ArticlePlant biotechnology journal2011
Low-cost production of proinsulin in tobacco and lettuce chloroplasts for injectable or oral delivery of functional insulin and C-peptide.
Article in Plant biotechnology journal, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 81 papers.
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Who cites it
81 citing papers in PubMed, 167 citations in OpenAlex.
- Trial
- Chloroplasts as ingredients for food: a review.Food & function · 2026Review
- Plant- and Microalgae-Based Biotechnological Strategies for Affordable and Non-Invasive Delivery of Antidiabetic Peptides.Pharmaceutics · 2026Review
- Transplastomic biofactory for the production of functional human α-lactalbumin for nutritional and therapeutic applications.Scientific reports · 2026Article
- Article
- Developing downstream processes for the purification of recombinant proteins and small molecules from Nicotiana benthamiana biomass.Plant biotechnology journal · 2026Review
- Monitoring the stability of transgene expression in lettuce using the RUBY reporter.Plant cell reports · 2025Article
- Engineering Camelina sativa Seeds as a Green Bioreactor for the Production of Affordable Human Pro-insulin that Demonstrates Anti-diabetic Efficacy in Rats.Molecular biotechnology · 2025Article
- Recent trends and advances in chloroplast engineering and transformation methods.Frontiers in plant science · 2025Review
- Construction and optimization of a genetic transformation system for efficient expression of human insulin-GFP fusion gene in flax.Bioresources and bioprocessing · 2024Article
- Delivery of biologics: Topical administration.Biomaterials · 2023Review
- Enterohemorrhagic Escherichia coli O157:H7 antigens produced in transgenic lettuce effective as an oral vaccine in mice.TAG. Theoretical and applied genetics. Theoretische und angewandte Genetik · 2023Article
- Affordable oral proinsulin bioencapsulated in plant cells regulates blood sugar levels similar to natural insulin.Biomaterials · 2023Article
- Soluble CD80 oral delivery by recombinant Lactococcus suppresses tumor growth by enhancing antitumor immunity.Bioengineering & translational medicine · 2023Article
- Review
- Genetic engineering of complex feed enzymes into barley seed for direct utilization in animal feedstuff.Plant biotechnology journal · 2023Article
- Recent advances in expression and purification strategies for plant made vaccines.Frontiers in plant science · 2023Review
- Current advances and future prospects in production of recombinant insulin and other proteins to treat diabetes mellitus.Biotechnology letters · 2022Review
- 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
21 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
2 authors at 1 institution in 1 country.
Funding
Abstract
Current treatment for type I diabetes includes delivery of insulin via injection or pump, which is highly invasive and expensive. The production of chloroplast-derived proinsulin should reduce cost and facilitate oral delivery. Therefore, tobacco and lettuce chloroplasts were transformed with the cholera toxin B subunit fused with human proinsulin (A, B, C peptides) containing three furin cleavage sites (CTB-PFx3). Transplastomic lines were confirmed for site-specific integration of transgene and homoplasmy. Old tobacco leaves accumulated proinsulin up to 47% of total leaf protein (TLP). Old lettuce leaves accumulated proinsulin up to 53% TLP. Accumulation was so stable that up to ~40% proinsulin in TLP was observed even in senescent and dried lettuce leaves, facilitating their processing and storage in the field. Based on the yield of only monomers and dimers of proinsulin (3 mg/g leaf, a significant underestimation), with a 50% loss of protein during the purification process, one acre of tobacco could yield up to 20 million daily doses of insulin per year. Proinsulin from tobacco leaves was purified up to 98% using metal affinity chromatography without any His-tag. Furin protease cleaved insulin peptides in vitro. Oral delivery of unprocessed proinsulin bioencapsulated in plant cells or injectable delivery into mice showed reduction in blood glucose levels similar to processed commercial insulin. C-peptide should aid in long-term treatment of diabetic complications including stimulation of nerve and renal functions. Hyper-expression of functional proinsulin and exceptional stability in dehydrated leaves offer a low-cost platform for oral and injectable delivery of cleavable proinsulin.
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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.