ArticleHuman gene therapy2019
New MiniPromoter Ple345 (NEFL) Drives Strong and Specific Expression in Retinal Ganglion Cells of Mouse and Primate Retina.
Article in Human gene therapy, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers, 1 of them a synthesis that pooled it.
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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.
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Who cites it
22 citing papers in PubMed, 1 synthesis or guideline pooled it, 38 citations in OpenAlex.
- Recombinant Adeno-Associated Viral Vectors (rAAV)-Vector Elements in Ocular Gene Therapy Clinical Trials and Transgene Expression and Bioactivity Assays.International journal of molecular sciences · 2020Pooled it
- Integrated intraocular-plasma proteomics reveals conserved biomarkers for diabetic retinopathy progression: a multi-fluid biopsy study.Diabetologia · 2026Article
- Overexpression or Activation of Potassium Channel TASK-3 Protects Retinal Ganglion Cells and Restores Visual Function in Optic Nerve Crush.Investigative ophthalmology & visual science · 2026Article
- MiniPromoters Ple384 (TH) and Ple388 (PITX3) for targeting midbrain dopaminergic neurons in mice and monkeys.Scientific reports · 2026Article
- Exploring the role of VAV2 rare variants in primary open-angle glaucoma: genetic insights and pathophysiological mechanisms.Science China. Life sciences · 2026Article
- AAV vector development, back to the future.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Review
- Review
- New MiniPromoter Ple389 (ADORA2A) drives selective expression in medium spiny neurons in mice and non-human primates.Scientific reports · 2024Article
- rAAV-PHP.B escapes the mouse eye and causes lethality whereas rAAV9 can transduce aniridic corneal limbal stem cells without lethality.Gene therapy · 2023Article
- OnTarget: in silico design of MiniPromoters for targeted delivery of expression.Nucleic acids research · 2023Article
- Development of a translatable gene augmentation therapy for CNGB1-retinitis pigmentosa.Molecular therapy : the journal of the American Society of Gene Therapy · 2023Article
- Improving adeno-associated viral (AAV) vector-mediated transgene expression in retinal ganglion cells: comparison of five promoters.Gene therapy · 2023Article
- Refining the genomic determinants underlying escape from X-chromosome inactivation.NAR genomics and bioinformatics · 2023Article
- Long Non-Coding RNAs in Retinal Ganglion Cell Apoptosis.Cellular and molecular neurobiology · 2023Review
- Intravitreal Injection of AAV for the Transduction of Mouse Retinal Ganglion Cells.Methods in molecular biology (Clifton, N.J.) · 2023Article
- AAV2-Mediated Expression of HspB1 in RGCs Prevents Somal Damage and Axonal Transport Deficits in a Mouse Model of Ocular Hypertension.Translational vision science & technology · 2022Article
- Targeted Expression of Retinoschisin by Retinal Bipolar Cells in XLRS Promotes Resolution of Retinoschisis Cysts Sans RS1 From Photoreceptors.Investigative ophthalmology & visual science · 2022Article
- Tandem pore domain acid-sensitive K channel 3 (TASK-3) regulates visual sensitivity in healthy and aging retina.Science advances · 2022Article
- Transgene distribution and immune response after ultrasound delivery of rAAV9 and PHP.B to the brain in a mouse model of amyloidosis.Molecular therapy. Methods & clinical development · 2021Article
- Human MiniPromoters for ocular-rAAV expression in ON bipolar, cone, corneal, endothelial, Müller glial, and PAX6 cells.Gene therapy · 2021Article
Corrections and comments
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Authors and funding
16 authors at 3 institutions in 2 countries.
Funding
Abstract
Retinal gene therapy is leading the neurological gene therapy field, with 32 ongoing clinical trials of recombinant adeno-associated virus (rAAV)-based therapies. Importantly, over 50% of those trials are using restricted promoters from human genes. Promoters that restrict expression have demonstrated increased efficacy and can limit the therapeutic to the target cells thereby reducing unwanted off-target effects. Retinal ganglion cells are a critical target in ocular gene therapy; they are involved in common diseases such as glaucoma, rare diseases such as Leber's hereditary optic neuropathy, and in revolutionary optogenetic treatments. Here, we used computational biology and mined the human genome for the best genes from which to develop a novel minimal promoter element(s) designed for expression in restricted cell types (MiniPromoter) to improve the safety and efficacy of retinal ganglion cell gene therapy. Gene selection included the use of the first available droplet-based single-cell RNA sequencing (Drop-seq) dataset, and promoter design was bioinformatically driven and informed by a wide range of genomics datasets. We tested seven promoter designs from four genes in rAAV for specificity and quantified expression strength in retinal ganglion cells in mouse, and then the single best in nonhuman primate retina. Thus, we developed a new human-DNA MiniPromoter, Ple345 (NEFL), which in combination with intravitreal delivery in rAAV9 showed specific and robust expression in the retinal ganglion cells of the nonhuman-primate rhesus macaque retina. In mouse, we also developed MiniPromoters expressing in retinal ganglion cells, the hippocampus of the brain, a pan neuronal pattern in the brain, and peripheral nerves. As single-cell transcriptomics such as Drop-seq become available for other cell types, many new opportunities for additional novel restricted MiniPromoters will present.
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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.