Evidence map›Paper›PMID 42701144›Full record

ArticleGene therapy2026

Culture media alter retinal organoid physiology promoting AAV transduction and retinal ganglion cell survival.

Michelle O'Hara-Wright, Benjamin Y Lim, Melissa M Mangala, Vivienne Kaiser, Emilie Wong, Deborah Aubin, Victoria Nemeruck, Hallur Reynisson, Fatemeh Doroudian, Otilia P Y Chan and 6 more

Abstract read
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In one paragraph

Article in Gene therapy, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing 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

0 citing papers in PubMed.

No citing paper in PubMed yet.

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

16 authors.

Michelle O'Hara-Wright *Stem Cell Medicine Unit, Children's Medical Research Institute, University of Sydney, Westmead, 2145, NSW, Australia.
Benjamin Y Lim *Stem Cell Medicine Unit, Children's Medical Research Institute, University of Sydney, Westmead, 2145, NSW, Australia.ORCID http://orcid.org/0000-0002-7485-5672
Melissa M MangalaStem Cell Medicine Unit, Children's Medical Research Institute, University of Sydney, Westmead, 2145, NSW, Australia.
Vivienne KaiserStem Cell Medicine Unit, Children's Medical Research Institute, University of Sydney, Westmead, 2145, NSW, Australia.ORCID http://orcid.org/0009-0004-9227-9383
Emilie WongStem Cell Medicine Unit, Children's Medical Research Institute, University of Sydney, Westmead, 2145, NSW, Australia.
Deborah AubinStem Cell Medicine Unit, Children's Medical Research Institute, University of Sydney, Westmead, 2145, NSW, Australia.
Victoria NemeruckStem Cell Medicine Unit, Children's Medical Research Institute, University of Sydney, Westmead, 2145, NSW, Australia.
Hallur ReynissonInstitute for Photonics and Optical Sciences (IPOS), School of Physics, The University of Sydney, Camperdown, 2006, NSW, Australia.
Fatemeh DoroudianGene Therapy Unit, Children's Medical Research Institute, University of Sydney, Westmead, 2145, NSW, Australia.
Otilia P Y ChanGene Therapy Unit, Children's Medical Research Institute, University of Sydney, Westmead, 2145, NSW, Australia.
Nader AryamaneshSchool of Medical Sciences, Faculty of Medicine and Health, University of Sydney, Camperdown, 2006, NSW, Australia.ORCID http://orcid.org/0000-0003-4666-9175
Joao A PauloDepartment of Cell Biology, Blavatnik Institute, Harvard Medical School, Boston, MA, 02115, USA.
Stefano PalombaInstitute for Photonics and Optical Sciences (IPOS), School of Physics, The University of Sydney, Camperdown, 2006, NSW, Australia.
Mehdi MirzaeiMacquarie Medical School, Faculty of Medicine, Health and Human Sciences, Macquarie University, Sydney, NSW, Australia.
Samantha L GinnSchool of Medical Sciences, Faculty of Medicine and Health, University of Sydney, Camperdown, 2006, NSW, Australia.
Anai Gonzalez-CorderoStem Cell Medicine Unit, Children's Medical Research Institute, University of Sydney, Westmead, 2145, NSW, Australia. agonzalez-cordero@cmri.org.au.ORCID http://orcid.org/0000-0002-1818-0375

Funding

Australian National Health and Medical Research Council (NHMRC) 2022/GNT2021208Medical Research Future Fund Stem Cell Mission MRF2008912
6 · The paper itself

Abstract

Human iPSC-derived retinal organoids offer a human-relevant platform for inherited retinal disease (IRD) gene therapy, yet robust AAV transduction in vitro remains challenging. Here we show that culture in BrainPhys™ (BP) medium markedly enhances AAV-mediated gene delivery. Brief BP exposure during the transduction window improves uptake, whereas continuous BP culture yields the strongest effects, indicating contributions from acute entry processes and longer-term cellular remodelling. Quantitative proteomics reveal coordinated upregulation of viral entry and trafficking mediators, including integrins that form αVβ5, and the trans-Golgi entry factor GPR108, together with enrichment of endosomal/ER-Golgi transport proteins, providing a mechanistic basis for enhanced vector processing. BP concurrently promotes neuronal maturation and metabolism, with pronounced increases in neurotrophic and synaptic proteins and broad enhancement of oxidative phosphorylation components. Functional calcium imaging demonstrates comparable neuronal dynamics across conditions but reveals robust, recurrent network-level bursts under BP, consistent with strengthened connectivity. BP also preserves retinal ganglion cells and maintains expression of canonical markers, aligning with a BDNF-centred interactome and improved circuit integration. Collectively, these findings identify the culture environment as a critical determinant of AAV efficacy in human retinal tissue models and position BP as a simple, scalable strategy to reduce vector requirements, enhance retinal cells targeting, and increase the fidelity of organoid-based non-animal testing for IRD gene therapy development.

Identifiers

PMID42701144

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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.