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CHO Cell Engineering Service

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Overview Core Service Offerings Technology Platform and Advantages Application Areas Project Workflow Case Studies Frequently Asked Questions (FAQs) Contact Us

Overview

Chinese Hamster Ovary (CHO) cells are one of the most widely used host cells in the biopharmaceutical industry, particularly for the production of recombinant proteins, monoclonal antibodies, and vaccines. Due to their excellent growth characteristics and ability to produce complex proteins, CHO cells have become the gold standard for producing high-quality biological products. Our company offers advanced CHO cell engineering services designed to help our clients optimize production processes and accelerate the development of their biopharmaceuticals.

Schematic depiction of the effect of cell engineering on improved culture characteristics.(JY Kim, et al.,2012)

CHO Cell Engineering refers to the modification of China Hamster Ovary (CHO) cells through gene editing, cell line development and systems biology to improve their production efficiency and product quality in biopharmaceuticals. CHO cells are widely used in the industrial production of recombinant proteins because of their ability to efficiently express complex glycoproteins and good safety.

CHO cell engineering includes many aspects:

  1. Gene editing: Use gene editing technologies such as CRISPR-Cas9 to accurately modify the genome of CHO cells to enhance their growth rate, improve product quality, or enhance antiviral capabilities. For example, by knocking out or knocking in specific genes, the metabolic pathways and secretion mechanisms of CHO cells can be optimized.
  2. Cell line development: Establish efficient CHO cell lines through high-throughput screening and cloning techniques. These cell lines can stably express the target protein and have high yields and good biological activities. For example, the CHO-K1 cell line is currently one of the most widely used host cell lines in the biopharmaceutical industry.

Core Service Offerings

As a CRO service outsourcing company, providing CHO cell engineering services mainly include the following aspects:

  1. Upstream sequence optimization and vector construction: First, the target gene needs to be sequence optimized to improve its expression efficiency in CHO cells. Then, the optimized gene was introduced into CHO cells through vector construction technology.
  2. Cell strain construction: After introducing the optimized gene into CHO cells, a cell strain with the required characteristics is obtained through screening and cloning techniques. This step is the core of the entire project and directly affects the effect of subsequent production.
  3. Cell strain optimization and quality control testing: After obtaining a preliminary cell strain, it needs to be further optimized, including improving cell growth rate, extending cell life, and enhancing anti-apoptosis ability. At the same time, strict quality control testing is also needed to ensure the quality and stability of the cell line.
  4. Genome editing: Use high-throughput genomic data and computational models to systematically characterize CHO cells, and accurately modify target genes through genome editing technologies (such as CRISPR-Cas9, ZFN, etc.), thereby achieving regulation of cell functions.
  5. Optimization of glycosylation modifications: Proteins expressed by CHO cells usually need to be glycosylated to improve their clinical application. Through genetic engineering, the expression of glycosylation-related genes can be optimized, thereby improving the glycosylation pattern of antibodies and other biological products.
  6. Molecular tool applications: Using molecular tools such as miRNA overexpression or inhibition, the entire cell pathway can be engineered, thereby enhancing the performance of CHO cells in terms of production efficiency, growth speed, anti-apoptosis ability, metabolism, etc.
  7. Multi-omic data analysis: Combining multi-omic data sets (such as transcriptome, proteome, metabolome, etc.) can provide a more comprehensive understanding of the biological characteristics of CHO cells and guide subsequent engineering modifications.
  8. Customized services: Provide personalized CHO cell engineering solutions based on customers 'specific needs, including gene editing, cell strain development, optimization and quality control.

Through the above services, the application effect of CHO cells in the field of biopharmaceutical can be effectively improved, and all aspects from research and development to industrial production can be strongly supported.

Technology Platform and Advantages

Our CHO cell engineering services are built on cutting-edge technology platforms that ensure precise and efficient cell line modifications. Key advantages of our platform include:

  • Gene editing technology platform: Using CRISPR/Cas9-mediated targeted integration combined with homologous recombination cell engineering (RMCE), a cell line platform that expresses the same gene can be generated for the study of the relative stability of genomic engineering CHO cell lines.
  • High-throughput genome editing and computational model platform: Systematically characterize CHO cells through high-throughput genomic datasets and computational models to identify reasonable cell engineering goals and verify them through emerging genome editing technologies.
  • Stable cell strain construction platform: Provides one-stop service from gene synthesis to stable cell strain delivery, quickly assisting the research and development of antibody drugs.
  • Multi-omics datasets and genetic engineering platform: Use multi-omics datasets and genome editing technology to systematically characterize CHO cells to achieve accurate cell engineering.
  • Viral resistance engineering platform: CHO cells are genetically engineered to be resistant to specific viruses such as MVM.

Application Areas

Our CHO cell engineering services are designed to support a wide range of applications within the pharmaceutical and biotechnology industries, including:

  • Monoclonal Antibodies: CHO cells are widely used for the production of monoclonal antibodies, which are essential in immunotherapies and cancer treatments.
  • Recombinant Proteins: CHO cells are ideal for producing therapeutic proteins used to treat rare diseases, metabolic disorders, and other conditions.
  • Vaccines: Our services support the rapid development and large-scale production of next-generation vaccines, ensuring scalability and compliance with regulatory requirements.
  • Gene Therapy and Cell Therapy: CHO cell engineering plays a vital role in producing viral vectors and therapeutic proteins for gene and cell therapy applications.

Project Workflow

We offer a customized, end-to-end project management process for every client, providing transparency and control at each stage:

CHO cell engineering service Project Workflow

  1. Project start-up and needs analysis:
    • Accept customer entrustment and clarify project needs and goals. This includes understanding the protein types, expression levels, glycosylation characteristics, etc. that customers want to optimize.
  2. Cell strain selection and transformation:
    • Select a suitable CHO cell line as the expression host. According to the characteristics of the target protein, select the CHO cell subline with the best expression ability.
    • Carry out genetic engineering and manipulate target genes through gene editing technologies (such as CRISPR-Cas9, ZFN, etc.) to increase expression, improve glycosylation characteristics or enhance the anti-apoptosis ability of cells.
  3. Cell bank establishment and expansion:
    • Establish a stable CHO cell bank to ensure the genetic stability of cell lines. Cell expansion was carried out using serum-free media to ensure cell quality and consistency.
    • Freeze and recover cells to ensure their activity and stability during long-term storage.
  4. Medium optimization:
    • According to the characteristics of the target protein, optimize the medium components, including animal-free ingredients, serum-free medium, etc., to improve expression efficiency and product quality.
  5. Expression system construction and verification:
    • The expression vector was constructed and transformed into CHO cells. Efficient expression of the target protein is achieved through transient transfection or stable transfection.
    • Validation of the expression system includes assessment of protein expression levels, glycosylation modifications, protein purity and activity.
  6. Process development and scale-up:
    • The best expression conditions were screened out under small-scale culture conditions, and then gradually scaled up to industrial production scale.
    • Key parameters during the scale-up process are optimized to ensure that high-quality recombinant proteins can be stably obtained during large-scale production.
  7. Quality control and stability assessment:
    • Carry out comprehensive quality control on the expression products, including protein purity, activity, glycosylation modification, etc.
    • Conduct long-term stability assessments to ensure product stability and safety during storage and transportation.
  8. Customer delivery and technical support:
    • After all production steps are completed, high-quality recombinant protein is delivered to customers and necessary technical support and follow-up services are provided.

Through the above processes, we can provide customers with a full range of CHO cell engineering services from cell strain transformation to large-scale production, helping customers efficiently and stably produce high-quality biopharmaceutical products.

Case Studies

As a CRO service outsourcing company, providing CHO cell engineering services, the following is a summary of several customer cases and their results:

A research institute has multi-genetically engineered CHO cells by knocking in and knocking out genes to improve their anti-apoptosis ability. For example, they chose the B lymphomas-2 (Bcl-2) gene as a knock-in gene to enhance the cells 'ability to resist apoptosis. This transformation strategy has significantly improved the stability and yield of CHO cells in drug production.

In a specific industrial production case, the CHO cell fed-batch process is used for the production of recombinant proteins. Inoculate the cells in CHO CDpro medium at 0.5×10^6 cells/mL. After the cells grew stable, they were transferred to fed-batch medium for cultivation. By continuously replenishing glucose and feed solution, the final yield can reach 3- 4 g/L. The application of this process has significantly improved the production efficiency and quality of protein.

In another case, gene overexpression was used to increase the production of therapeutic proteins. By regulating the expression of specific genes in CHO cells, the researchers optimized the cells 'metabolic and secretory capabilities, thereby increasing the production of target proteins. This method not only increases protein production, but also improves protein quality.

Frequently Asked Questions (FAQs)

Optimization of CHO cell culture medium:

Question: How to optimize the ingredients in CHO cell culture medium?

Answer: Response surface methodology can be used to optimize the content of glucose, glutamine, serum and sodium bicarbonate in the medium to improve the growth and reproduction ability of CHO cells.

Gene editing technology for CHO cell engineering:

Question: How to perform gene editing of CHO cells?

Answer: CHO cells can be systematically characterized using high-throughput genomic analysis and computational models, and precise gene editing can be performed through genome editing techniques such as CompoZr® Zinc Finger Nuclease (ZFN).

Challenges for CHO cell expression systems:

Question: Will CHO cells grow delayed in serum-free suspension culture?

Answer: Studies have shown that CHO engineered cells do not experience the common growth delay when they are transferred from serum-containing medium to serum-free medium.

Metabolic engineering of CHO cell engineering:

Question: How to improve the productivity of CHO cells through metabolic engineering?

Answer: The productivity of CHO cells can be improved through metabolic network design and feeding strategies.

Glycosylation modifications for CHO cell engineering:

Question: How to improve the level of glycosylation modification of recombinant proteins?

Answer: The level of sialylation of recombinant therapeutic proteins can be increased by engineering glycosyltransferase genes.

Gene expression efficiency of CHO cell engineering:

Question: How to improve the expression efficiency of foreign genes in CHO cells?

Answer: Overexpression or inhibition of miRNAs can be used to regulate the entire cellular pathway, thereby enhancing CHO cells 'growth, anti-apoptosis and metabolic capabilities.

Cost and time issues of CHO cell engineering:

Question: Is CHO cell engineering time and cost intensive?

Answer: Yes, identifying new cell line engineering targets to improve CHO cells is a time-and cost-intensive process.

Contact Us

If you are interested in our CHO cell engineering services or would like more information about customized solutions, please don't hesitate to contact us. We offer project consultations, design plans, and pricing quotes to help you achieve your biopharmaceutical development objectives.

Please note that all services are for research use only. Not intended for any clinical use.

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