ArticleJournal of controlled release : official journal of the Controlled Release Society2018
Fusion of fibroblast growth factor 21 to a thermally responsive biopolymer forms an injectable depot with sustained anti-diabetic action.
Article in Journal of controlled release : official journal of the Controlled Release Society, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
22 citing papers in PubMed, 56 citations in OpenAlex.
- Advances in engineering and applications of synthetic phase-separated membraneless organelles in biotechnology.Synthetic and systems biotechnology · 2026Review
- A unimolecular GLP-1 and FGF21 dual agonist for treatment of metabolic dysfunction-associated steatohepatitis.Communications medicine · 2026Article
- Biomimetic peptide conjugates as emerging strategies for controlled release from protein-based materials.Drug delivery · 2025Review
- Controlling Release Kinetics of an Adjuvant from a Depot Improves the Efficacy of Local Immunotherapy in Metastatic Cancer.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- A Novel Recombinant Human FGF21 Analog with High Glycosylation Has a Prolonged Half-Life and Affects Glycemic and Body Weight Control.International journal of molecular sciences · 2025Article
- Programmability and biomedical utility of intrinsically-disordered protein polymers.Advanced drug delivery reviews · 2024Review
- Synthetic intrinsically disordered protein fusion tags that enhance protein solubility.Nature communications · 2024Article
- The construction of elastin-like polypeptides and their applications in drug delivery system and tissue repair.Journal of nanobiotechnology · 2023Review
- A Review of Protein- and Peptide-Based Chemical Conjugates: Past, Present, and Future.Pharmaceutics · 2023Review
- Polyethylene Glycol-Like Brush Polymer Conjugate of a Protein Drug Does Not Induce an Antipolymer Immune Response and Has Enhanced Pharmacokinetics than Its Polyethylene Glycol Counterpart.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2022Article
- Intratumoral delivery of brachytherapy and immunotherapy by a thermally triggered polypeptide depot.Journal of controlled release : official journal of the Controlled Release Society · 2022Article
- Modulating the Thermoresponse of Polymer-Protein Conjugates with Hydrogels for Controlled Release.Polymers · 2021Article
- Sustained release of a GLP-1 and FGF21 dual agonist from an injectable depot protects mice from obesity and hyperglycemia.Science advances · 2020Article
- Engineering the Architecture of Elastin-Like Polypeptides: From Unimers to Hierarchical Self-Assembly.Advanced therapeutics · 2020Article
- The humanin peptide mediates ELP nanoassembly and protects human retinal pigment epithelial cells from oxidative stress.Nanomedicine : nanotechnology, biology, and medicine · 2020Article
- Recent trends in protein and peptide-based biomaterials for advanced drug delivery.Advanced drug delivery reviews · 2020Review
- Genomically informed small-molecule drugs overcome resistance to a sustained-release formulation of an engineered death receptor agonist in patient-derived tumor models.Science advances · 2019Article
- Thermoresponsive and Protease-Cleavable Interferon-Polypeptide Conjugates with Spatiotemporally Programmed Two-Step Release Kinetics for Tumor Therapy.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2019Article
- Conjugate of Doxorubicin to Albumin-Binding Peptide Outperforms Aldoxorubicin.Small (Weinheim an der Bergstrasse, Germany) · 2019Article
- Intra-vitreal αB crystallin fused to elastin-like polypeptide provides neuroprotection in a mouse model of age-related macular degeneration.Journal of controlled release : official journal of the Controlled Release Society · 2018Article
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
Fibroblast growth factor 21 (FGF21) is under investigation as a type 2 diabetes protein drug, but its efficacy is impeded by rapid in vivo clearance and by costly production methods. To improve the protein's therapeutic utility, we recombinantly expressed FGF21 as a fusion with an elastin-like polypeptide (ELP), a peptide polymer that exhibits reversible thermal phase behavior. Below a critical temperature, ELPs exist as miscible unimers, while above, they associate into a coacervate. The thermal responsiveness of ELPs is retained upon fusion to proteins, which has notable consequences for the production and in vivo delivery of FGF21. First, the ELP acts as a solubility enhancer during E. coli expression, yielding active fusion protein from the soluble cell lysate fraction and eliminating the protein refolding steps that are required for purification of FGF21 from inclusion bodies. Second, the ELP's phase transition behavior is exploited for facile chromatography-free purification of the ELP-FGF21 fusion. Third, the composition and molecular weight of the ELP are designed such that the ELP-FGF21 fusion undergoes a phase transition triggered solely by body heat, resulting in an immiscible viscous phase upon subcutaneous (s.c.) injection and thereby creating an injectable depot. Indeed, a single s.c. injection of ELP-FGF21 affords up to five days of sustained glycemic control in ob/ob mice. The ELP fusion partner massively streamlines production and purification of FGF21, while providing a controlled release method for delivery that reduces the frequency of injection, thereby enhancing the pharmacological properties of FGF21 as a protein drug to treat metabolic disease.
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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.