ArticleMolecular therapy : the journal of the American Society of Gene Therapy2015
Riboswitch-mediated Attenuation of Transgene Cytotoxicity Increases Adeno-associated Virus Vector Yields in HEK-293 Cells.
Article in Molecular therapy : the journal of the American Society of Gene Therapy, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
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Who cites it
28 citing papers in PubMed, 53 citations in OpenAlex.
- AAV vector production in suspension cells using PEI transfection and sodium butyrate with orthogonal assessment of function and quality.Molecular therapy. Advances · 2026Article
- Mammalian therapeutic riboswitches: Engineering and custom ligands.Molecular therapy. Nucleic acids · 2026Review
- Harnessing natural RNA triplex elements found in lncRNAs MALAT1 and NEAT1 for engineering of novel riboswitch platforms.Nucleic acids research · 2026Article
- Engineering of Small Ribozymes Acting on RNA: What is Needed to Make a New Function Work with an Existing Catalyst?Chembiochem : a European journal of chemical biology · 2025Review
- 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
- Suppression of toxic transgene expression by optimized artificial miRNAs increases AAV vector yields in HEK-293 cells.Molecular therapy. Methods & clinical development · 2024Article
- Producing high-quantity and high-quality recombinant adeno-associated virus by low-cis triple transfection.Molecular therapy. Methods & clinical development · 2024Article
- RNA-based controllers for engineering gene and cell therapies.Current opinion in biotechnology · 2024Review
- A comparative survey of the influence of small self-cleaving ribozymes on gene expression in human cell culture.RNA biology · 2024Article
- Insights from the Construction of Adenovirus-Based Vaccine Candidates against SARS-CoV-2: Expecting the Unexpected.Viruses · 2023Article
- Small-Molecule Aptamer for Regulating RNA Functions in Mammalian Cells and Animals.Journal of the American Chemical Society · 2023Article
- AAV- based vector improvements unrelated to capsid protein modification.Frontiers in medicine · 2023Review
- Time and phenotype-dependent transcriptome analysis in AAV-TGFβ1 and Bleomycin-induced lung fibrosis models.Scientific reports · 2022Article
- Engineering synthetic RNA devices for cell control.Nature reviews. Genetics · 2022Review
- Riboswitches for Controlled Expression of Therapeutic Transgenes Delivered by Adeno-Associated Viral Vectors.Pharmaceuticals (Basel, Switzerland) · 2021Review
- The role of small molecules in cell and gene therapy.RSC medicinal chemistry · 2021Review
- Classification of seed members of five riboswitch families as short sequences based on the features extracted by Block Location-Based Feature Extraction (BLBFE) method.BioImpacts : BI · 2021Article
- Rescue of Adeno-Associated Virus Production by shRNA Cotransfection.Human gene therapy · 2020Article
- Creation of a High-Yield AAV Vector Production Platform in Suspension Cells Using a Design-of-Experiment Approach.Molecular therapy. Methods & clinical development · 2020Article
- High-throughput identification of synthetic riboswitches by barcode-free amplicon-sequencing in human cells.Nature communications · 2020Article
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Cytotoxicity of transgenes carried by adeno-associated virus (AAV) vectors might be desired, for instance, in oncolytic virotherapy or occur unexpectedly in exploratory research when studying sparsely characterized genes. To date, most AAV-based studies use constitutively active promoters (e.g., the CMV promoter) to drive transgene expression, which often hampers efficient AAV production due to cytotoxic, antiproliferative, or unknown transgene effects interfering with producer cell performance. Therefore, we explored artificial riboswitches as novel tools to control transgene expression during AAV production in mammalian cells. Our results demonstrate that the guanine-responsive GuaM8HDV aptazyme efficiently attenuates transgene expression and associated detrimental effects, thereby boosting AAV vector yields up to 23-fold after a single addition of guanine. Importantly, riboswitch-harboring vectors preserved their ability to express functional transgene at high levels in the absence of ligand, as demonstrated in a mouse model of AAV-TGFβ1-induced pulmonary fibrosis. Thus, our study provides the first application-ready biotechnological system-based on aptazymes, which should enable high viral vector yields largely independent of the transgene used. Moreover, the RNA-intrinsic, small-molecule regulatable mode of action of riboswitches provides key advantages over conventional transcription factor-based regulatory systems. Therefore, such riboswitch vectors might be ultimately applied to temporally control therapeutic transgene expression in vivo.
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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.