ArticleMolecular therapy. Methods & clinical development2021
The impact of lentiviral vector genome size and producer cell genomic to gag-pol mRNA ratios on packaging efficiency and titre.
Article in Molecular therapy. Methods & clinical development, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 53 papers.
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Who cites it
53 citing papers in PubMed.
- Large serine recombinase-mediated gene insertion for high-throughput screens: advantages, design principles, and applications.Nucleic acids research · 2026Review
- Fouling-Free Inertial Microfluidic Cell Clarification for Lentivirus Manufacturing.Biotechnology and bioengineering · 2026Article
- EF-1α-driven nanobody-based CD19-redirected CAR-T cells retain the antitumor efficacy, antigen-driven expansion, and cytokine secretion of CMV-driven counterparts.Molecular and cellular biochemistry · 2026Article
- Lentiviral rescue of UMPS auxotrophy enables drug-free selection and stable vector expression.Molecular therapy. Advances · 2026Article
- A combinatorial domain screening platform reveals epigenetic effector interactions for transcriptional perturbation.Nature communications · 2026Article
- In vivo CAR T cell generation using retargeted and functionalized lentiviral vectors with reduced immunogenicity.Nature communications · 2026Article
- Modulating viscosity improves lentiviral transduction of NK cells: A simple solution to a persistent problem.Molecular therapy. Advances · 2026Article
- T cells assemble lentivirus to solve local delivery of stable gene therapy.Scientific reports · 2026Article
- Engineering single-vector logic-gated CAR T cells with transgene sizes beyond current limitations.Journal for immunotherapy of cancer · 2026Article
- Review
- Installation of dominant-negative mutations inMolecular therapy. Oncology · 2025Article
- Innovative gene engineering strategies to address tumor antigen escape in cell therapy.Journal of translational medicine · 2025Review
- Optimization of velocity receptor transduction in CAR T cells.bioRxiv : the preprint server for biology · 2025Article
- Installation of Dominant-Negative Mutations inbioRxiv : the preprint server for biology · 2025Article
- Lentiviral Vectors: From Wild-Type Viruses to Efficient Multi-Functional Delivery Vectors.International journal of molecular sciences · 2025Review
- Selective Depletion of Cancer Cells with Extrachromosomal DNA via Lentiviral Infection.Cancer research communications · 2025Article
- Genetically encoded and modular subcellular organelle probes reveal dysfunction in lysosomes and mitochondria driven by PRKN knockout.iScience · 2025Article
- Overexpression of BDNF and uPA Combined with the Suppression of Von Hippel-Lindau Tumor Suppressor Enhances the Neuroprotective Activity of the Secretome of Human Mesenchymal Stromal Cells in the Model of Intracerebral Hemorrhage.International journal of molecular sciences · 2025Article
- Pitfalls and strategies of CAR-T therapy in solid tumors and implications for chordoma treatment.Immunotherapy · 2025Review
- Genetically Encoded and Modular SubCellular Organelle Probes (GEM-SCOPe) reveal lysosomal and mitochondrial dysfunction driven bybioRxiv : the preprint server for biology · 2025Article
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2 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Lentiviral vectors are showing success in the clinic, but producing enough vector to meet the growing demand is a major challenge. Furthermore, next-generation gene therapy vectors encode multiple genes resulting in larger genome sizes, which is reported to reduce titers. A packaging limit has not been defined. The aim of this work was to assess the impact of genome size on the production of lentiviral vectors with an emphasis on producer cell mRNA levels, packaging efficiency, and infectivity measures. Consistent with work by others, vector titers reduced as genome size increased. While genomic infectivity accounted for much of this effect, genome sizes exceeding that of clinical HIV-1 isolates result in low titers due to a combination of both low genomic infectivity and decreased packaging efficiency. Manipulating the relative level of genomic RNA to gag-pol mRNA in the producer cells revealed a direct relationship between producer cell mRNA levels and packaging efficiency yet could not rescue packaging of oversized genomes, implying a de facto packaging defect. However, independent of genome size, an equimolar ratio between wild-type gag-pol mRNA and vector genomic RNA in producer cells was optimal for titer.
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