Comparative omics profiling reveals differences in biomass, energy production, and vesicle transport between CHO and fast-growing CHL-YN cells – Nature

Report on a Novel Cell Line for Sustainable Biopharmaceutical Production

Introduction and Alignment with Sustainable Development Goals (SDGs)

This report details a comparative analysis of a novel Chinese hamster lung (CHL)-YN cell line against conventional Chinese hamster ovary (CHO) cells, the industry standard for producing therapeutic antibodies. The development and characterization of the CHL-YN cell line represent a significant innovation in biomanufacturing, with direct implications for several United Nations Sustainable Development Goals (SDGs).

• SDG 3: Good Health and Well-being: By accelerating the production of therapeutic antibodies, this innovation can improve access to essential medicines.
• SDG 9: Industry, Innovation, and Infrastructure: The research introduces a technological advancement that enhances the efficiency and sustainability of the biopharmaceutical industry.
• SDG 12: Responsible Consumption and Production: The superior efficiency of the CHL-YN cell line promotes more sustainable manufacturing patterns by potentially reducing resource consumption and production timelines.

Comparative Analysis of CHL-YN and CHO Cells

Core Performance Characteristics

The CHL-YN cell line exhibits several key characteristics that position it as a promising alternative to traditional CHO cells, contributing to more efficient and sustainable production models.

• Growth Rate: CHL-YN cells demonstrate a doubling time of 8.1 hours, which is more than twice as fast as the approximately 20-hour doubling time of CHO cells. This rapid growth directly supports SDG 9 by shortening production cycles.
• Metabolic Efficiency: The cells possess strong glutamine synthetase activity, allowing for cultivation in glutamine-free media. This simplifies the manufacturing process and reduces reliance on unstable supplements, aligning with the principles of SDG 12.
• Productivity and Quality: CHL-YN cells have been shown to produce comparable or greater amounts of immunoglobulin G1 (IgG1) in a shorter period than CHO cells, while maintaining a similar and human-compatible N-glycosylation profile, which is critical for therapeutic efficacy and safety under SDG 3.

Omics Profiling: Transcriptomic and Proteomic Insights

A comprehensive omics analysis was conducted to understand the underlying biological differences between CHL-YN cells, CHO cells, and the original Chinese hamster lung tissue. This analysis provides a scientific basis for the observed performance advantages and informs future engineering efforts in line with SDG 9.

1. CHL-YN Cell Profile:
   • Omics data revealed that CHL-YN cells have highly activated processes related to biomass and energy production.
   • Key upregulated pathways include translation, amino acid biosynthesis, and the TCA cycle, which collectively support rapid cell proliferation and resource efficiency.
   • Proteomic analysis confirmed heightened activity in cell cycle processes, such as DNA replication and mismatch repair, explaining the cell line’s rapid growth and potential for genomic stability.
2. CHO Cell Profile:
   • In contrast, CHO cells showed higher activation of post-translational and secretory pathways.
   • Processes such as vesicle transport (e.g., Golgi-related transport), protein processing in the endoplasmic reticulum, and glycan metabolism were more pronounced, reflecting their established role as efficient secretors of recombinant proteins.
3. Tissue of Origin Comparison:
   • The analysis determined that while some metabolic features of CHL-YN cells are derived from their lung tissue origin, the most significant traits for industrial application—notably the highly active translation and cell cycle processes—are unique characteristics of the established cell line.

Implications for Sustainable Development

Contribution to SDG 3: Good Health and Well-being

• The accelerated growth rate of CHL-YN cells has the potential to reduce the time required for screening high-producing clones and scaling up cell cultures by half.
• This dramatic reduction in development and manufacturing timelines can bring vital therapeutic antibodies to patients more quickly.
• Streamlined and more efficient production processes may lead to lower manufacturing costs, enhancing the global affordability and accessibility of biopharmaceuticals.

Advancements for SDG 9: Industry, Innovation, and Infrastructure

• The CHL-YN cell line is a significant technological innovation that diversifies and strengthens the infrastructure of the biopharmaceutical industry.
• It provides an alternative production host that can be selected to meet specific process objectives, such as rapid development for emerging health threats.
• The distinct biological characteristics identified in this study offer valuable targets for future cell engineering, aimed at further improving the growth and productivity of both CHL-YN and traditional CHO cells.

Enhancing SDG 12: Responsible Consumption and Production

• Faster production cycles directly contribute to more efficient use of industrial resources, including energy, water, and single-use consumables, per unit of therapeutic product.
• The intrinsic ability of CHL-YN cells to biosynthesize key amino acids (e.g., cysteine) and thrive without glutamine reduces the complexity and resource intensity of culture media, promoting more sustainable production patterns.
• By optimizing cellular processes for biomass and energy, the CHL-YN cell line provides a foundation for developing biomanufacturing platforms with a reduced environmental footprint.

Analysis of Sustainable Development Goals (SDGs) in the Article

1. Which SDGs are addressed or connected to the issues highlighted in the article?

1. SDG 3: Good Health and Well-being

   The article’s primary focus is on improving the production of “therapeutic antibodies,” which are critical medicines for treating a wide range of diseases, including cancers and autoimmune disorders. By developing a novel cell line (CHL-YN) that can “shorten the research, development, and manufacturing timelines in biopharmaceutical production,” the research directly contributes to making essential medicines more accessible and potentially more affordable, thereby promoting health and well-being.

2. SDG 9: Industry, Innovation, and Infrastructure

   This research is a clear example of industrial innovation. The development and characterization of the “novel host cell line” CHL-YN represents a significant technological advancement in the biopharmaceutical industry. The study uses advanced scientific methods like “comparative transcriptomics and proteomics” to understand cellular mechanisms, aiming to “upgrade the technological capabilities” of biomanufacturing. The goal to “streamline operations” and “expand options for selectable cell lines” directly supports building resilient infrastructure and fostering innovation within a key industrial sector.

3. SDG 8: Decent Work and Economic Growth

   The article addresses economic productivity by focusing on efficiency improvements in a high-value industry. The finding that “CHL-YN cells grow twice as fast as Chinese hamster ovary (CHO) cells” and have the potential to “reduce by half the time typically required” for clone screening and scale-up points to a significant increase in productivity. Such innovations contribute to achieving higher levels of economic productivity through technological upgrading, which is a cornerstone of sustainable economic growth.

2. What specific targets under those SDGs can be identified based on the article’s content?

1. Under SDG 3: Good Health and Well-being

   • Target 3.b: Support the research and development of vaccines and medicines for the communicable and non-communicable diseases… provide access to affordable essential medicines and vaccines…
     
     The article directly supports this target by focusing on research to improve the manufacturing of “therapeutic monoclonal antibodies.” Innovations that make production faster and more efficient, as described with CHL-YN cells, are a crucial step toward increasing the global supply and accessibility of these essential medicines.

2. Under SDG 9: Industry, Innovation, and Infrastructure

   • Target 9.5: Enhance scientific research, upgrade the technological capabilities of industrial sectors in all countries… encouraging innovation and substantially increasing the number of research and development workers…
     
     The entire study is an exercise in enhancing scientific research. By performing “omics profiling” and identifying “potential biomarkers and targets for cell engineering,” the research aims to upgrade the technological capabilities of the biopharmaceutical industry. The publication itself contributes to the body of scientific knowledge that drives innovation.
   • Target 9.b: Support domestic technology development, research and innovation in developing countries, including by ensuring a conducive policy environment for, inter alia, industrial diversification and value addition to commodities.
     
     The development of the CHL-YN cell line is a tangible outcome of technology development and research. Creating new, efficient host cell lines expands the technological toolkit available for biomanufacturing, supporting industrial diversification and adding value to the production of biopharmaceuticals.

3. Under SDG 8: Decent Work and Economic Growth

   • Target 8.2: Achieve higher levels of economic productivity through diversification, technological upgrading and innovation…
     
     The article’s central theme is enhancing productivity. The faster growth of CHL-YN cells (“doubling time of 8.1 h” compared to “approximately 20 h” for CHO cells) is a technological innovation aimed squarely at increasing the productivity of biopharmaceutical manufacturing, a high-value-added sector.

3. Are there any indicators mentioned or implied in the article that can be used to measure progress towards the identified targets?

While the article does not mention official SDG indicators, it contains specific data and outcomes that can serve as proxy indicators for measuring progress:

• Indicator: Reduction in Production Time / Increased Growth Rate.
  
  This is a direct measure of increased productivity and efficiency (relevant to Targets 8.2 and 9.5). The article provides quantifiable data: “CHL-YN cells grow twice as fast as Chinese hamster ovary (CHO) cells, with a doubling time of 8.1 h.” This metric can be used to track progress in shortening manufacturing timelines.
• Indicator: Increased Product Yield in a Shorter Timeframe.
  
  This measures the efficiency of medicine production (relevant to Target 3.b). The article states that “CHL-YN cells have been reported to produce a similar amount or more of immunoglobulin G1 (IgG1) to CHO-K1 cells in a shorter period.” This demonstrates an improvement in production capacity over time.
• Indicator: Development of New Technologies and Scientific Insights.
  
  This is relevant to Target 9.5. The article itself, as a scientific publication detailing the “omics profiling” of a “novel host cell line,” is an indicator of ongoing R&D. The identification of “potential biomarkers and targets for cell engineering” represents the creation of new knowledge to fuel further innovation.

4. Table of Findings

Source: nature.com