ArticleMolecular therapy. Nucleic acids2022
Subgenomic particles in rAAV vectors result from DNA lesion/break and non-homologous end joining of vector genomes.
Article in Molecular therapy. Nucleic acids, 2022. 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, 27 citations in OpenAlex.
- 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
- Enhancement of therapeutic transgene insertion for treatment of murine phenylketonuria.Molecular therapy. Nucleic acids · 2026Article
- Role of viral protein ratio in the structure and separation of empty and full adeno-associated virus capsids: A molecular dynamics study.Molecular therapy. Advances · 2026Article
- Article
- Development of high-throughput analytical methods for characterization and quantitation of rAAV genome integrity.Molecular therapy. Methods & clinical development · 2025Article
- AAV delivery of full-length SYNGAP1 rescues epileptic and behavioral phenotypes in a mouse model of SYNGAP1-related disorders.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Article
- Quantifying DNA point mutations in commercially available AAV reporter vectors and plasmids.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
- A Robust and Automated Platform for Charge Detection Mass Spectrometry of Megadalton Biotherapeutics.Analytical chemistry · 2025Article
- Antivirotics based on defective interfering particles: emerging concepts and challenges.Frontiers in cellular and infection microbiology · 2025Review
- DNA contamination within recombinant adeno-associated virus preparations correlates with decreased CD34Molecular therapy. Methods & clinical development · 2024Article
- A robust and flexible baculovirus-insect cell system for AAV vector production with improved yield, capsid ratios and potency.Molecular therapy. Methods & clinical development · 2024Article
- Analytical characterization of full, intermediate, and empty AAV capsids.Gene therapy · 2024Article
- Thorough molecular configuration analysis of noncanonical AAV genomes in AAV vector preparations.Molecular therapy. Methods & clinical development · 2024Article
- Inhibition of DNA-dependent protein kinase catalytic subunit boosts rAAV transduction of polarized human airway epithelium.Molecular therapy. Methods & clinical development · 2023Article
- Stowaways in the cargo: Contaminating nucleic acids in rAAV preparations for gene therapy.Molecular therapy : the journal of the American Society of Gene Therapy · 2023Review
- Molecular evaluation and vector integration analysis of HCC complicating AAV gene therapy for hemophilia B.Blood advances · 2023Article
- Article
- Comprehensive Comparison of AAV Purification Methods: Iodixanol Gradient Centrifugation vs. Immuno-Affinity Chromatography.Advances in cell and gene therapy · 2023Article
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Authors and funding
13 authors at 6 institutions in 2 countries.
Funding
Abstract
Recombinant adeno-associated virus (rAAV) vectors have been developed for therapeutic treatment of genetic diseases. Current rAAV vectors administered to affected individuals often contain vector DNA-related contaminants. Here we present a thorough molecular analysis of the configuration of non-standard AAV genomes generated during rAAV production using single-molecule sequencing. In addition to the sub-vector genomic-size particles containing incomplete AAV genomes, our results showed that rAAV preparations were contaminated with multiple categories of subgenomic particles with a snapback genome (SBG) configuration or a vector genome with deletions. Through CRISPR and nuclease-based modeling in tissue culture cells, we identified that a potential mechanism leading to formation of non-canonical genome particles occurred through non-homologous end joining of fragmented vector genomes caused by genome lesions or DNA breaks present in the host cells. The results of this study advance our understanding of AAV vectors and provide new clues for improving vector efficiency and safety profiles for use in human gene therapy.
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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.