ArticleHuman gene therapy2013
Adeno-associated virus serotype 8 gene therapy leads to significant lowering of plasma cholesterol levels in humanized mouse models of homozygous and heterozygous familial hypercholesterolemia.
Article in Human gene therapy, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers, 1 of them a synthesis that pooled it.
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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
38 citing papers in PubMed, 1 synthesis or guideline pooled it, 72 citations in OpenAlex.
- The promising novel therapies for familial hypercholesterolemia.Journal of clinical laboratory analysis · 2022Pooled it
- Gene therapy and genome editing for lipoprotein disorders.European heart journal · 2025Review
- Established and Emerging Nucleic Acid Therapies for Familial Hypercholesterolemia.Circulation · 2024Review
- Review
- Review
- The Functional Role of Lipoproteins in Atherosclerosis: Novel Directions for Diagnosis and Targeting Therapy.Aging and disease · 2022Review
- MMAB promotes negative feedback control of cholesterol homeostasis.Nature communications · 2021Article
- Developing a second-generation clinical candidate AAV vector for gene therapy of familial hypercholesterolemia.Molecular therapy. Methods & clinical development · 2021Article
- Focus on the Lymphatic Route to Optimize Drug Delivery in Cardiovascular Medicine.Pharmaceutics · 2021Review
- Management of Familial Hypercholesterolemia: Current Status and Future Perspectives.Journal of the Endocrine Society · 2021Review
- Article
- AAV8 Gene Therapy for Crigler-Najjar Syndrome in Macaques Elicited Transgene T Cell Responses That Are Resident to the Liver.Molecular therapy. Methods & clinical development · 2018Article
- Familial Hypercholesterolemia: New Horizons for Diagnosis and Effective Management.Frontiers in pharmacology · 2018Review
- Nuclease-Mediated Gene Therapies for Inherited Metabolic Diseases of the Liver.The Yale journal of biology and medicine · 2017Review
- CRISPR Correction of a Homozygous Low-Density Lipoprotein Receptor Mutation in Familial Hypercholesterolemia Induced Pluripotent Stem Cells.Hepatology communications · 2017Article
- A human APOC3 missense variant and monoclonal antibody accelerate apoC-III clearance and lower triglyceride-rich lipoprotein levels.Nature medicine · 2017Article
- Somatic genome editing with CRISPR/Cas9 generates and corrects a metabolic disease.Scientific reports · 2017Article
- Non-Clinical Study Examining AAV8.TBG.hLDLR Vector-Associated Toxicity in Chow-Fed Wild-Type and LDLRHuman gene therapy. Clinical development · 2017Article
- Nonclinical Pharmacology/Toxicology Study of AAV8.TBG.mLDLR and AAV8.TBG.hLDLR in a Mouse Model of Homozygous Familial Hypercholesterolemia.Human gene therapy. Clinical development · 2017Article
- Episomal Nonviral Gene Therapy Vectors Slow Progression of Atherosclerosis in a Model of Familial Hypercholesterolemia.Molecular therapy. Nucleic acids · 2016Article
Corrections and comments
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Authors and funding
9 authors at 2 institutions in 1 country.
Funding
Abstract
Familial hypercholesterolemia (FH) is a life-threatening genetic disease caused by mutations in the gene encoding low-density lipoprotein receptor (LDLR). As a bridge to clinical trials, we generated a "humanized" mouse model lacking LDLR and apolipoprotein B (ApoB) mRNA editing catalytic polypeptide-1 (APOBEC-1) expression and expressing a human ApoB100 transgene in order to permit more authentic simulation of in vivo interactions between the clinical transgene product, human LDLR (hLDLR), and its endogenous ligand, human ApoB100. On a chow diet, the humanized LDLR-deficient mice have substantial hypercholesterolemia and a lipoprotein phenotype more closely resembling human homozygous FH (hoFH) than in previous mouse models of FH. On injection of an adeno-associated virus serotype 8 (AAV8) vector encoding the human LDLR cDNA, significant correction of hypercholesterolemia was realized at doses as low as 1.5 × 10(11) genome copies (GC)/kg. Given that some patients with heterozygous FH (heFH) cannot be adequately treated with current therapy, we then extended our studies to similarly "humanized" mice that were heterozygous for LDLR deficiency, and that have a lipoprotein phenotype resembling heterozygous FH. Injection of AAV8-hLDLR brought about significant reduction in total and LDL cholesterol at doses as low as 5 × 10(11) GC/kg. Collectively, these data demonstrate the safety and efficacy of the liver-specific AAV8-hLDLR vector in the treatment of humanized mice modeling both hoFH and heFH.
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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.