Evidence map›Paper›PMID 42321174›Full record

ArticleNature communications2026

Safety and efficacy analysis of in vivo lentiviral gene therapy in pre-clinical ARC syndrome models.

Claudiu A Cozmescu, Mina Nazari, Loukia Touramanidou, Sonam Gurung, Dany Perocheau, Neil Sebire, Yi-Ting Hu, Sian Goldsworthy, Jemima J Burden, Youssef Khalil and 12 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Nature communications, 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

22 authors.

Claudiu A CozmescuNIHR Great Ormond Street Hospital Biomedical Research Centre, London, UK. claudiu.cozmescu.15@ucl.ac.uk.ORCID 0000-0003-1775-0265
Mina NazariNIHR Great Ormond Street Hospital Biomedical Research Centre, London, UK.
Loukia TouramanidouGreat Ormond Street Institute of Child Health, University College London, London, UK.
Sonam GurungGreat Ormond Street Institute of Child Health, University College London, London, UK.ORCID 0000-0003-3271-5273
Dany PerocheauGreat Ormond Street Institute of Child Health, University College London, London, UK.
Neil SebireNIHR Great Ormond Street Hospital Biomedical Research Centre, London, UK.
Yi-Ting HuGreat Ormond Street Institute of Child Health, University College London, London, UK.ORCID 0000-0001-8844-7779
Sian GoldsworthyGreat Ormond Street Institute of Child Health, University College London, London, UK.ORCID 0000-0002-9189-5617
Jemima J BurdenLaboratory for Molecular Cell Biology, University College London, London, UK.ORCID 0000-0001-5894-7043
Youssef KhalilGreat Ormond Street Institute of Child Health, University College London, London, UK.ORCID 0000-0001-9025-3017
Ivan DoykovNIHR Great Ormond Street Hospital Biomedical Research Centre, London, UK.
John R CounsellDivision of Surgery and Interventional Science, University College London; Royal Free Hospital, 9Th Floor (East), London, UK.ORCID 0000-0001-9208-101X
Rajvinder KardaEGA Institute for Women's Health, University College London, London, UK.ORCID 0000-0001-9821-483X
Sergi CastellanoGreat Ormond Street Institute of Child Health, University College London, London, UK.
Philippa MillsNIHR Great Ormond Street Hospital Biomedical Research Centre, London, UK.ORCID 0000-0002-9704-1268
Peter ClaytonNIHR Great Ormond Street Hospital Biomedical Research Centre, London, UK.
Wendy HeywoodNIHR Great Ormond Street Hospital Biomedical Research Centre, London, UK.ORCID 0000-0003-2106-8760
Dale MouldingNIHR Great Ormond Street Hospital Biomedical Research Centre, London, UK.ORCID 0000-0002-1431-7047
Simon N WaddingtonEGA Institute for Women's Health, University College London, London, UK.ORCID 0000-0003-4970-4730
Julien BaruteauNIHR Great Ormond Street Hospital Biomedical Research Centre, London, UK.ORCID 0000-0003-0582-540X
Giandomenico TurchianoGreat Ormond Street Institute of Child Health, University College London, London, UK.ORCID 0000-0001-9980-6810
Paul GissenNIHR Great Ormond Street Hospital Biomedical Research Centre, London, UK. p.gissen@ucl.ac.uk.ORCID 0000-0002-9712-6122

Funding

Great Ormond Street Hospital Charity (GOSH) V4420RCUK | Medical Research Council (MRC) MC_U12266B
6 · The paper itself

Abstract

Arthrogryposis, Renal dysfunction and Cholestasis (ARC) syndrome is a rare inherited disorder caused by defects in the VPS33B trafficking protein, leading to impaired bile flow, progressive liver disease and early death. No effective treatments are currently available. Gene therapy offers a potential approach by restoring the missing VPS33B protein in liver cells. Here, we show that liver-targeted lentiviral gene therapy safely and effectively rescues key features of ARC syndrome in a mouse model following in vivo administration by intravenous injection, combined with transient liver macrophage depletion. To assess the treatment efficacy, disease severity is exacerbated by 0.25% cholic acid diet feeds. A liver-specific vector shows a favourable safety profile over a ubiquitous vector. Mice receiving the safe liver-specific vector display improved survival, growth and liver function, reduced fibrosis and bile canaliculi restoration. These findings support targeted gene therapy as a promising treatment for ARC syndrome and related early-onset liver diseases.

Indexed as

ArthrogryposisCholestasisGenetic TherapyKidney DiseasesLentivirusAnimalsDisease Models, AnimalFemaleGenetic VectorsHumansLiverMaleMiceMice, Inbred C57BLRenal InsufficiencyVesicular Transport ProteinsVesicular Transport ProteinsVPS33B protein, human

Identifiers

PMID42321174
PMCPMC13282399

What OpenQuestion holds

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Registered trials

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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.