ArticleMolecular therapy : the journal of the American Society of Gene Therapy2010
Persistent expression of FLAG-tagged micro dystrophin in nonhuman primates following intramuscular and vascular delivery.
Article in Molecular therapy : the journal of the American Society of Gene Therapy, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to 2 registered trials, which are not on this map. Cited by 59 papers.
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.
Phase I Gene Transfer Clinical Trial for Duchenne Muscular Dystrophy Using rAAVrh74.MCK.Micro-dystrophin
Phase I/IIa Gene Transfer Clinical Trial for Duchenne Muscular Dystrophy Using rAAVrh74.MCK.GALGT2
Who cites it
59 citing papers in PubMed, 93 citations in OpenAlex.
- Sustained alpha-sarcoglycan gene expression after gene transfer in limb-girdle muscular dystrophy, type 2D.Annals of neurology · 2010Trial
- 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
- Article
- Expression and function of four AAV-based constructs for dystrophin restoration in the mdx mouse model of Duchenne muscular dystrophy.Biology open · 2023Article
- Translating musculoskeletal bioengineering into tissue regeneration therapies.Science translational medicine · 2022Review
- Therapeutic potential of highly functional codon-optimized microutrophin for muscle-specific expression.Scientific reports · 2022Article
- Lack of Toxicity in Nonhuman Primates Receiving Clinically Relevant Doses of an AAV9.U7snRNA Vector Designed to InduceHuman gene therapy · 2021Article
- Preclinical Systemic Delivery of Adeno-Associated α-Sarcoglycan Gene Transfer for Limb-Girdle Muscular Dystrophy.Human gene therapy · 2021Article
- Dose-Escalation Study of Systemically Delivered rAAVrh74.MHCK7.micro-dystrophin in theHuman gene therapy · 2021Article
- AAV8 locoregional delivery induces long-term expression of an immunogenic transgene in macaques despite persisting local inflammation.Molecular therapy. Methods & clinical development · 2021Article
- Adeno-Associated Virus (AAV)-Mediated Gene Therapy for Duchenne Muscular Dystrophy: The Issue of Transgene Persistence.Frontiers in neurology · 2021Review
- Of rAAV and Men: From Genetic Neuromuscular Disorder Efficacy and Toxicity Preclinical Studies to Clinical Trials and Back.Journal of personalized medicine · 2020Review
- Muscle-Directed Delivery of an AAV1 Vector Leads to Capsid-Specific T Cell Exhaustion in Nonhuman Primates and Humans.Molecular therapy : the journal of the American Society of Gene Therapy · 2020Article
- Gene Delivery for Limb-Girdle Muscular Dystrophy Type 2D by Isolated Limb Infusion.Human gene therapy · 2019Article
- Bridging from Intramuscular to Limb Perfusion Delivery of rAAV: Optimization in a Non-human Primate Study.Molecular therapy. Methods & clinical development · 2019Article
- CRISPR Correction of Duchenne Muscular Dystrophy.Annual review of medicine · 2019Review
- Gene Therapy for Heart Failure: New Perspectives.Current heart failure reports · 2018Review
- Systemic Delivery of Dysferlin Overlap Vectors Provides Long-Term Gene Expression and Functional Improvement for Dysferlinopathy.Human gene therapy · 2018Article
- Micro-Dystrophin Gene Therapy Goes Systemic in Duchenne Muscular Dystrophy Patients.Human gene therapy · 2018Article
- Effective regeneration of dystrophic muscle using autologous iPSC-derived progenitors with CRISPR-Cas9 mediated precise correction.Medical hypotheses · 2018Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
13 authors at 2 institutions in 1 country.
Funding
Abstract
Animal models for Duchenne muscular dystrophy (DMD) have species limitations related to assessing function, immune response, and distribution of micro- or mini-dystrophins. Nonhuman primates (NHPs) provide the ideal model to optimize vector delivery across a vascular barrier and provide accurate dose estimates for widespread transduction. To address vascular delivery and dosing in rhesus macaques, we have generated a fusion construct that encodes an eight amino-acid FLAG epitope at the C-terminus of micro-dystrophin to facilitate translational studies targeting DMD. Intramuscular (IM) injection of AAV8.MCK.micro-dys.FLAG in the tibialis anterior (TA) of macaques demonstrated robust gene expression, with muscle transduction (50-79%) persisting for up to 5 months. Success by IM injection was followed by targeted vascular delivery studies using a fluoroscopy-guided catheter threaded through the femoral artery. Three months after gene transfer, >80% of muscle fibers showed gene expression in the targeted muscle. No cellular immune response to AAV8 capsid, micro-dystrophin, or the FLAG tag was detected by interferon-gamma (IFN-gamma) enzyme-linked immunosorbent spot (ELISpot) at any time point with either route. In summary, an epitope-tagged micro-dystrophin cassette enhances the ability to evaluate site-specific localization and distribution of gene expression in the NHP in preparation for vascular delivery clinical trials.
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.