ArticlePlant biotechnology journal2013
Oral delivery of bioencapsulated exendin-4 expressed in chloroplasts lowers blood glucose level in mice and stimulates insulin secretion in beta-TC6 cells.
Article in Plant biotechnology journal, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 63 papers.
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Who cites it
63 citing papers in PubMed, 95 citations in OpenAlex.
- Bacteriophage P22 Virus-Like Particles as Nanoscale Protein Scaffolds for Plant Synthetic Biology.Plant biotechnology journal · 2026Article
- Oral probiotic delivery-based therapeutic strategies for inflammatory bowel disease.Asian journal of pharmaceutical sciences · 2026Review
- Engineering Marker-Free Lettuce Chloroplast Genome to Express Functional Glucagon-Like Peptide-1 Receptor Agonists Exenatide and Lixisenatide.Plant biotechnology journal · 2026Article
- Plant- and Microalgae-Based Biotechnological Strategies for Affordable and Non-Invasive Delivery of Antidiabetic Peptides.Pharmaceutics · 2026Review
- Accessible Type 2 diabetes medication through stable expression of Exendin-4 inFrontiers in systems biology · 2024Article
- Current Advancements on Oral Protein and Peptide Drug Delivery Approaches to Bioavailability: Extensive Review on Patents.Recent advances in drug delivery and formulation · 2024Review
- The lyophilized chloroplasts store synthetic DARPin G3 as bioactive encapsulated organelles.Journal of biological engineering · 2023Article
- Affordable oral proinsulin bioencapsulated in plant cells regulates blood sugar levels similar to natural insulin.Biomaterials · 2023Article
- Immunogenicity and contraceptive efficacy of plant-produced putative mouse-specific contraceptive peptides.Frontiers in plant science · 2023Article
- The strawberry-derived permeation enhancer pelargonidin enables oral protein delivery.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
- Current advances and future prospects in production of recombinant insulin and other proteins to treat diabetes mellitus.Biotechnology letters · 2022Review
- Insights into plastome ofSaudi journal of biological sciences · 2022Article
- Production of active Exendin-4 inFrontiers in plant science · 2022Article
- Seed- and leaf-based expression of FGF21-transferrin fusion proteins for oral delivery and treatment of non-alcoholic steatohepatitis.Frontiers in plant science · 2022Article
- Contributions of the international plant science community to the fight against infectious diseases in humans-part 2: Affordable drugs in edible plants for endemic and re-emerging diseases.Plant biotechnology journal · 2021Review
- Oral delivery of therapeutic proteins bioencapsulated in plant cells: preclinical and clinical advances.Current opinion in colloid & interface science · 2021Article
- Altered β-Cell Calcium Dynamics via Electric Field Exposure.Annals of biomedical engineering · 2021Article
- Plastid Transformation: How Does it Work? Can it Be Applied to Crops? What Can it Offer?International journal of molecular sciences · 2020Review
- Translocation from the chloroplast stroma into the thylakoid lumen allows expression of recombinant epidermal growth factor in transplastomic tobacco plants.Transgenic research · 2020Article
- Investigational new drug enabling angiotensin oral-delivery studies to attenuate pulmonary hypertension.Biomaterials · 2020Article
3 more citing papers are in PubMed but not listed here.
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
Glucagon-like peptide (GLP-1) increases insulin secretion but is rapidly degraded (half-life: 2 min in circulation). GLP-1 analogue, exenatide (Byetta) has a longer half-life (3.3-4 h) with potent insulinotropic effects but requires cold storage, daily abdominal injections with short shelf life. Because patients with diabetes take >60 000 injections in their life time, alternative delivery methods are highly desired. Exenatide is ideal for oral delivery because insulinotropism is glucose dependent, with reduced risk of hypoglycaemia even at higher doses. Therefore, exendin-4 (EX4) was expressed as a cholera toxin B subunit (CTB)-fusion protein in tobacco chloroplasts to facilitate bioencapsulation within plant cells and transmucosal delivery in the gut via GM1 receptors present in the intestinal epithelium. The transgene integration was confirmed by PCR and Southern blot analysis. Expression level of CTB-EX4 reached up to 14.3% of total leaf protein (TLP). Lyophilization of leaf material increased therapeutic protein concentration by 12- to 24-fold, extended their shelf life up to 15 months when stored at room temperature and eliminated microbes present in fresh leaves. The pentameric structure, disulphide bonds and functionality of CTB-EX4 were well preserved in lyophilized materials. Chloroplast-derived CTB-EX4 showed increased insulin secretion similar to the commercial EX4 in beta-TC6, a mouse pancreatic cell line. Even when 5000-fold excess dose of CTB-EX4 was orally delivered, it stimulated insulin secretion similar to the intraperitoneal injection of commercial EX4 but did not cause hypoglycaemia in mice. Oral delivery of the bioencapsulated EX4 should eliminate injections, increase patient compliance/convenience and significantly lower their cost.
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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.