ArticleScience advances2021
Enhancement of liver-directed transgene expression at initial and repeat doses of AAV vectors admixed with ImmTOR nanoparticles.
Article in Science advances, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers, 1 of them a synthesis 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
30 citing papers in PubMed, 1 synthesis or guideline pooled it, 50 citations in OpenAlex.
- rAAV immunogenicity, toxicity, and durability in 255 clinical trials: A meta-analysis.Frontiers in immunology · 2022Pooled it
- Rapamycin nanoparticles mitigate anti-AAV antibody formation in a mouse model of ornithine transcarbamylase deficiency.Molecular therapy. Advances · 2026Article
- Nanoparticles targeting liver sinusoidal endothelial cells improve tolerance to vector and transgene antigens through tolerance spreading.Molecular therapy : the journal of the American Society of Gene Therapy · 2026Article
- Skeletal-muscle-targeted non-viral delivery of full-length DMD mRNA for Duchenne muscular dystrophy.Nature biomedical engineering · 2026Article
- Safety of Adeno-Associated Viral Vectors in Gene Therapy: Mechanisms of Toxicity, Clinical Risks, and Strategies for Their Minimization.International journal of molecular sciences · 2026Review
- Modulating nuclear stiffness and envelope barrier facilitates AAV nuclear entry and reduces immunogenicity.Nature communications · 2026Article
- Emerging Technologies Tackling Adeno-Associated Viruses (AAV) Immunogenicity in Gene Therapy Applications.Pharmaceutics · 2025Review
- ZNF146 accelerates lung adenocarcinoma progression through MDM2/p53 and PHGDH/ferroptosis.Cell & bioscience · 2025Article
- The deLIVERed promises of gene therapy: Past, present, and future of liver-directed gene therapy.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Review
- The curious case of AAV immunology.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Review
- Tolerization with a Novel Dual-Acting Liposomal Tim Agonist Prepares the Immune System for the Success of Gene Therapy.International journal of molecular sciences · 2025Article
- The combination of rAAV pseudo-lipid nanoparticle and triamcinolone acetonide enables multi-administration to liver.Molecular therapy. Methods & clinical development · 2025Article
- In Vivo Selection of S/MAR Sequences to Favour AAV Episomal Maintenance in Dividing Cells.International journal of molecular sciences · 2024Article
- Enhancing RNA-lipid nanoparticle delivery: Organ- and cell-specificity and barcoding strategies.Journal of controlled release : official journal of the Controlled Release Society · 2024Review
- Recombinant Adeno-Associated Virus Vectors for Gene Therapy of the Central Nervous System: Delivery Routes and Clinical Aspects.Biomedicines · 2024Review
- Role of FoxP3Human gene therapy · 2024Review
- Synergism of dual AAV gene therapy and rapamycin rescues GSDIII phenotype in muscle and liver.JCI insight · 2024Article
- Adeno-associated virus as a delivery vector for gene therapy of human diseases.Signal transduction and targeted therapy · 2024Review
- B cell focused transient immune suppression protocol for efficient AAV readministration to the liver.Molecular therapy. Methods & clinical development · 2024Article
- Readministration of high-dose adeno-associated virus gene therapy vectors enabled by ImmTOR nanoparticles combined with B cell-targeted agents.PNAS nexus · 2023Article
Corrections and comments
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Authors and funding
9 authors at 1 institution in 1 country.
Funding
Abstract
Systemic AAV (adeno-associated virus) gene therapy is a promising approach for the treatment of inborn errors of metabolism, but questions remain regarding its potency and durability. Tolerogenic ImmTOR nanoparticles encapsulating rapamycin have been shown to block the formation of neutralizing anti-capsid antibodies, thereby enabling vector re-administration. Here, we further demonstrate that ImmTOR admixed with AAV vectors also enhances hepatic transgene expression at the initial dose of AAV vector, independent of its effects on adaptive immunity. ImmTOR enhances AAV trafficking to the liver, resulting in increased hepatic vector copy numbers and transgene mRNA expression. Enhanced transgene expression occurs through a mechanism independent of the AAV receptor and cannot be replicated in vivo with free rapamycin or empty nanoparticles. The multipronged mechanism of ImmTOR action makes it an attractive candidate to enable more efficient transgene expression at first dose while simultaneously inhibiting adaptive responses against AAV to enable repeat dosing.
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.