ArticleHuman molecular genetics2014
Morpholino antisense oligonucleotides targeting intronic repressor Element1 improve phenotype in SMA mouse models.
Article in Human molecular genetics, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 43 papers, 4 of them syntheses that pooled 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.
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
43 citing papers in PubMed, 4 syntheses or guidelines pooled it, 62 citations in OpenAlex.
- Systematic review and meta-analysis determining the benefits of in vivo genetic therapy in spinal muscular atrophy rodent models.Gene therapy · 2022Pooled it
- Alternative splicing and cancer: a systematic review.Signal transduction and targeted therapy · 2021Pooled it
- Drug treatment for spinal muscular atrophy types II and III.The Cochrane database of systematic reviews · 2020Pooled it
- Drug treatment for spinal muscular atrophy type I.The Cochrane database of systematic reviews · 2019Pooled it
- Morpholino-Mediated Exon Inclusion for Spinal Muscular Atrophy (SMA).Methods in molecular biology (Clifton, N.J.) · 2025Article
- Systemic Injection of Antisense Oligos into Spinal Muscular Atrophy (SMA) Mice and Evaluation.Methods in molecular biology (Clifton, N.J.) · 2025Article
- Recent Progress in Gene-Targeting Therapies for Spinal Muscular Atrophy: Promises and Challenges.Genes · 2024Review
- A combinatorial approach increases SMN level in SMA model mice.Human molecular genetics · 2022Article
- Spinal muscular atrophy: From approved therapies to future therapeutic targets for personalized medicine.Cell reports. Medicine · 2021Review
- TargetedBiomedicines · 2021Article
- RNA-Targeting Splicing Modifiers: Drug Development and Screening Assays.Molecules (Basel, Switzerland) · 2021Review
- Analysis of Putative Epigenetic Regulatory Elements in theInternational journal of molecular sciences · 2020Review
- Functional characterization of SMN evolution in mouse models of SMA.Scientific reports · 2019Article
- Blocking p62-dependent SMN degradation ameliorates spinal muscular atrophy disease phenotypes.The Journal of clinical investigation · 2018Article
- Antisense Oligonucleotide-Mediated Terminal Intron Retention of the SMN2 Transcript.Molecular therapy. Nucleic acids · 2018Article
- Modulation of nuclear REST by alternative splicing: a potential therapeutic target for Huntington's disease.Journal of cellular and molecular medicine · 2017Article
- How the discovery of ISS-N1 led to the first medical therapy for spinal muscular atrophy.Gene therapy · 2017Review
- Antisense Oligonucleotides: Translation from Mouse Models to Human Neurodegenerative Diseases.Neuron · 2017Review
- Efficient SMN Rescue following Subcutaneous Tricyclo-DNA Antisense Oligonucleotide Treatment.Molecular therapy. Nucleic acids · 2017Article
- Identification of a Peptide for Systemic Brain Delivery of a Morpholino Oligonucleotide in Mouse Models of Spinal Muscular Atrophy.Nucleic acid therapeutics · 2017Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
Spinal muscular atrophy (SMA) is a neurodegenerative disease caused by the loss of Survival Motor Neuron-1 (SMN1). In all SMA patients, a nearly identical copy gene called SMN2 is present, which produces low levels of functional protein owing to an alternative splicing event. To prevent exon-skipping, we have targeted an intronic repressor, Element1 (E1), located upstream of SMN2 exon 7 using Morpholino-based antisense oligonucleotides (E1(MO)-ASOs). A single intracerebroventricular injection in the relatively severe mouse model of SMA (SMNΔ7 mouse model) elicited a robust induction of SMN protein, and mean life span was extended from an average survival of 13 to 54 days following a single dose, consistent with large weight gains and a correction of the neuronal pathology. Additionally, E1(MO)-ASO treatment in an intermediate SMA mouse (SMN(RT) mouse model) significantly extended life span by ∼700% and weight gain was comparable with the unaffected animals. While a number of experimental therapeutics have targeted the ISS-N1 element of SMN2 pre-mRNA, the development of E1 ASOs provides a new molecular target for SMA therapeutics that dramatically extends survival in two important pre-clinical models of disease.
Indexed as
Identifiers
What OpenQuestion holds
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.