ArticleMolecular therapy : the journal of the American Society of Gene Therapy2018
Bioengineered AAV Capsids with Combined High Human Liver Transduction In Vivo and Unique Humoral Seroreactivity.
Article in Molecular therapy : the journal of the American Society of Gene Therapy, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 117 papers, 1 of them a synthesis that pooled it.
What it found
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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.
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Who cites it
117 citing papers in PubMed, 1 synthesis or guideline pooled it, 160 citations in OpenAlex.
- AAV Gene Therapy Drug Development and Translation of Engineered Ocular and Neurotropic Capsids: A Systematic Review Using Natural Language Processing.Clinical and translational science · 2025Pooled it
- Increased gene therapy efficacy through the use of extended half-life clotting factors.Blood advances · 2026Article
- Functional editing of the OTC locus by targeted integration with phenotype correction and restoration of endogenous expression patterns.Molecular therapy : the journal of the American Society of Gene Therapy · 2026Article
- Delivery Systems for Therapeutic Genome Editing: Challenges, Innovations, and Future Perspectives.MedComm · 2026Review
- Translational Barriers to AAV and CRISPR Gene Therapy in Diabetes.Saudi medical journal · 2026Review
- Receptor-guided AAV Tropism Engineering via MATCH.bioRxiv : the preprint server for biology · 2026Article
- Review
- Review
- Species-specific AAVR dominates species-tropism of adeno-associated virus (AAV) vectors.Research square · 2025Article
- hafoe: an interactive tool for the analysis of chimeric AAV libraries after random mutagenesis.Gene therapy · 2025Article
- Scaling DNA engineering.Trends in biotechnology · 2025Review
- AAV for ovarian cancer gene therapy.Cancer gene therapy · 2025Review
- 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
- A comprehensive atlas of AAV tropism in the mouse.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Article
- Long-term inhibition of Hepatitis B virus gene expression by a primary microrna expressing ancestral adeno-associated viral vector.Virology journal · 2025Review
- AAVolve: Concatenated long-read deep sequencing enables whole capsid tracking during shuffled AAV library selection.Molecular therapy. Methods & clinical development · 2024Article
- Review
- Gene Therapy for Inherited Liver Disease: To Add or to Edit.International journal of molecular sciences · 2024Review
- Mice Engrafted with Human Liver Cells.Seminars in liver disease · 2024Review
- Enhanced AAV transduction across preclinical CNS models: A comparative study in human brain organoids with cross-species evaluations.Molecular therapy. Nucleic acids · 2024Article
57 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
21 authors at 8 institutions in 5 countries.
Funding
Abstract
Existing recombinant adeno-associated virus (rAAV) serotypes for delivering in vivo gene therapy treatments for human liver diseases have not yielded combined high-level human hepatocyte transduction and favorable humoral neutralization properties in diverse patient groups. Yet, these combined properties are important for therapeutic efficacy. To bioengineer capsids that exhibit both unique seroreactivity profiles and functionally transduce human hepatocytes at therapeutically relevant levels, we performed multiplexed sequential directed evolution screens using diverse capsid libraries in both primary human hepatocytes in vivo and with pooled human sera from thousands of patients. AAV libraries were subjected to five rounds of in vivo selection in xenografted mice with human livers to isolate an enriched human-hepatotropic library that was then used as input for a sequential on-bead screen against pooled human immunoglobulins. Evolved variants were vectorized and validated against existing hepatotropic serotypes. Two of the evolved AAV serotypes, NP40 and NP59, exhibited dramatically improved functional human hepatocyte transduction in vivo in xenografted mice with human livers, along with favorable human seroreactivity profiles, compared with existing serotypes. These novel capsids represent enhanced vector delivery systems for future human liver gene therapy applications.
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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.