Evidence map›Paper›PMID 42177183›Full record

ArticleNature communications2026

Long-term comparative analysis of AAV9-mediated gene replacement therapies for spinal muscular atrophy in mice.

Xiupeng Chen, Qing Xie, Sarah J Nath, Mojiao Tang, Hong Ma, Yasemin Özgür Günes, Tapan Sharma, Hao Liu, Mengtian Cui, Ailing Du and 18 more

Abstract readComparative Study
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

28 authors.

Xiupeng ChenHorae Gene Therapy Center, Department of Genetic and Cellular Medicine, UMass Chan Medical School, Worcester, MA, USA.ORCID http://orcid.org/0000-0001-5916-3953
Qing XieHorae Gene Therapy Center, Department of Genetic and Cellular Medicine, UMass Chan Medical School, Worcester, MA, USA.
Sarah J NathHorae Gene Therapy Center, Department of Genetic and Cellular Medicine, UMass Chan Medical School, Worcester, MA, USA.
Mojiao TangHorae Gene Therapy Center, Department of Genetic and Cellular Medicine, UMass Chan Medical School, Worcester, MA, USA.
Hong MaHorae Gene Therapy Center, Department of Genetic and Cellular Medicine, UMass Chan Medical School, Worcester, MA, USA.
Yasemin Özgür GünesHorae Gene Therapy Center, Department of Genetic and Cellular Medicine, UMass Chan Medical School, Worcester, MA, USA.ORCID http://orcid.org/0000-0002-2112-127X
Tapan SharmaHorae Gene Therapy Center, Department of Genetic and Cellular Medicine, UMass Chan Medical School, Worcester, MA, USA.ORCID http://orcid.org/0000-0003-2495-2236
Hao LiuHorae Gene Therapy Center, Department of Genetic and Cellular Medicine, UMass Chan Medical School, Worcester, MA, USA.
Mengtian CuiHorae Gene Therapy Center, Department of Genetic and Cellular Medicine, UMass Chan Medical School, Worcester, MA, USA.
Ailing DuHorae Gene Therapy Center, Department of Genetic and Cellular Medicine, UMass Chan Medical School, Worcester, MA, USA.
Mengjia LuHorae Gene Therapy Center, Department of Genetic and Cellular Medicine, UMass Chan Medical School, Worcester, MA, USA.
Sophia Y LiuHorae Gene Therapy Center, Department of Genetic and Cellular Medicine, UMass Chan Medical School, Worcester, MA, USA.
Boonying WassamonHorae Gene Therapy Center, Department of Genetic and Cellular Medicine, UMass Chan Medical School, Worcester, MA, USA.
Mengyao XuHorae Gene Therapy Center, Department of Genetic and Cellular Medicine, UMass Chan Medical School, Worcester, MA, USA.ORCID http://orcid.org/0009-0001-2468-8941
Joseph Yunxi WuHorae Gene Therapy Center, Department of Genetic and Cellular Medicine, UMass Chan Medical School, Worcester, MA, USA.
Qin SuHorae Gene Therapy Center, Department of Genetic and Cellular Medicine, UMass Chan Medical School, Worcester, MA, USA.
Timothy P FitzgibbonsDivision of Cardiovascular Medicine, Department of Medicine, UMass Chan Medical School, Worcester, MA, USA.
Jinghua LiuHorae Gene Therapy Center, Department of Genetic and Cellular Medicine, UMass Chan Medical School, Worcester, MA, USA.
Fang WanHorae Gene Therapy Center, Department of Genetic and Cellular Medicine, UMass Chan Medical School, Worcester, MA, USA.
Veena KumananHorae Gene Therapy Center, Department of Genetic and Cellular Medicine, UMass Chan Medical School, Worcester, MA, USA.
Ran HeHorae Gene Therapy Center, Department of Genetic and Cellular Medicine, UMass Chan Medical School, Worcester, MA, USA.
Yijie MaCANbridge Pharmaceuticals, Burlington, MA, USA.
Jun YangCANbridge Pharmaceuticals, Burlington, MA, USA.
Heather L Gray-EdwardsHorae Gene Therapy Center, Department of Genetic and Cellular Medicine, UMass Chan Medical School, Worcester, MA, USA.ORCID http://orcid.org/0000-0002-7856-3159
Thomas L GallagherHorae Gene Therapy Center, Department of Genetic and Cellular Medicine, UMass Chan Medical School, Worcester, MA, USA.ORCID http://orcid.org/0000-0001-6381-6902
Phillip W L TaiHorae Gene Therapy Center, Department of Genetic and Cellular Medicine, UMass Chan Medical School, Worcester, MA, USA.ORCID http://orcid.org/0000-0001-7409-8344
Guangping GaoHorae Gene Therapy Center, Department of Genetic and Cellular Medicine, UMass Chan Medical School, Worcester, MA, USA. guangping.gao@umassmed.edu.ORCID http://orcid.org/0000-0003-0097-9012
Jun XieHorae Gene Therapy Center, Department of Genetic and Cellular Medicine, UMass Chan Medical School, Worcester, MA, USA. jun.xie@umassmed.edu.ORCID http://orcid.org/0000-0001-9565-1567

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Spinal muscular atrophy (SMA) results from a deficiency of the survival motor neuron (SMN) protein. Zolgensma, an adeno-associated virus (AAV)-based SMN1 gene-replacement therapy, is approved for SMA, though its long-term efficacy and safety remain uncertain. This study compares a Zolgensma-like benchmark vector with a 2nd-generation vector featuring a codon-optimized SMN1 transgene under the control of an endogenous SMN1 promoter. In SMA mice, intracerebroventricular delivery of the 2nd-generation vector improved survival and phenotypic outcomes compared with the benchmark. However, motor impairment was observed in wild-type mice 20 months post-injection with the 2nd-generation vector. Notably, cardiac thrombosis and hepatocellular carcinoma were associated with the benchmark vector, but not with the 2nd-generation vector. While AAV-related tumorigenesis appears to be species-specific to mice, these findings underscore the need for careful long‑term monitoring in patients treated with Zolgensma.

Indexed as

DependovirusGenetic TherapyGenetic VectorsMuscular Atrophy, SpinalSurvival of Motor Neuron 1 ProteinAnimalsCarcinoma, HepatocellularDisease Models, AnimalFemaleGene Therapy AgentsHumansLiver NeoplasmsMaleMiceMice, Inbred C57BLPromoter Regions, Geneticonasemnogene abeparvovecRecombinant Fusion ProteinsSmn1 protein, mouseSurvival of Motor Neuron 1 Protein

Identifiers

PMID42177183
PMCPMC13385853

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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.