ArticleScientific reports2019
Diphtheria Toxin A-Resistant Cell Lines Enable Robust Production and Evaluation of DTA-Encoding Lentiviruses.
Article in Scientific reports, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.
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Who cites it
7 citing papers in PubMed, 16 citations in OpenAlex.
- Universal strategy to generate lentiviral vectors encoding lethal proteins.Molecular therapy. Advances · 2026Article
- Hosts and Heterologous Expression Strategies of Recombinant Toxins for Therapeutic Purposes.Toxins · 2023Review
- Virus-Free Method to Control and Enhance Extracellular Vesicle Cargo Loading and Delivery.ACS applied bio materials · 2023Article
- Efficient cell death mediated by bioengineered killer extracellular vesicles.Scientific reports · 2023Article
- Article
- Design, Synthesis and Characterization of HIV-1 CA-Targeting Small Molecules: Conformational Restriction of PF74.Viruses · 2021Article
- Toward Structurally Novel and Metabolically Stable HIV-1 Capsid-Targeting Small Molecules.Viruses · 2020Article
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
Suicide genes have been widely investigated for their utility as therapeutic agents and as tools for in vitro negative selection strategies. Several methods for delivery of suicide genes have been explored. Two important considerations for delivery are the quantity of delivered cargo and the ability to target the cargo to specific cells. Delivery using a lentiviral vector is particularly attractive due to the ability to encode the gene within the viral genome, as well as the ability to limit off-target effects by using cell type-specific glycoproteins. Here, we present the design and validation of a diphtheria toxin A (DTA)-encoding lentiviral vector expressing DTA under the control of a constituitive promoter to allow for expression of DTA in a variety of cell types, with specificity provided via selection of glycoproteins for pseudotyping of the lentiviral particles. DTA exerts its toxic activity through inhibition of eukaryotic translation elongation factor 2 (eEF2) via adenosine diphosphate (ADP)-ribosylation of a modified histidine residue, diphthamide, at His715, which blocks protein translation and leads to cell death. Thus, we also detail development of DTA-resistant cell lines, engineered through CRISPR/Cas9-mediated knockout of the diphthamide 1 (DPH1) gene, which enable both robust virus production by transfection and evaluation of DTA-expressing virus infectivity.
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