Shenyan Bio: Balancing Quality Enhancement and Cost Reduction in CGT

As is well known, cancer is one of the leading causes of human death, and the emergence of Cell and Gene Therapy (CGT) holds promise for a complete cure of cancer.

However, CGT therapies also have obvious pain points: the prohibitively high treatment prices make them unaffordable for many patients and families. The steep pricing of gene and cell therapies primarily stems from the production costs of the products themselves. How to reduce costs while ensuring or even enhancing therapeutic efficacy will be key to the large-scale adoption of CGT drugs.

The primary costs of CGT products can be categorized into five major segments: viral vectors, equipment and consumables, labor and operations, quality control, and facility and equipment. For each company, the main cost components of CGT products vary and constitute core trade secrets.

Among these, one of the major bottlenecks in the development of CGT drugs is viral vector manufacturing and its large-scale GMP production. The high technical difficulty, complex processes, capacity shortages, and lengthy preparation cycles have constrained the overall development of the industry.

Scaling up viral vector production (to improve titer and yield) not only reduces the cost of cell and gene therapy (CGT) but also accelerates drug commercialization, making it a key focus for innovative pharmaceutical companies and contract development and manufacturing organizations (CDMOs).

Optimization of viral vector development and production will significantly reduce CGT-related costs, addressing key industry pain points.In May of this year, the Center for Drug Evaluation (CDE) also released the Technical Guidelines for Pharmaceutical Research and Evaluation of In Vitro Gene Modification Systems (Trial) (hereinafter referred to as the “Guidelines”), providing some answers regarding the construction of viral vectors.

The guidelines state: “There are multiple processes for preparing viral vectors, including preparation via transient transfection of packaging cell substrates with plasmid DNA,Prepared via a Stable Production Cell Line, or by infecting the cell substrate with a viral seed.” What are the respective advantages and disadvantages of the three manufacturing technologies proposed by the CDE? VCBeat promptly contacted Shenzhen Shenyan Biological Technology Co. LTD, a core domestic supplier in the CGT sector.

Ma Mo, CEO of Shenzhen Shenyan Biological Technology Co. LTD, told VCBeat that the most commonly used method for viral vector production is currently plasmid-based transient transfection. This is a laboratory technique whose greatest advantage is speed. Compared with the months required to screen and construct stable cell lines, plasmid-based vector production eliminates this step.

However, plasmid-based viral packaging is a stochastic process; consequently, during industrialization, the quality and batch-to-batch variability of viral vectors produced via plasmid transfection are often difficult to control, posing significant technical challenges for large-scale manufacturing.

The prerequisite for preparing viral vectors by infecting cell substrates with viral seeds is that the virus must be replication-competent. However, lentiviruses, which are most commonly used in cell therapy, are replication-incompetent; therefore, the most prevalent production method for lentiviruses remains plasmid-based transient transfection of cells.

Ma Mo explained, “The advantages of producing viral vectors using stable producer cell lines are obvious. The traditional transient transfection process involves introducing several plasmids into a large population of cells, making it impossible to control the number and ratio of plasmids taken up by each individual cell, which results in poor consistency in viral vector packaging. In contrast, stable producer cell lines eliminate this variability, thereby increasing the total yield per batch.”

It is evident that in large-scale production, bypassing the highly inefficient process of transient transfection would have a significant impact on viral vector manufacturing.

By establishing stable production cell lines that inherently contain the genes required for viral vector production from the outset, viral vectors can be produced directly upon scaling up the cells to the desired quantity, without the need for transfection. In addition to simplifying the manufacturing process, this approach significantly reduces costs. By engineering the production cell lines to integrate the relevant genes at the initial stage, these genes are amplified in tandem with cell expansion to meet production demands, thereby eliminating the need for transient plasmid transfection and reducing plasmid requirements.

“It not only reduced costs but also improved quality. It is extremely difficult to simultaneously satisfy these two contradictory dimensions.”

For two decades, academia and industry struggled to overcome the technical challenges associated with producing lentiviral vectors using stable cell lines. Yet Shenzhen Shenyan Biological Technology Co., LTD achieved this breakthrough in just a few years. This success is attributable to the accumulation of biotechnological advancements in recent years, which has enabled latecomers to stand on the shoulders of giants and achieve greater breakthroughs, as well as to Shenzhen Shenyan Biological Technology Co., LTD’s relentless pursuit and meticulous refinement of technology.

“First, the packaging of viral vectors involves the coordinated expression of multiple genes, which requires multi-gene insertion technology. Shenzhen Shenyan Biological Technology Co., LTD has already established a patent portfolio in this area. Second, achieving both high titer and high expression levels of lentiviruses necessitates the use of molecular switch technology to regulate gene expression. Implementing molecular switches in cell therapy is challenging; current technologies can only achieve a unidirectional state—either permanently ‘on’ or permanently ‘off.’ In contrast, Shenzhen Shenyan Biological Technology Co., LTD has successfully developed a system that can be reliably switched both on and off,” Ma Mo told VCBeat.

Shenzhen Shenyan Biological Technology Co. LTD has established a comprehensive presence in the research and development of CGT equipment and consumables, as well as in providing CGT CDMO/CRO services.To date, Shenzhen Shenyan Biological Technology Co., LTD has been in operation for eight years. While continuously refining its high-value-added products, the company remains committed to addressing fundamental industry challenges. Currently, Shenyan Biology has not only achieved commercialization of domestically produced automated cell preparation equipment in the device sector but has also leveraged years of accumulation to achieve breakthroughs and further refine viral vector production technologies.

Based on technological breakthroughs in viral vector processes and large-scale GMP manufacturing, Shenzhen Shenyan Biological Technology Co. LTD has developed a mature solution system—EuLV^®️System.

EuLV^®It is a lentiviral vector production system based on stable cell lines., using inducible stable producer cell lines to produce lentiviral vectors (EuLV) through high-cell-density suspension culture in chemically defined media.^®The lentiviral vector production system enables stable integration of the required VSV-G, gag/pol, rev, and gene of interest (GOI) into the genome of 293T cells without the need for plasmid transfection. Lentiviral vectors are then produced through drug-induced expression.

Use EuLV^®The system not only enhances the production efficiency of lentiviral vectors but also improves their quality, stability, and batch-to-batch consistency, while offering a manufacturing process that is easily scalable. Furthermore, by eliminating the use of plasmids in production, the need for dedicated GMP facilities and equipment for plasmid manufacturing is removed, thereby reducing associated labor and operational costs. This ultimately simplifies the lentiviral vector production workflow and shortens the related quality control processes. With this system, the specific activity of the virus can reach 1/10, the number of production steps is reduced by more than 50%, production efficiency is increased 100-fold, and costs are lowered by over 80%.

EuLV^®This technology breaks through current viral vector production methods, achieving global leadership and innovation in viral vector manufacturing for the gene and cell therapy industry. Key features include a plasmid-free process, induced virus production, and high consistency of lentiviral vectors.

Shenyan Biologics Offers EuLV^®Shenyan Bio’s comprehensive CRO services enable clients to receive the corresponding monoclonal cell lines within 4–6 months by simply providing the gene sequence or plasmid. Shenyan Bio also offers additional optional services, including GOI optimization, clone identification and stability studies, as well as upstream and downstream process development.

In addition, Shenzhen Shenyan Biological Technology Co. LTD has launched CellSep for the entire cell preparation process.^®PRO (hereinafter referred to as “CSP”) and CellSep^®MAX (hereinafter referred to as “CSM”) two fully enclosed automated cell processing systems.

CSP enables a series of standard and customized cell manufacturing processes, including PBMC isolation, magnetic bead incubation and washing, lentiviral centrifugal transduction, cell suspension concentration and washing, and aliquoting of cell products into bags. Furthermore, CSP can perform various other procedures such as cell thawing, umbilical cord blood separation, bone marrow separation, platelet depletion, and component blood separation. This system is suitable for the standardized production of a wide range of cell therapy products, including CAR-T, TCR-T, NK, TIL, and stem cells. By leveraging these manufacturing processes, CSP achieves automated production that ensures high product consistency, reduces GMP facility construction and operational costs, improves GMP utilization efficiency, and minimizes the need for manual operators during production, thereby effectively lowering the overall production costs of cell preparation.

For applications requiring larger culture volumes or higher cell counts, Shenzhen Shenyan Biological Technology Co., LTD has launched the CSM, a fully closed, automated continuous-flow cell processing system, this year. Leveraging the principle of continuous-flow centrifugation, the CSM automatically and rapidly concentrates and washes large-volume cell culture broths within a closed system, followed by final product aliquoting. The CSM is suitable for the research, development, and production of cell therapy products, as well as various cell therapy manufacturing processes including CAR-T, U-CART, CIK, TIL, CAR-NK, NK, and iPSC therapies. It promotes the evolution of cell therapy production workflows toward lower costs and higher quality, thereby helping industry clients reduce expenses and enhance efficiency.

In addition to this combination approach, Shenzhen Shenyan Biological Technology Co. LTD also has a set of“Cross-approach technique.”

The two founding members of Shenzhen Shenyan Biological Technology Co. LTD came from interdisciplinary backgrounds, one specializing in automation and the other in biotechnology. As a research-driven, multidisciplinary team, Shenzhen Shenyan Biological leverages the convergence and technological innovation across computer science, electronic engineering, nanomaterials, chemical engineering, and life sciences to develop a series of core technologies and processes for cell and gene therapy (CGT).

Ma Mo believes that “the ‘languages’ used by professionals from different disciplines are not the same, and there are in fact many barriers to communication between them.However, problems themselves are not confined to any single discipline; they exist independently in the world. When addressing these challenges, we should not rely solely on a single disciplinary perspective but rather adopt a multidimensional approach. Through repeated efforts to solve problems using interdisciplinary methods, Shenzhen Shenyan Biological Technology has fostered a strong sense of teamwork and mutual understanding within its team.

“Someone has to tackle the tough nuts,” Ma Mo said, looking back on the past.

After eight years of dedicated development, Shenyan Bio’s CSP system has been adopted by dozens of cell therapy companies in China, supporting IND filings, Phase I and II clinical trials, and product development for cellular drugs such as CAR-T, TCR-T, CAR-NK, TIL, and stem cell therapies.

In the field of viral vectors, Shenzhen Shenyan Biological Technology Co., LTD has also achieved commercialization this year, with domestic companies beginning to adopt this system for drug research and development as well as production. Meanwhile, the company has established a presence in regions such as the Americas and Europe by licensing subsequent overseas sales rights for its equipment, thereby expanding the accessibility of viral vector systems to enhance cost-efficiency in cell and gene therapy (CGT).

Shenzhen Shenyan Biological Technology Co. LTD has been able to achieve these phased results rapidly due to its robust technology, rapid response capabilities, and customized services. Furthermore, under the influence of macro-environmental factors such as international trade dynamics and the COVID-19 pandemic, domestic companies have placed greater emphasis on supply chain stability and cost efficiency, prompting local enterprises to actively adopt domestically produced equipment. Additionally, the rapid development of upstream suppliers in the cell and gene therapy (CGT) sector has been driven by the growing recognition among pharmaceutical companies that the feasibility of large-scale drug production is fundamentally a matter of process engineering.

“In terms of technology and product refinement, Shenzhen Shenyan Biological Technology Co. LTD has observed from the perspectives of both enterprise and market that only practicality-driven innovation ensures sustainable development. Therefore, Shenzhen Shenyan Biological Technology Co. LTD is committed to addressing some of the currently unresolved pain points in the field, which is also a key reason for our rapid recognition.”

Looking back on the eight years of entrepreneurship, Ma Mo has many reflections. In 2014, people were still in the stage of understanding and observing the CGT industry, and knew even less about the more "niche" upstream sector.“Yet, someone must tackle the hard nuts to crack, and someone must do the difficult but right things. We are fortunate to leverage our knowledge and insights to contribute to the industry and the world. While it is described as a contribution, it is also, in essence, a realization of our self-worth.”

For the entire industry, whether companies already have CGT products on the market or are in the R&D stage, the common goal is to reduce costs to an accessible range, facilitating the widespread adoption of CGT technologies and products. We look forward to more enterprises like Shenzhen Shenyan Biological Technology Co. LTD becoming core suppliers in the upstream field of CGT, helping CGT products achieve cost reduction and efficiency improvement at an early date.