ArticleMolecular therapy. Methods & clinical development2020
AAV-Genome Population Sequencing of Vectors Packaging CRISPR Components Reveals Design-Influenced Heterogeneity.
Article in Molecular therapy. Methods & clinical development, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
41 citing papers in PubMed, 57 citations in OpenAlex.
- Comparative Analysis of rAAV Production from Plasmid-Encoded Versus Chromosomally Integrated rAAV Transgene in HEK293 Cells.International journal of molecular sciences · 2026Article
- Optimizing single molecule, real-time sequencing for enhanced characterization of adeno-associated viral vector genomes.Molecular therapy. Advances · 2026Article
- Pool-packaged AAV libraries exhibit extensive length-dependent and homology-dependent chimerism.Nature biotechnology · 2026Article
- Article
- Dual-targeting snRNA gene therapy rescues STMN2 and UNC13A splicing in TDP-43 proteinopathies.bioRxiv : the preprint server for biology · 2025Article
- ConSeqUMI, an error-free nanopore sequencing pipeline to identify and extract individual nucleic acid molecules from heterogeneous samples.Nucleic acids research · 2025Article
- Quantifying DNA point mutations in commercially available AAV reporter vectors and plasmids.Molecular therapy. Methods & clinical development · 2025Article
- Evaluation of the loading capacity and patterns of packaged DNA in AAV genomes of different sizes using long-read sequencing.Molecular therapy. Methods & clinical development · 2025Article
- AAVone: A cost-effective, single-plasmid solution for efficient AAV production with reduced DNA impurities.Molecular therapy. Nucleic acids · 2025Article
- Recombinant AAV batch profiling by nanopore sequencing elucidates product-related DNA impurities and vector genome length distribution.Molecular therapy. Methods & clinical development · 2025Article
- Implementing a robust platform analytical procedure for measuring adeno-associated virus vector genome titer.Molecular therapy. Methods & clinical development · 2024Article
- Non-encapsidated miRNA contaminants found in AAV preparations.Molecular therapy. Methods & clinical development · 2024Article
- Comprehensive analysis of off-target and on-target effects resulting from liver-directed CRISPR-Cas9-mediated gene targeting with AAV vectors.Molecular therapy. Methods & clinical development · 2024Article
- AAVolve: Concatenated long-read deep sequencing enables whole capsid tracking during shuffled AAV library selection.Molecular therapy. Methods & clinical development · 2024Article
- Multimass Analysis of Adeno-Associated Virus Vectors by Orbitrap-Based Charge Detection Mass Spectrometry.Analytical chemistry · 2024Article
- Adeno-associated virus as a delivery vector for gene therapy of human diseases.Signal transduction and targeted therapy · 2024Review
- Thorough molecular configuration analysis of noncanonical AAV genomes in AAV vector preparations.Molecular therapy. Methods & clinical development · 2024Article
- Modular vector assembly enables rapid assessment of emerging CRISPR technologies.Cell genomics · 2024Article
- Proof-of-concept for multiple AON delivery by a single U7snRNA vector to restore splicing defects in ABCA4.Molecular therapy : the journal of the American Society of Gene Therapy · 2024Article
- Modular vector assembly enables rapid assessment of emerging CRISPR technologies.bioRxiv : the preprint server for biology · 2023Article
Corrections and comments
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Authors and funding
13 authors at 2 institutions in 1 country.
Funding
Abstract
The gene therapy field has been galvanized by two technologies that have revolutionized treating genetic diseases: vectors based on adeno-associated viruses (AAVs), and clustered regularly interspaced short palindromic repeats (CRISPR)-Cas gene-editing tools. When combined into one platform, these safe and broadly tropic biotherapies can be engineered to target any region in the human genome to correct genetic flaws. Unfortunately, few investigations into the design compatibility of CRISPR components in AAV vectors exist. Using AAV-genome population sequencing (AAV-GPseq), we previously found that self-complementary AAV vector designs with strong DNA secondary structures can cause a high degree of truncation events, impacting production and vector efficacy. We hypothesized that the single-guide RNA (sgRNA) scaffold, which contains several loop regions, may also compromise vector integrity. We have therefore advanced the AAV-GPseq method to also interrogate single-strand AAV vectors to investigate whether vector genomes carrying Cas9-sgRNA cassettes can cause truncation events. We found that on their own, sgRNA sequences do not produce a high degree of truncation events. However, we demonstrate that vector genome designs that carry dual sgRNA expression cassettes in tail-to-tail configurations lead to truncations. In addition, we revealed that heterogeneity in inverted terminal repeat sequences in the form of regional deletions inherent to certain AAV vector plasmids can be interrogated.
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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.