NSiS has developed a proprietary fully human protein platform that combines an engineered adenoviral vector with iPSC-derived human cells. By integrating human O- and N-glycosylation, native protein folding and complex assembly, endotoxin-free production, and high-efficiency expression within a single platform, NSiS enables the creation of complex proteins with structures and functions that more closely reflect those found naturally in the human body—proteins that have been difficult to produce using conventional systems. The platform’s core technologies are protected by granted and pending patents.
A Proprietary Platform Combining a Common Vector System with Human Cells
The key feature of the NSiS platform is the ability to select the most appropriate human host cell for each target protein while using a common Ad5/F35 adenoviral vector system. By leveraging the native protein synthesis and modification machinery of human cells, the platform enables rapid and reproducible production of complex human proteins.
ONE VECTOR SYSTEM
Ad5/F35 VECTOR
Common expression vector
SELECTABLE HUMAN HOST
HUMAN HOST CELLS
iPSC-derived; selected for the target protein
TARGET PROTEIN
FULLY HUMAN PROTEINS
Native-like folding & human PTMs
Tissue-Specific Host Cells Selected for Each Target Protein
NSiS can differentiate iPSCs into cell lineages derived from the ectoderm, mesoderm, and endoderm, allowing the selection of host cells best suited to each target protein. By leveraging the distinct glycosylation patterns, lipid environments, secretion mechanisms, and other characteristics of cells derived from tissues such as the nervous, vascular and immune, hepatic, and respiratory systems, the platform aims to reproduce protein structures and functions that more closely reflect their native environment in the human body.
For pathogen antigens in particular, selecting host cells corresponding to the tissues targeted by infection may enable more faithful reproduction of tissue-specific glycosylation patterns and structures found in the native pathogen. In addition, the platform can simultaneously express multiple proteins and control their relative expression levels, enabling the production of complex multi-chain proteins, including bispecific and multispecific antibodies.
ECTODERM
Neural progenitors
Ganglioside-rich membranes;
neuronal glycosyltransferases
Neurotropic: Nipah, rabies
MESODERM
Endothelial, cardiac,
haematopoietic
Endothelial and immune-cell
glycan and lipid environment
Lympho- and endothelio-tropic:
HIV, dengue
ENDODERM
Hepatocyte-like,
lung epithelial
Hepatic secretory machinery;
airway glycosylation
Respiratory, hepatotropic:
SARS-CoV-2, influenza
Expanding Beyond Conventional Expression Systems
Compared with conventional expression systems such as E. coli, CHO cells, and HEK293 cells, the NSiS platform leverages native human chaperones for protein folding and ER/Golgi-mediated glycosylation and sialylation. A key differentiating feature is its ability to reproduce tissue-specific glycosylation patterns and proteoform structures that are difficult to achieve with conventional expression systems. Furthermore, the use of iPSC-derived human cells provides a platform with the potential for future translation to GMP manufacturing.
| Capability | E. coli | CHO | HEK293 | NSiS tissue-derived |
NSiS iPSC-derived |
|---|---|---|---|---|---|
| Synthesis and protective modification | ○ | ○ | ○ | ○ | ○ |
| Human folding via native chaperones | × | △ | ○ | ○ | ○ |
| ER/Golgi glycosylation and sialylation | × | △ | ○ | ○ | ○ |
| Tissue-type glycan / proteoform structure | × | × | × | ○ | ○ |
| Transferability to GMP | ○ | ○ | △ | △ | ○ |
△ = Partially achievable or achievable with additional engineering or process development.
Rapid and Efficient Bioprocess
The NSiS platform substantially simplifies time-consuming steps such as cloning, cell line selection, and Master Cell Bank establishment. This enables protein production and purification in approximately two weeks from the start of cell culture, with the entire process, including adenovirus preparation, completed in approximately three months. The platform achieves up to approximately 50-fold higher productivity compared with conventional production systems.