Contaminating plasmid sequences and disrupted vector genomes in the liver following adeno-associated virus gene therapy
Great Ormond Street Hospital · University College London · +13 more institutions
Abstract
Adeno-associated viruses (AAVs) are common vectors in gene therapy but can frequently cause liver complications in patients. The mechanisms underlying AAV-related liver toxicity remain poorly understood, posing challenges for effective prevention and intervention. Here we conducted a case study of a child with spinal muscular atrophy type 1 experiencing substantial hepatitis after receiving onasemnogene abeparvovec, undertaking long- and short-read metagenomic sequencing of liver tissue. We identified manufacturing plasmid sequences with complex structures and recombination. Vector genomes had extensive disruption and concatemerization as well as numerous vector-human fusion junctions. We also identified human…
Citation impact
- FWCI
- 78.07
- Percentile
- 100%
- References
- 57
Authors
30- SBSarah Buddle
Great Ormond Street Hospital, University College London
- LKLi-An K. Brown
Great Ormond Street Hospital, University College London
- SMSofia Morfopoulou
Great Ormond Street Hospital, University College London
- OEOscar Enrique Torres Montaguth
Great Ormond Street Hospital, University College London
- MSMariacristina Scoto
Great Ormond Street Hospital, National Institute for Health and Care Research, University College London
Topics & keywords
- Plasmid
- Vector (molecular biology)
- Genome
- Gene
- Genetic enhancement
- Vectors in gene therapy
- Virus
- DNA
- Good health and well-being