ArticleBlood2014
Computationally designed liver-specific transcriptional modules and hyperactive factor IX improve hepatic gene therapy.
Article in Blood, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 52 papers.
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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.
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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.
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Who cites it
52 citing papers in PubMed, 80 citations in OpenAlex.
- Gene therapy with adeno-associated virus vector 5-human factor IX in adults with hemophilia B.Blood · 2018Trial
- Increased gene therapy efficacy through the use of extended half-life clotting factors.Blood advances · 2026Article
- RNA-LNP-mediated in vivo prime editing corrects disease phenotypes in a mouse model of citrullinemia type I.Science translational medicine · 2026Article
- An analysis of attitudes toward gene therapy in people with severe hemophilia in Germany, a survey-based cross-sectional study.Therapeutic advances in hematology · 2026Article
- Genetic tools for imaging microcirculation via plasma labeling.Anatomical science international · 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
- Towards enhancing photostability and adeno-associated viral vector delivery for genetically encoded plasma fluorescent labels.Neurophotonics · 2025Article
- Use of an oversized AAV8 vector for CPS1 deficiency results in long-term survival and ammonia control.Molecular therapy. Nucleic acids · 2025Article
- Enhancing hemophilia A gene therapy by strategic F8 deletions in AAV vectors.Blood science (Baltimore, Md.) · 2025Article
- Comprehensive analysis of off-target and on-target effects resulting from liver-directed CRISPR-Cas9-mediated gene targeting with AAV vectors.Molecular therapy. Methods & clinical development · 2024Article
- Continuous directed evolution of a compact CjCas9 variant with broad PAM compatibility.Nature chemical biology · 2024Article
- State-of-the-art 2023 on gene therapy for phenylketonuria.Journal of inherited metabolic disease · 2024Review
- Predicting prime editing efficiency and product purity by deep learning.Nature biotechnology · 2023Article
- Intrabiliary infusion of naked DNA vectors targets periportal hepatocytes in mice.Molecular therapy. Methods & clinical development · 2022Article
- Liver-secreted fluorescent blood plasma markers enable chronic imaging of the microcirculation.Cell reports methods · 2022Article
- In vivo prime editing of a metabolic liver disease in mice.Science translational medicine · 2022Article
- Delivery of non-viral naked DNA vectors to liver in small weaned pigs by hydrodynamic retrograde intrabiliary injection.Molecular therapy. Methods & clinical development · 2022Article
- Optimization of miR-22 expression cassette for rAAV delivery on diabetes.Molecular biomedicine · 2022Article
- Article
- Development of Covalent Chitosan-Polyethylenimine Derivatives as Gene Delivery Vehicle: Synthesis, Characterization, and Evaluation.International journal of molecular sciences · 2021Article
Corrections and comments
- Commented on by
- Erratum issuedDosage error in article text
Authors and funding
12 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The development of the next-generation gene therapy vectors for hemophilia requires using lower and thus potentially safer vector doses and augmenting their therapeutic efficacy. We have identified hepatocyte-specific transcriptional cis-regulatory modules (CRMs) by using a computational strategy that increased factor IX (FIX) levels 11- to 15-fold. Vector efficacy could be enhanced by combining these hepatocyte-specific CRMs with a synthetic codon-optimized hyperfunctional FIX-R338L Padua transgene. This Padua mutation boosted FIX activity up to sevenfold, with no apparent increase in thrombotic risk. We then validated this combination approach using self-complementary adenoassociated virus serotype 9 (scAAV9) vectors in hemophilia B mice. This resulted in sustained supraphysiologic FIX activity (400%), correction of the bleeding diathesis at clinically relevant, low vector doses (5 × 10(10) vector genomes [vg]/kg) that are considered safe in patients undergoing gene therapy. Moreover, immune tolerance could be induced that precluded induction of inhibitory antibodies to FIX upon immunization with recombinant FIX protein.
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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.