ArticleClinical and translational medicine2020
The novel llama-human chimeric antibody has potent effect in lowering LDL-c levels in hPCSK9 transgenic rats.
Article in Clinical and translational medicine, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 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
9 citing papers in PubMed, 1 synthesis or guideline pooled it, 14 citations in OpenAlex.
- Research Progress and Applications of Multivalent, Multispecific and Modified Nanobodies for Disease Treatment.Frontiers in immunology · 2021Pooled it
- Engineered probiotic ameliorates hyperlipidemia and atherosclerosis by secreting PCSK9 nanobodies and regulating gut microbiota.Bioengineering & translational medicine · 2025Article
- Evolocumab Reduces Oxidative Stress and Lipid Peroxidation in Obese Zucker Rats.Pathophysiology : the official journal of the International Society for Pathophysiology · 2025Article
- Biparatopic anti-PCSK9 antibody enhances the LDL-uptake in HepG2 cells.Scientific reports · 2024Article
- Novel bispecific nanobody mitigates experimental intestinal inflammation in mice by targeting TNF-α and IL-23p19 bioactivities.Clinical and translational medicine · 2024Article
- An anti-CTLA-4 heavy chain-only antibody with enhanced TProceedings of the National Academy of Sciences of the United States of America · 2022Article
- Development and characterization of a camelid derived antibody targeting a linear epitope in the hinge domain of human PCSK9 protein.Scientific reports · 2022Article
- A novel nanobody-heavy chain antibody against Angiopoietin-like protein 3 reduces plasma lipids and relieves nonalcoholic fatty liver disease.Journal of nanobiotechnology · 2022Article
- Exploring cellular biochemistry with nanobodies.The Journal of biological chemistry · 2020Review
Corrections and comments
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Authors and funding
15 authors at 2 institutions in 2 countries.
Funding
Abstract
backgroundThe advent of proprotein convertase subtilisin/kexin type 9 (PCSK9)-inhibiting drugs have provided an effective, but extremely expensive treatment for the management of low density lipoprotein (LDL). Our aim was to explore a cost-effective application of camelid anti-PCSK9 single domain antibodies (sdAbs), which are high variable regions of the camelid heavy chain antibodies (VHHs), as a human PCSK9 (hPCSK9) inhibitor. One female llama was immunized with hPCSK9. Screening of high affinity anti-PCSK9 VHHs was carried out based on surface plasmon resonance (SPR) technology. We reported a lysate kinetic analysis method improving the screening efficiency. To increase the serum half-life and targeting properties, the constant region fragment of the human immunoglobulin gamma sub-type 4 (IgG4 Fc) was incorporated to form a novel llama-human chimeric molecule (VHH-hFc).
resultsThe PCSK9 inhibiting effects of the VHH proteins were analyzed in two human liver hepatocellular cells (HepG2 and Huh7) and in the hPCSK9 transgenic Sprague-Dawley (SD) rat model. The hPCSK9 antagonistic potency of the bivalent VHH-hFc exceeded the monovalent VHH (P < 0.001) in hepatocarcinoma cells. Furthermore, the llama-human chimeric VHH-Fc protein had a similar reduction (~ 40%) of the LDL-c and total cholesterol when compared to the approved evolocumab in transgenic SD rat model, but with low cost. More surprisingly, the chimeric heavy chain antibodies could be persevered for 3 months at room temperature with little loss of the affinity.
conclusionsDue to the high yield and low cost of Pichia pastoris, lipid-lowering effect and strong stability, the llama-human chimeric antibody (VHH-Fc) offers a potent therapeutic candidate for the control of the serum lipid level.
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Registered trials
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