ArticleMolecular therapy. Methods & clinical development2024
Suppression of toxic transgene expression by optimized artificial miRNAs increases AAV vector yields in HEK-293 cells.
Article in Molecular therapy. Methods & clinical development, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
11 citing papers in PubMed.
- Optimization of PEI-mediated transient transfection for antibody production in Expi293F cells by iron ion supplementation.Biochemistry and biophysics reports · 2026Article
- An engineered helper plasmid generates differential E4orf6 and L4-22/33K gene expression increasing AAV vector production.Gene therapy · 2026Article
- Expanding Transposase Technology to Regulatory Noncoding RNAs for Stable Expression in CHO Cells.Biotechnology journal · 2026Article
- Advancements in delivery systems for in vivo chimeric antigen receptor T-cell therapy in urological diseases.Current urology · 2026Review
- Universal strategy to generate lentiviral vectors encoding lethal proteins.Molecular therapy. Advances · 2026Article
- MicroRNA-based targeting strategies enable AAV-mediated, tissue-selective gene expression in adipose tissue and skeletal muscle of mice.Molecular therapy. Advances · 2026Article
- AAV yield, bioactivity, and particle heterogeneity are impacted by genome size and non-coding DNA elements.Molecular therapy. Methods & clinical development · 2025Article
- Model-guided design of microRNA-based gene circuits supports precise dosage of transgenic cargoes into diverse primary cells.Cell systems · 2025Article
- Evaluation of Purification Methods for Minimizing Transgene Expression Background During Viral Manufacturing.Human gene therapy · 2025Article
- Production of an Oncolytic Adeno-Associated Virus Containing the Pro-Apoptotic TRAIL Gene Can Be Improved by shRNA Interference.International journal of molecular sciences · 2025Article
- Model-guided design of microRNA-based gene circuits supports precise dosage of transgenic cargoes into diverse primary cells.bioRxiv : the preprint server for biology · 2024Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
5 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Adeno-associated virus (AAV) vectors have become the leading platform for gene delivery in both preclinical research and therapeutic applications, making the production of high-titer AAV preparations essential. To date, most AAV-based studies use constitutive promoters (e.g., CMV, CAG), which are also active in human embryonic kidney (HEK)-293 producer cells, thus leading to the expression of the transgene already during production. Depending on the transgene's function, this might negatively impact producer cell performance and result in decreased AAV vector yields. Here, we evaluated a panel of diverse microRNA (miRNA)-based shRNA designs to identify a highly potent artificial miRNA for the transient suppression of transgenes during AAV production. Our results demonstrate that insertion of miRNA target sites into the 3' UTR of the transgene and simultaneous expression of the corresponding miRNA from the 3' UTR of conventional AAV production plasmids (rep/cap, pHelper) enabled efficient silencing of toxic transgene expression, thereby increasing AAV vector yields up to 240-fold. This strategy not only allows to maintain the traditional triple-transfection protocol, but also represents a universally applicable approach to suppress toxic transgenes, thereby boosting vector yields with so far unprecedented efficiency.
Indexed as
Identifiers
What OpenQuestion holds
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.