ArticleHuman gene therapy2024
Have a Little Heart (or Not): Highly Minimized Skeletal Muscle Regulatory Cassettes with Low or No Activity in the Heart.
Article in Human gene therapy, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.
What it found
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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
4 citing papers in PubMed.
- AAV Vector Toolkit for the Delivery and Expression of the Artificial microRNA in the Murine Heart.Biotech (Basel (Switzerland)) · 2026Article
- MicroRNA-based targeting strategies enable AAV-mediated, tissue-selective gene expression in adipose tissue and skeletal muscle of mice.Molecular therapy. Advances · 2026Article
- All-in-one vectors for epigenetic CRISPR inhibition ofMolecular therapy. Methods & clinical development · 2025Article
- Systemic delivery of AAV5, AAV8, and AAV9 packaging a C5-12-microdystrophin-FLAG expression cassette in non-human primates.Molecular therapy. Methods & clinical development · 2025Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
3 authors.
Funding
Abstract
Adeno-associated virus-mediated gene therapies for certain muscle disorders require regulatory cassettes that provide high-level, striated muscle-specific activity. However, cardiotoxicity has emerged as a serious concern in clinical trials for Duchenne muscular dystrophy and X-linked myotubular myopathy. While this may be caused by systemic inflammatory effects of the treatment, high transgene expression in the heart may also play a role. Thus, certain muscle disorders may require a modulated level of therapeutic expression in the heart, while others may not require any cardiac expression at all. Additionally, the size of some cargos requires regulatory cassettes to be small enough that large cDNAs and other therapeutic payloads can be accommodated. Thus, we have performed enhancer/promoter optimization to develop highly minimized regulatory cassettes that are active in skeletal muscles, with either low or no detectable activity in cardiac muscle. Our No-heart (NH) cassette is active in most skeletal muscles, but exhibits only very low activity in extensor digitorum longus (EDL), soleus, and diaphragm, and no activity in the heart. By contrast, our Have a Little Heart (HLH) cassette displays high activity in most skeletal muscles, comparable to the ∼800-bp CK8 cassette, with increased activity in EDL, soleus, and diaphragm, and low activity in the heart. Due to their small size, these cassettes can be used in therapeutic strategies with both flexible (
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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.