# Engineering optimized N-glycosylation in the silkworm silkgland protein expression system

> **NIH NIH R01** · UNIVERSITY OF NOTRE DAME · 2021 · $497,951

## Abstract

PROJECT SUMMARY
 Many biomedically significant proteins, including antibodies, cytokines, anticoagulants, blood clotting
factors, and others are glycoproteins. Thus, there is a high demand for systems that can be used to produce
recombinant glycoproteins for basic biomedical research and direct clinical applications. Unfortunately, few
currently available recombinant protein production systems can produce higher eukaryotic glycoproteins with
authentic, relatively homogeneous carbohydrate side chains at relatively low cost. The long-term objective of
this proposal is to genetically engineer the silkworm, Bombyx mori, as a system that can fulfill these
requirements for recombinant glycoprotein production. Numerous studies have shown that the silkworm silk
gland, which has evolved for millions of years as a highly efficient silk protein production and secretion organ,
can be engineered to efficiently produce and secrete recombinant proteins. However, transgenic silkworms
have not yet been effectively used for recombinant glycoprotein production because the endogenous protein
glycosylation pathways of the silk gland cannot properly glycosylate foreign, higher eukaryotic glycoproteins.
 The proposed research seeks to develop the silkworm as a novel system for recombinant human
glycoprotein production by creating transgenic silkworms encoding a set of higher eukaryotic enzymes needed
to “humanize” the native silk gland protein N-glycosylation pathway and recombinant human N-glycoproteins of
interest. Each transgene will be placed under the control of the tissue-specific Ser1 promoter to target its
expression to the middle silk gland.
 To our knowledge, there is only one prior report of the effective genetic engineering of a protein
glycosylation pathway in any multicellular animal, including B. mori. We will build upon our initial success of
glycoengineering the protein N-glycosylation pathway of B. mori to significantly advance the use of the silk
gland as a bioreactor for recombinant glycoprotein production and secretion. This will have a net positive effect
on silk industries in both developed and underdeveloped countries worldwide, allowing value added products
important for human health to be produced in an economically feasible manner in addition to the basic silk
fiber, thereby significantly increasing the value of this important biomanufacturing platform.
 The Jarvis and Fraser laboratories have a demonstrated ability to perform this research as shown by their
publication records. In addition, they have been productively collaborating on related projects for the past 15
years, generating a significant amount of relevant preliminary data. The complementary skills available in these
two labs, their established working relationship, and the preliminary data obtained to date strongly suggest the
proposed research can be successfully completed.

## Key facts

- **NIH application ID:** 10136635
- **Project number:** 5R01GM130969-03
- **Recipient organization:** UNIVERSITY OF NOTRE DAME
- **Principal Investigator:** Malcolm J. FRASER
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $497,951
- **Award type:** 5
- **Project period:** 2019-08-01 → 2023-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10136635

## Citation

> US National Institutes of Health, RePORTER application 10136635, Engineering optimized N-glycosylation in the silkworm silkgland protein expression system (5R01GM130969-03). Retrieved via AI Analytics 2026-05-21 from https://api.ai-analytics.org/grant/nih/10136635. Licensed CC0.

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