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Evaluation of recombinant bovine lactoferrin and N-linked glycan effects on infant gut health and immunity

Award Information
Agency: Department of Health and Human Services
Branch: National Institutes of Health
Contract: 1R41HD114267-01
Agency Tracking Number: R41HD114267
Amount: $311,323.00
Phase: Phase I
Program: STTR
Solicitation Topic Code: NICHD
Solicitation Number: PA22-178
Solicitation Year: 2022
Award Year: 2023
Award Start Date (Proposal Award Date): 2023-09-19
Award End Date (Contract End Date): 2024-08-31
Small Business Information
1100 MAIN ST STE 300
Woodland, CA 95695-3522
United States
DUNS: 118275260
HUBZone Owned: No
Woman Owned: No
Socially and Economically Disadvantaged: No
Principal Investigator
 (916) 743-4080
Business Contact
Phone: (916) 743-4080
Research Institution
OFFICE OF RESEARCH - SPONSORED PROGRAMS 1850 Research Park Drive, Suite 300
DAVIS, CA 95618-6153
United States

 Nonprofit College or University

Project Summary/Abstract
Most infants currently rely on infant formula (IF) to meet their nutritional needs. However, existing infant
formula is functionally inferior because it lacks breast milk bioactive proteins that are crucial to infant health
and development. Consequently, formula-fed infants have increased risk of morbidity and mortality. Current
technology limits the ability to add bioactive milk proteins to infant formula because manufacturing
processes are resource intensive, costly, and difficult to scale. Thus, scalable technology to improve
bioactive availability for fortification of infant formula is needed. Towards this goal, TurtleTree has
developed precision fermentation technology to produce recombinant bovine lactoferrin (rbLf), a critical
bioactive milk protein demonstrated to support gut health and immune function in infants. Not only will
TurtleTree’s technology allow for inclusion of lactoferrin in all infant formulas, but the use of precision
fermentation will also dissociate bioactive milk protein production from animal agriculture, as required for
cow’s milk-derived lactoferrin (cMDLf), and the associated environmental stressors. In this proposal, we
aim to answer two specific questions that will validate our ability to apply precision fermentation technology
for infant health and commercialize rbLf as an ingredient for addition to infant formula: 1) Does the unique
glycosolation profile of rbLf impact the protein’s immunomodulatory and gut function as compared to
cMDLf? 2) Does rbLf improve gut health in an infant preclinical mouse model? Preliminary data supporting
this proposal demonstrates the N-linked glycan profile is the only substantially unique structural element of
rbLf, characterized by dominance of high-mannose type glycans (~99%) compared to cMDLf (~45%). Thus,
we reason a proper evaluation of rbLf requires focused studies on physiological systems sensitive to glycan
alterations, notably immune interactions (Aim 1) and gut development (Aim 2). Comparative results
between differentially glycosylated lactoferrin treatment groups will distinguish glycan effects. In Aim 1, we
will assess the role of lactoferrin N-linked glycosylation on immunomodulation mediated by the mannose
receptor in order to understand glycan effect. In Aim 2, we will execute an intervention of orally-delivered
rbLf to improve dysregulated gut health in infant mouse pups. With the successful completion of both aims,
we expect to demonstrate rbLf promotes immune and gut interactions that maintain biological activity and
efficacy as compared to cMDLf. The scope of work is designed to support regulatory approval and expedite
TurtleTree’s path to market for the safe and effective application of advancing infant health.

* Information listed above is at the time of submission. *

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