AAV protein MAAP.Scientific reports · 2021Article
- Capsid Proteins Are Necessary for Replication of a Parvovirus.Journal of virology · 2021Article
- Synthetic Biology: Emerging Concepts to Design and Advance Adeno-Associated Viral Vectors for Gene Therapy.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2021Review
- Rapid evolution of blood-brain-barrier-penetrating AAV capsids by RNA-driven biopanning.Molecular therapy. Methods & clinical development · 2021Article
- AAV-Containing Exosomes as a Novel Vector for Improved Gene Delivery to Lung Cancer Cells.Frontiers in cell and developmental biology · 2021Article
- Cross-Packaging and Capsid Mosaic Formation in Multiplexed AAV Libraries.Molecular therapy. Methods & clinical development · 2020Article
- Selection of an Efficient AAV Vector for Robust CNS Transgene Expression.Molecular therapy. Methods & clinical development · 2019Article
- Comprehensive AAV capsid fitness landscape reveals a viral gene and enables machine-guided design.Science (New York, N.Y.) · 2019Article
- Using a barcoded AAV capsid library to select for clinically relevant gene therapy vectors.JCI insight · 2019Article
- Optimization of design and production strategies for novel adeno-associated viral display peptide libraries.Gene therapy · 2017Article
- Perspective on Adeno-Associated Virus Capsid Modification for Duchenne Muscular Dystrophy Gene Therapy.Human gene therapy · 2015Review
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
Directed evolution of adeno-associated virus (AAV) through successive rounds of phenotypic selection is a powerful method to isolate variants with improved properties from large libraries of capsid mutants. Importantly, AAV libraries used for directed evolution are based on the "natural" AAV genome organization where the capsid proteins are encoded in cis from replicating genomes. This is necessary to allow the recovery of the capsid DNA after each step of phenotypic selection. For directed evolution to be used successfully, it is essential to minimize the random mixing of capsomers and the encapsidation of nonmatching viral genomes during the production of the viral libraries. Here, we demonstrate that multiple AAV capsid variants expressed from Rep/Cap containing viral genomes result in near-homogeneous capsids that display an unexpectedly high capsid-DNA correlation. Next-generation sequencing of AAV progeny generated by bulk transfection of a semi-random peptide library showed a strong counter-selection of capsid variants encoding premature stop codons, which further supports a strong capsid-genome identity correlation. Overall, our observations demonstrate that production of "natural" AAVs results in low capsid mosaicism and high capsid-genome correlation. These unique properties allow the production of highly diverse AAV libraries in a one-step procedure with a minimal loss in phenotype-genotype correlation.
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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.