NIH grant: Production in maize of low-cost heat stable forms of GLP-1 and GIP receptor agonists for treatment of diabetes and obesity (1R43DK148203-01)

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NIH grant 1R43DK148203-01: Production in maize of low-cost heat stable forms of GLP-1 and GIP receptor agonists for treatment of diabetes and obesity
Institute: {'code': 'DK', 'abbreviation': 'NIDDK', 'name': 'National Institute of Diabetes and Digestive and Kidney Diseases', 'admin_org_id': '12500020', 'admin_funding_url': ''}. PI: John A. Howard. Award: $288221.
Start: 2026-09-30T00:00:00.
Glucagon-like peptide (GLP-1) receptor agonists have been in widespread use as a treatment for type 2
diabetes since 2005 and obesity since 2014. More recently, a peptide with a similar function, exendin, was
identified. These compounds, known as incretin mimetics, are found in a wide variety of tissues and influence
glucose metabolism, insulin and glucagon secretion, gastric emptying, and appetite. By some estimates up to
40% of the world’s population are living with obesity and the market is estimated to be up to $100 billion by 2030.
There is also extensive evidence that GLP-1 agonists have beneficial effects on numerous other conditions such
as cardiovascular health, arthritis, substance abuse, pain management, and prevention of neurodegenerative
diseases. These agonists are inherently prone to proteolysis, but extensive research has led to multiple
approaches to improve stability. However, there are still significant limitations to the widespread use of GLP-1
agonists. Treatment can cost $300 to $2000 per month, which is prohibitive for much of the world’s population
and there have been many reported shortages.
 We have developed a system in transgenic maize grain for the low-cost production of recombinant proteins
resulting in commercialization of the first of these products. This approach can greatly reduce the production
cost of the product while providing a system to rapidly scale-up production for a fraction of the upfront cost
associated with facilities for cell culture systems. We now plan to use this for GLP-1 agonists resulting in an
extremely low cost of production.
 In addition, maize grain can bioencapsulate recombinant proteins providing protection from proteases in the
gut. We have demonstrated that this extra level of protection can enable the oral delivery of proteins that
otherwise must be parenterally administered. We now plan to combine the use of 1) modified versions of GLP-
1 that have been shown to provide higher stability, 2) the bioencapsulation of proteins in maize to provide
protection in the digestive system and 3) the high levels of recombinant protein accumulation in maize to enable
oral delivery of small palatable tablets for administration. The extremely low cost of protein production in maize
(< $0.01/dose for the active ingredient), the stability of the protein in grain and digestive tract make this approach
likely to succeed and overcome previous barriers.
 The overarching objective of this proposal is to validate the use the maize platform to develop a low-
cost, heat-stable orally delivered form of GLP-1 and GIP receptor agonists. This can lead to further
optimization and the engagement of pharmaceutical partners to enable a much lower cost of treatments that can
be accessible in resource-limited areas.

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