ArticleNature medicine2021
Biodistribution of onasemnogene abeparvovec DNA, mRNA and SMN protein in human tissue.
Article in Nature medicine, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 68 papers, 1 of them a synthesis that pooled it.
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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.
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.
Who cites it
68 citing papers in PubMed, 1 synthesis or guideline pooled it, 99 citations in OpenAlex.
- Swallowing and feeding after disease-modifying treatment for spinal muscular atrophy: a systematic review of assessment modalities and outcomes.Orphanet journal of rare diseases · 2026Pooled it
- Intrathecal onasemnogene abeparvovec for treatment-experienced patients with spinal muscular atrophy: a phase 3b, open-label trial.Nature medicine · 2026Trial
- Onasemnogene abeparvovec for presymptomatic infants with two copies of SMN2 at risk for spinal muscular atrophy type 1: the Phase III SPR1NT trial.Nature medicine · 2022Trial
- Addressing the Global Disparities in Access to Treatment in Spinal Muscular Atrophy.Muscle & nerve · 2026Review
- Preclinical efficacy of a gene therapy forMolecular therapy. Advances · 2026Article
- Ten years of disease-modifying therapy in spinal muscular atrophy: lessons learned and future directions.Nature reviews. Neurology · 2026Review
- Lack of sensorimotor toxicity when using the clinical SMN expression cassette in scAAV9.Nature neuroscience · 2026Article
- Survival Motor Neuron Protein Requirement-Supply Mismatch in Spinal Muscular Atrophy: A Conceptual Framework.Advances in therapy · 2026Review
- Adeno-Associated Virus Gene Therapy for Spinal Muscular Atrophy Induces Hepatotoxicity via Cytokine and Macrophage Activation.Liver international : official journal of the International Association for the Study of the Liver · 2026Article
- Intravenous administration of an engineered AAV9-gene-silencing vector suppresses human SOD1 and extends survival in an ALS mouse model.Nature communications · 2026Article
- Onasemnogene Abeparvovec in Patients With SMA: Interim Results of the RESTORE Registry in Japan.Annals of clinical and translational neurology · 2026Article
- Engineering challenges and translational opportunities in emerging gene delivery platforms.Nature biomedical engineering · 2026Review
- Gene Targeted Therapies for Neurodegenerative Disorders: Strategies and Implications in ALS and SMA.Genes · 2026Review
- RNA biomarkers in spinal muscular atrophy: enhancing pathogenesis understanding and guiding precision medicine.Cellular and molecular life sciences : CMLS · 2026Review
- Preclinical evaluation of INS1201 AAV9-micro-dystrophin via CSF administration as a potential therapy for Duchenne muscular dystrophy.Molecular therapy. Advances · 2026Article
- AAV9 gene therapy optimization for SMARD1/CMT2S: safety and long-term efficacy comparison of two vectors in a SMARD1 preclinical model.Journal of biomedical science · 2026Article
- Spinal muscular atrophy in the disease-modifying therapy era: successes, limitations and future directions.Frontiers in molecular medicine · 2026Review
- Genetic therapies for neurological diseases.Pharmacological reviews · 2026Review
- Spinal muscular atrophy: Biology, pathogenesis, and therapeutic advances.Therapeutic advances in neurological disorders · 2026Review
- Directed evolution of liver-detargeted AAV vectors for systemic gene delivery to skeletal muscle and heart.Molecular therapy. Methods & clinical development · 2025Article
8 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
19 authors at 6 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Spinal muscular atrophy type 1 (SMA1) is a debilitating neurodegenerative disease resulting from survival motor neuron 1 gene (SMN1) deletion/mutation. Onasemnogene abeparvovec (formerly AVXS-101) is a gene therapy that restores SMN production via one-time systemic administration. The present study demonstrates widespread biodistribution of vector genomes and transgenes throughout the central nervous system (CNS) and peripheral organs, after intravenous administration of an AAV9-mediated gene therapy. Two symptomatic infants with SMA1 enrolled in phase III studies received onasemnogene abeparvovec. Both patients died of respiratory complications unrelated to onasemnogene abeparvovec. One patient had improved motor function and the other died shortly after administration before appreciable clinical benefit could be observed. In both patients, onasemnogene abeparvovec DNA and messenger RNA distribution were widespread among peripheral organs and in the CNS. The greatest concentration of vector genomes was detected in the liver, with an increase over that detected in CNS tissues of 300-1,000-fold. SMN protein, which was low in an untreated SMA1 control, was clearly detectable in motor neurons, brain, skeletal muscle and multiple peripheral organs in treated patients. These data support the fact that onasemnogene abeparvovec has effective distribution, transduction and expression throughout the CNS after intravenous administration and restores SMN expression in humans.
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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.