ArticleGene therapy2011
Liver-specific microRNA-122 target sequences incorporated in AAV vectors efficiently inhibits transgene expression in the liver.
Article in Gene therapy, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 99 papers.
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Who cites it
99 citing papers in PubMed, 154 citations in OpenAlex.
- Clinical immunogenicity in rAAV gene therapy: Insights and implications.Molecular therapy. Advances · 2026Review
- Bone- and muscle-targeted adeno-associated viral vectors enable tissue-selective vitamin D receptor knockdown in mice.Gene therapy · 2026Article
- Challenging the more-is-better dogma: A precision-optimized AAV gene therapy for SMA.Molecular therapy : the journal of the American Society of Gene Therapy · 2026Article
- MicroRNA-based targeting strategies enable AAV-mediated, tissue-selective gene expression in adipose tissue and skeletal muscle of mice.Molecular therapy. Advances · 2026Article
- Molecular mechanisms in podocytopathies: finding suitable targets for a new era of glomerular gene therapy.Clinical kidney journal · 2026Review
- Molecular mechanisms limiting the AAV gene therapy treatment window in mouse models of blue cone monochromacy.Communications biology · 2025Article
- Dystrophin Restorative and Compensatory Gene Addition Therapies for Duchenne Muscular Dystrophy: Could CRISPRa Provide a Realistic Alternative?Muscles (Basel, Switzerland) · 2025Review
- Navigating the Hurdles of Intra-Articular AAV Gene Therapy.International journal of molecular sciences · 2025Review
- Trends and challenges of AAV-delivered gene editing therapeutics for CNS disorders: Implications for neurodegenerative disease.Molecular therapy. Nucleic acids · 2025Review
- Identification of a robust promoter in mouse and human hepatocytes by in vivo biopanning of a barcoded AAV library.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Article
- Article
- Mapping administration route-dependent transduction profiles of commonly used AAV variants in mice by barcode amplicon sequencing.Molecular therapy. Methods & clinical development · 2025Article
- Reducing off-target expression of mRNA therapeutics and vaccines in the liver with microRNA binding sites.Molecular therapy. Methods & clinical development · 2025Article
- Cardiac-Specific Gene Editing via an AAV9-Tnnt2-SaCas9-miR122TS Vector.Bio-protocol · 2025Article
- Molecular Mechanisms Limiting the Therapeutic Window of AAV Gene Therapy in Mouse Models of Blue Cone Monochromacy.bioRxiv : the preprint server for biology · 2025Article
- Optimized circular RNA vaccines for superior cancer immunotherapy.Theranostics · 2025Article
- The Intra-Articular Delivery of a Low-Dose Adeno-Associated Virus-IL-1 Receptor Antagonist Vector Alleviates the Progress of Arthritis in an Osteoarthritis Rat Model.Pharmaceutics · 2024Article
- Molecular Engineering of Virus Tropism.International journal of molecular sciences · 2024Review
- Targeted gene delivery systems for T-cell engineering.Cellular oncology (Dordrecht, Netherlands) · 2024Review
- Designing and optimizing AAV-mediated gene therapy for neurodegenerative diseases: from bench to bedside.Journal of translational medicine · 2024Review
39 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
8 authors at 1 institution in 1 country.
Funding
Abstract
Vectors based on adeno-associated virus (AAV) are effective in gene delivery in vivo. Tissue-specific gene expression is often needed to minimize ectopic expression in unintended cells and undesirable consequences. Here, we investigated whether incorporation of target sequences of tissue-specific microRNA (miRNA) into AAV vectors could inhibit ectopic expression in tissues such as the liver and hematopoietic cells. First we inserted liver-specific miR-122 target sequences (miR-122T) into the 3'-untranslated region (UTR) of a number of AAV vectors. After intravenous delivery in mice, we found that five copies of the 20mer miR-122T reduced liver expression of luciferase by 50-fold and β-galactosidase (LacZ) by 70-fold. Five copies of miR-122T also reduced mRNA levels of a secretable protein (myostatin propeptide) from the AAV vector plasmid by 23-fold in the liver. However, gene expression in other tissues, including the heart was not inhibited. Similarly, we inserted four copies of miR-142-3pT or miR-142-5pT, both hematopoietic lineage-specific, into the 3'-UTR of the AAV-luciferase vector. We wished to see whether they could prolong transgene expression by inhibiting expression in antigen-presenting cells. However, in vivo luciferase gene expression in major tissues declined with time, regardless of the miR-142 target sequences used. Quantitative analysis of the vector DNA in various tissues revealed that the decline of transgene expression in vivo was mainly because of promoter shut-off other than loss of AAV-transduced cells by immune destruction. Moreover, transgene expression was not detected in circulating mononuclear cells after delivering AAV9 vector with or without miR142T. These results demonstrate that liver-specific miR-122 target sequence in AAV vectors was highly efficient in reducing liver expression, whereas hematopoietic miR-142 target sequences were ineffective in preventing decline of AAV vector gene expression in nonhematopoietic tissues resulted from promoter shut-off.
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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.