# A new platform for inexpensive and scalable recombinant protein and growth factor production to support cell culture applications in therapeutics.

> **NIH NIH R43** · OPERA BIOSCIENCE, INC. · 2024 · $275,765

## Abstract

Opera Bioscience proposes to develop a platform based on the type III secretion system of Salmonella enterica
typhimurium, which transports proteins from the cytoplasm to the extracellular space in a single step, to produce
cost effective growth factors and recombinant proteins for therapeutic use. Recombinant proteins underlie all
facets of biomedical research and therapeutic development. Advancements in genomics, bioinformatics, and
tools for genetic manipulation have led to an exponential growth in demand for recombinant proteins to study
disease phenotypes, develop therapeutic candidates, and support cell culture for live cellular therapies. Growth
factors are in demand for the latter application, especially because of the recent promise of therapies such as
CAR-T cells. Many growth factors are expensive to produce with current technologies, leading to increased
manufacturing costs for treatments. A novel protein expression system that lowers costs and simplifies the
production process would decrease the cost of therapeutic development and manufacturing and expand access
to these life-saving products. Bacterial expression systems are preferred for their low cost, high yield, and genetic
tractability, but traditional expression strategies require cell lysis and expensive downstream purification
processes to recover the product. Non-native proteins often accumulate in insoluble aggregates, which increases
cost and complexity by requiring extensive process optimization to recover a soluble and active product. Bacterial
protein secretion combines the advantages of traditional bacterial protein expression with the significant benefit
of recovering the product from the cell culture medium without cell lysis. This improvement creates high purity
proteins that significantly reduces downstream recovery costs and complexity. Secretion also improves product
yield by enabling continuous manufacturing technology, which is not currently used in bacterial expression
systems. Opera’s platform produces titers on the order of hundreds of milligrams per liter and generate soluble,
active enzymes, antibody fragments, and antimicrobial peptides. In this Phase I proposal, Opera outlines an
approach to adapt its platform for commercial use. In Aim 1, Opera describes a strategy to create an optimized,
safe production strain by removing unnecessary and pathogenic elements to increase safety and initial protein
purity and improve strain performance in suspension culture. In Aim 2, Opera Bioscience will unravel the T3SS
response to environmental stimuli by defining an optimal growth environment (dissolved oxygen and shear
stress, growth medium composition, and temperature) that maximizes secreted protein titer and yields operating
parameters Opera can use to scale the technology. The successful outcome of this proposal will be a
streamlined, optimized strain with a process environment that promotes secreted titers of growth factors that
match or exceed published values...

## Key facts

- **NIH application ID:** 10699041
- **Project number:** 1R43GM146560-01A1
- **Recipient organization:** OPERA BIOSCIENCE, INC.
- **Principal Investigator:** Julie Ming Liang
- **Activity code:** R43 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $275,765
- **Award type:** 1
- **Project period:** 2024-09-20 → 2025-09-19

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10699041

## Citation

> US National Institutes of Health, RePORTER application 10699041, A new platform for inexpensive and scalable recombinant protein and growth factor production to support cell culture applications in therapeutics. (1R43GM146560-01A1). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10699041. Licensed CC0.

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