ArticleMolecular therapy. Methods & clinical development2015
Multigenic lentiviral vectors for combined and tissue-specific expression of miRNA- and protein-based antiangiogenic factors.
Article in Molecular therapy. Methods & clinical development, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers.
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Who cites it
37 citing papers in PubMed, 51 citations in OpenAlex.
- RNA therapeutics: current status and future directions.Signal transduction and targeted therapy · 2026Review
- Engineering high-titer lentiviral vectors for robust expression of RNA-based gene circuits.bioRxiv : the preprint server for biology · 2026Article
- AAV-mediated multiple gene therapy combining VEGFA-targeting miR-agshRNAs and PEDF for the suppression of choroidal neovascularization.Molecular therapy. Nucleic acids · 2026Article
- Nanobody-based gene therapy targeting complement component C3 reduces choroidal neovascularization in mice.Molecular therapy. Methods & clinical development · 2025Article
- Therapeutic Applications of Poly-miRNAs and miRNA Sponges.International journal of molecular sciences · 2025Review
- Ocular delivery of Pigment Epithelium-Derived Factor (PEDF) as a neuroprotectant for Geographic Atrophy.Aging and disease · 2024Article
- Subretinal AAV delivery of RNAi-therapeutics targetingMolecular therapy. Methods & clinical development · 2024Article
- CRISPR/Cas9 mediated specific ablation of vegfa in retinal pigment epithelium efficiently regresses choroidal neovascularization.Scientific reports · 2023Article
- Lentiviral Vectors for Ocular Gene Therapy.Pharmaceutics · 2022Review
- Article
- Delivery of nVEGFi using AAV8 for the treatment of neovascular age-related macular degeneration.Molecular therapy. Methods & clinical development · 2022Article
- Pigment Epithelium-Derived Factor-Loaded PEGylated Nanoparticles as a New Antiangiogenic Therapy for Neovascularization.Journal of diabetes research · 2022Article
- MicroRNAs in laser-induced choroidal neovascularization in mice and rats: their expression and potential therapeutic targets.Neural regeneration research · 2021Article
- Targeted Knockout of the Vegfa Gene in the Retina by Subretinal Injection of RNP Complexes Containing Cas9 Protein and Modified sgRNAs.Molecular therapy : the journal of the American Society of Gene Therapy · 2021Article
- Gene-Based Therapeutics for Acquired Retinal Disease: Opportunities and Progress.Frontiers in genetics · 2021Review
- Alterations of Growth and Focal Adhesion Molecules in Human Breast Cancer Cells Exposed to the Random Positioning Machine.Frontiers in cell and developmental biology · 2021Article
- Associations between the Complement System and Choroidal Neovascularization in Wet Age-Related Macular Degeneration.International journal of molecular sciences · 2020Review
- Gene Therapy Intervention in Neovascular Eye Disease: A Recent Update.Molecular therapy : the journal of the American Society of Gene Therapy · 2020Review
- Validation of miR-20a as a Tumor Suppressor Gene in Liver Carcinoma Using Hepatocyte-Specific Hyperactive piggyBac Transposons.Molecular therapy. Nucleic acids · 2020Article
- Pigment Epithelium-Derived Factor as a Possible Treatment Agent for Choroidal Neovascularization.Oxidative medicine and cellular longevity · 2020Review
Corrections and comments
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Authors and funding
9 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Lentivirus-based gene delivery vectors carrying multiple gene cassettes are powerful tools in gene transfer studies and gene therapy, allowing coexpression of multiple therapeutic factors and, if desired, fluorescent reporters. Current strategies to express transgenes and microRNA (miRNA) clusters from a single vector have certain limitations that affect transgene expression levels and/or vector titers. In this study, we describe a novel vector design that facilitates combined expression of therapeutic RNA- and protein-based antiangiogenic factors as well as a fluorescent reporter from back-to-back RNApolII-driven expression cassettes. This configuration allows effective production of intron-embedded miRNAs that are released upon transduction of target cells. Exploiting such multigenic lentiviral vectors, we demonstrate robust miRNA-directed downregulation of vascular endothelial growth factor (VEGF) expression, leading to reduced angiogenesis, and parallel impairment of angiogenic pathways by codelivering the gene encoding pigment epithelium-derived factor (PEDF). Notably, subretinal injections of lentiviral vectors reveal efficient retinal pigment epithelium-specific gene expression driven by the VMD2 promoter, verifying that multigenic lentiviral vectors can be produced with high titers sufficient for in vivo applications. Altogether, our results suggest the potential applicability of combined miRNA- and protein-encoding lentiviral vectors in antiangiogenic gene therapy, including new combination therapies for amelioration of age-related macular degeneration.
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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.