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

> **NIH NIH R41** · TURTLETREE LABS INC. · 2023 · $311,323

## Abstract

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.

## Key facts

- **NIH application ID:** 10821138
- **Project number:** 1R41HD114267-01
- **Recipient organization:** TURTLETREE LABS INC.
- **Principal Investigator:** Vanessa Patricia Feher Castagna
- **Activity code:** R41 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2023
- **Award amount:** $311,323
- **Award type:** 1
- **Project period:** 2023-09-19 → 2025-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10821138

## Citation

> US National Institutes of Health, RePORTER application 10821138, Evaluation of recombinant bovine lactoferrin and N-linked glycan effects on infant gut health and immunity (1R41HD114267-01). Retrieved via AI Analytics 2026-06-23 from https://api.ai-analytics.org/grant/nih/10821138. Licensed CC0.

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