ArticleMolecular therapy. Methods & clinical development2019
AAV Gene Transfer with Tandem Promoter Design Prevents Anti-transgene Immunity and Provides Persistent Efficacy in Neonate Pompe Mice.
Article in Molecular therapy. Methods & clinical development, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 52 papers, 1 of them a synthesis that pooled it.
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Who cites it
52 citing papers in PubMed, 1 synthesis or guideline pooled it, 71 citations in OpenAlex.
- What's new and what's next for gene therapy in Pompe disease?Expert opinion on biological therapy · 2022Pooled it
- GAA engineered to improve cellular uptake enhances correction in a preclinical hematopoietic stem cell gene therapy model of Pompe disease.Molecular therapy. Advances · 2026Article
- A Comprehensive Update on Pompe Disease: From Existing Therapies to Emerging Curative Strategies.International journal of molecular sciences · 2026Review
- Identification of alterations of immunometabolism associated with Pompe disease.Cellular and molecular life sciences : CMLS · 2026Article
- Novel promoters drive therapeutic transgene expression and evade transgene-specific immune responses in a mouse model of Pompe disease.Molecular genetics and metabolism · 2026Article
- Review
- Evaluation of AAV vectors with tissue-specific or ubiquitous promoters in a mouse model of mucopolysaccharidosis type IVA.Molecular therapy. Methods & clinical development · 2025Article
- A myotropic AAV vector combined with skeletal muscleMolecular therapy. Methods & clinical development · 2025Article
- Current clinical applications of AAV-mediated gene therapy.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Review
- Rat models of musculoskeletal lysosomal storage disorders and their role in pre-clinical evaluation of gene therapy approaches.Mammalian genome : official journal of the International Mammalian Genome Society · 2025Review
- The combination of rAAV pseudo-lipid nanoparticle and triamcinolone acetonide enables multi-administration to liver.Molecular therapy. Methods & clinical development · 2025Article
- Management of Pompe disease alongside and beyond ERT: a narrative review.Acta myologica : myopathies and cardiomyopathies : official journal of the Mediterranean Society of Myology · 2025Review
- Preclinical lentiviral hematopoietic stem cell gene therapy corrects Pompe disease-related muscle and neurological manifestations.Molecular therapy : the journal of the American Society of Gene Therapy · 2024Article
- Synergism of dual AAV gene therapy and rapamycin rescues GSDIII phenotype in muscle and liver.JCI insight · 2024Article
- A functional mini-GDE transgene corrects impairment in models of glycogen storage disease type III.The Journal of clinical investigation · 2024Article
- Gene therapy for glycogen storage diseases.Journal of inherited metabolic disease · 2024Review
- AAV-mediated delivery of secreted acid α-glucosidase with enhanced uptake corrects neuromuscular pathology in Pompe mice.JCI insight · 2023Article
- Site-specific transgene integration in chimeric antigen receptor (CAR) T cell therapies.Biomarker research · 2023Review
- Suppression of pullulanase-induced cytotoxic T cell response with a dual promoter in GSD IIIa mice.JCI insight · 2022Article
- In vivo lentiviral vector gene therapy to cure hereditary tyrosinemia type 1 and prevent development of precancerous and cancerous lesions.Nature communications · 2022Article
Corrections and comments
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Authors and funding
15 authors at 4 institutions in 2 countries.
Funding
Abstract
Hepatocyte-restricted, AAV-mediated gene transfer is being used to provide sustained, tolerogenic transgene expression in gene therapy. However, given the episomal status of the AAV genome, this approach cannot be applied to pediatric disorders when hepatocyte proliferation may result in significant loss of therapeutic efficacy over time. In addition, many multi-systemic diseases require widespread expression of the therapeutic transgene that, when provided with ubiquitous or tissue-specific non-hepatic promoters, often results in anti-transgene immunity. Here we have developed tandem promoter monocistronic expression cassettes that, packaged in a single AAV, provide combined hepatic and extra-hepatic tissue-specific transgene expression and prevent anti-transgene immunity. We validated our approach in infantile Pompe disease, a prototype disease caused by lack of the ubiquitous enzyme acid-alpha-glucosidase (GAA), presenting multi-systemic manifestations and detrimental anti-GAA immunity. We showed that the use of efficient tandem promoters prevents immune responses to GAA following systemic AAV gene transfer in immunocompetent Gaa-/- mice. Then we demonstrated that neonatal gene therapy with either AAV8 or AAV9 in Gaa-/- mice resulted in persistent therapeutic efficacy when using a tandem liver-muscle promoter (LiMP) that provided high and persistent transgene expression in non-dividing extra-hepatic tissues. In conclusion, the tandem promoter design overcomes important limitations of AAV-mediated gene transfer and can be beneficial when treating pediatric conditions requiring persistent multi-systemic transgene expression and prevention of anti-transgene immunity.
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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.