Evidence map›Paper›PMID 41017154›Full record

ArticleMolecular therapy : the journal of the American Society of Gene Therapy2026

A novel multiplex RNAi therapy simultaneously targets Hif1a and Hif2a to defy retinal degeneration in two models of AMD.

Lynn J A Ebner, Cornelia Imsand, Duygu Karademir, Florian Peters, Eva Kiessling, Antonia Fottner, Claudia Matter, Diego S Fajardo, Luca Merolla, Gabriele M Wögenstein and 8 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Molecular therapy : the journal of the American Society of Gene Therapy, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

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.

2 · The registry

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.

3 · Its place in the literature

Who cites it

1 citing paper in PubMed.

  1. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

18 authors.

Lynn J A EbnerLaboratory for Retinal Cell Biology, Department of Ophthalmology, University Hospital Zurich, University of Zurich, Wagistrasse 14, Schlieren, 8952 Zurich, Switzerland.
Cornelia ImsandLaboratory for Retinal Cell Biology, Department of Ophthalmology, University Hospital Zurich, University of Zurich, Wagistrasse 14, Schlieren, 8952 Zurich, Switzerland.
Duygu KarademirLaboratory for Retinal Cell Biology, Department of Ophthalmology, University Hospital Zurich, University of Zurich, Wagistrasse 14, Schlieren, 8952 Zurich, Switzerland.
Florian PetersLaboratory for Retinal Cell Biology, Department of Ophthalmology, University Hospital Zurich, University of Zurich, Wagistrasse 14, Schlieren, 8952 Zurich, Switzerland.
Eva KiesslingLaboratory for Retinal Cell Biology, Department of Ophthalmology, University Hospital Zurich, University of Zurich, Wagistrasse 14, Schlieren, 8952 Zurich, Switzerland.
Antonia FottnerLaboratory for Retinal Cell Biology, Department of Ophthalmology, University Hospital Zurich, University of Zurich, Wagistrasse 14, Schlieren, 8952 Zurich, Switzerland.
Claudia MatterLaboratory for Retinal Cell Biology, Department of Ophthalmology, University Hospital Zurich, University of Zurich, Wagistrasse 14, Schlieren, 8952 Zurich, Switzerland.
Diego S FajardoDepartment of Pediatrics, Powell Gene Therapy Center, University of Florida, Gainesville, FL 32601, USA.
Luca MerollaLaboratory for Retinal Cell Biology, Department of Ophthalmology, University Hospital Zurich, University of Zurich, Wagistrasse 14, Schlieren, 8952 Zurich, Switzerland.
Gabriele M WögensteinLaboratory for Retinal Cell Biology, Department of Ophthalmology, University Hospital Zurich, University of Zurich, Wagistrasse 14, Schlieren, 8952 Zurich, Switzerland.
Ioanna TsiotiLaboratory for Retinal Cell Biology, Department of Ophthalmology, University Hospital Zurich, University of Zurich, Wagistrasse 14, Schlieren, 8952 Zurich, Switzerland.
Larissa P GoversLaboratory for Retinal Cell Biology, Department of Ophthalmology, University Hospital Zurich, University of Zurich, Wagistrasse 14, Schlieren, 8952 Zurich, Switzerland.
Frank BlaserDepartment of Ophthalmology, University Hospital Zurich, 8091 Zurich, Switzerland.
Isabelle MeneauDepartment of Ophthalmology, University Hospital Zurich, 8091 Zurich, Switzerland.
Sanford L BoyeDepartment of Pediatrics, Division of Cellular and Molecular Therapy, University of Florida, Gainesville, FL 32610, USA.
Shannon E BoyeDepartment of Pediatrics, Division of Cellular and Molecular Therapy, University of Florida, Gainesville, FL 32610, USA.
Christian GrimmLaboratory for Retinal Cell Biology, Department of Ophthalmology, University Hospital Zurich, University of Zurich, Wagistrasse 14, Schlieren, 8952 Zurich, Switzerland.
Marijana SamardzijaLaboratory for Retinal Cell Biology, Department of Ophthalmology, University Hospital Zurich, University of Zurich, Wagistrasse 14, Schlieren, 8952 Zurich, Switzerland. Electronic address: marijana.samardzija@usz.uzh.ch.

Funding

Engineering AAV for safe and efficient gene delivery to the human retinaR01EY024280 · NEI · UNIVERSITY OF FLORIDA · PI Shannon Elizabeth Boye · 2014 to 2026
$7.5M
NEI NIH HHS R01 EY024280
6 · The paper itself

Abstract

Age-related tissue changes lead to reduced oxygen delivery to photoreceptors and the retinal pigment epithelium (RPE) and contribute to the pathology of age-related macular degeneration (AMD). The implication of hypoxia-inducible factors (HIFs) in this process makes them good candidates as therapeutic targets for AMD. We developed a multiplex dual-acting therapy utilizing the shRNAmir system, delivered by a single adeno-associated virus, that reduces mRNA levels of Hif1a in photoreceptors and Hif2a in the RPE. This RNA interference (RNAi)-based strategy demonstrated a strong therapeutic effect, potently preserving photoreceptors and the RPE in two models of pseudo- and true hypoxia up to 61 weeks post-injection. The efficacy of our dual-acting virus proved superior to single-acting viruses targeting only Hif1a in photoreceptors or Hif2a in the RPE. By targeting a common, conserved disease pathway, this gene-agnostic RNAi therapy shows significant potential to protect tissues from chronic hypoxic insults in complex diseases such as AMD.

Indexed as

Basic Helix-Loop-Helix ProteinsHypoxia-Inducible Factor 1, alpha SubunitMacular DegenerationRNA InterferenceRNAi TherapeuticsAnimalsDependovirusDisease Models, AnimalEndothelial PAS Domain-Containing Protein 1Genetic TherapyGenetic VectorsHumansMiceRetinal Pigment EpitheliumRNA, Small InterferingBasic Helix-Loop-Helix ProteinsEndothelial PAS Domain-Containing Protein 1Hypoxia-Inducible Factor 1, alpha SubunitRNA, Small InterferingAAVage-related macular degenerationcell-specific RNA interferencegene therapyHIF1HIF2hypoxiamultiplex RNAiphotoreceptorretinal degenerationretinal pigment epithelium

Identifiers

PMID41017154
PMCPMC12925775

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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.