ArticleMolecular therapy. Methods & clinical development2023
Characterization of the humanized FRG mouse model and development of an AAV-LK03 variant with improved liver lobular biodistribution.
Article in Molecular therapy. Methods & clinical development, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed.
- Liver-directed gene therapy results in amelioration of progressive familial intrahepatic cholestasis type 2 in mice.Hepatology communications · 2026Article
- Trends in the Engineering of Adeno-Associated Virus (AAV) for Precision Gene Delivery to the Central Nervous System (CNS).International journal of molecular sciences · 2026Review
- Engineering novel AAV capsids by broadly attenuated and subsequent muscle-specific tropism in mice and NHPs.Molecular therapy. Advances · 2026Article
- Advances and perspectives in animal models of human hepatitis A virus.Animal models and experimental medicine · 2026Review
- Screening of Single-Domain Antibodies to Adeno-Associated Viruses with Cross-Serotype Specificity and a Wide pH Tolerance.Viruses · 2025Article
- Serum factors create species-specific barriers to hepatic gene transfer by lipid nanoparticles in liver-humanized mice.Molecular therapy. Methods & clinical development · 2025Article
- 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
- Correlation of antigen expression with epigenetic modifications after rAAV delivery of a human factor IX variant in mice and rhesus macaques.Molecular therapy : the journal of the American Society of Gene Therapy · 2024Article
- Harnessing whole human liver ex situ normothermic perfusion for preclinical AAV vector evaluation.Nature communications · 2024Article
- Development of CNS tropic AAV1-like variants with reduced liver-targeting following systemic administration in mice.Molecular therapy : the journal of the American Society of Gene Therapy · 2024Article
- Efficient and safe therapeutic use of paired Cas9-nickases for primary hyperoxaluria type 1.EMBO molecular medicine · 2024Article
- Selection of appropriate non-clinical animal models to ensure translatability of novel AAV-gene therapies to the clinic.Gene therapy · 2024Review
- Gene therapy for urea cycle defects: An update from historical perspectives to future prospects.Journal of inherited metabolic disease · 2024Review
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Authors and funding
15 authors.
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Abstract
Recent clinical successes have intensified interest in using adeno-associated virus (AAV) vectors for therapeutic gene delivery. The liver is a key clinical target, given its critical physiological functions and involvement in a wide range of genetic diseases. In the present study, we first investigated the validity of a liver xenograft mouse model repopulated with primary hepatocytes using single-nucleus RNA sequencing (sn-RNA-seq) by studying the transcriptomic profile of human hepatocytes pre- and post-engraftment. Complementary immunofluorescence analyses performed in highly engrafted animals confirmed that the human hepatocytes organize and present appropriate patterns of zone-dependent enzyme expression in this model. Next, we tested a set of rationally designed HSPG de-targeted AAV-LK03 variants for relative transduction performance in human hepatocytes. We used immunofluorescence, next-generation sequencing, and single-nucleus transcriptomics data from highly engrafted FRG mice to demonstrate that the optimally HSPG de-targeted AAV-LK03 displayed a significantly improved lobular transduction profile in this model.
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