Autoimmune & Inflammatory Diseases

Advancing the frontier of autoimmune and inflammatory disease research requires tools that enable precise manipulation of biological systems at the molecular level. Our proprietary GCEngine platform addresses this need by enabling the site-specific incorporation of non-canonical amino acids (ncAAs) into peptides, proteins, antibodies, and cytokines that are directly involved in autoimmune and inflammatory pathways. This unlocks chemical functionalities that are not accessible with standard amino acids and allows researchers and developers to design molecules with behavior tailored to specific immune contexts. Uniquely positioned to decipher complex mechanisms, engineer next-generation biologics, and develop specific diagnostic probes, this technology positions our team as a strong partner in translating groundbreaking science into targeted solutions.

Applications of ncAA Incorporation in Autoimmune & Inflammatory Diseases

The incorporation of ncAAs is revolutionizing the study and treatment of autoimmune and inflammatory diseases by enabling the design of engineered proteins with tailored functionalities. Key applications include the development of site-specifically modified biologics, such as antibody-drug conjugates (ADCs), which allow targeted delivery of potent anti-inflammatory agents to immune cells while minimizing off-target effects. Here, the payload can be immunomodulatory (rather than cytotoxic), such as tolerogenic agents, targeted cytokine modulators, or pathway-specific inhibitors.

Fig.1 GCE enables the generation of an IL-2 variant through site-specific FSY incorporation. (Zhang, B., et al., 2023)

Additionally, ncAAs enable the introduction of unique chemical handles, cross-linkers, or post-translational modifications into autoantigens, facilitating high-resolution studies of antigen-antibody interactions and the development of highly sensitive diagnostic assays. This technology also supports the engineering of immune cell receptors and signaling molecules with novel functions for use in advanced cell therapies.

Our Services

Leveraging a comprehensive and proprietary GCEngine platform, we offer end-to-end services tailored for autoimmune and inflammatory disease research applications, from the initial high-throughput identification of optimal orthogonal aaRS/tRNA pairs, rigorous in vitro validation of ncAA incorporation efficiency and fidelity within disease-associated proteins, to testing therapeutic efficacy and safety in relevant preclinical models, providing a seamless pathway from concept to functional validation.

Pharmaceutical R&D Solutions for Autoimmune & Inflammatory Disease

Precisely advancing therapeutic innovation for autoimmune & inflammatory diseases, our GCEngine platform empowers the development of novel, functionally enhanced biologics through site-specific incorporation of ncAAs. This capability is directly applied to several pivotal areas:

Immunomodulatory Peptide Therapy Development

Transform unstable peptide candidates that modulate key immune pathways (e.g., T cell, B cell, or innate signaling) into stabilized therapeutics with enhanced bioavailability. This service also supports the introduction of microenvironment-specific conditional activation mechanisms to minimize systemic immunosuppression, or the development of peptide-based probes for sensitive detection of immune activity in autoimmune or inflammatory settings.

Key deliverables

• Strategic design of ncAA-containing architectures incorporating stapling, cyclization, or conformational locking for proteolytic resistance.
• Precise incorporation of ncAAs to enable conditional activation within inflammatory microenvironments.
• Comprehensive generation and characterization of panels of ncAA-modified peptide variants.

ncAA Incorporated Protein Therapeutic Development

Specialized in developing non-antibody protein therapeutics, including receptor-ligand constructs, fusion proteins, and enzyme therapies for autoimmune and inflammatory diseases. By incorporating ncAAs at rationally selected sites guided by structure-function analysis, which can enhance target specificity and reduce off-target immune activation. Our service also includes site-specific conjugation via ncAA handles for half-life extension, targeted delivery, or probe attachment.

Key deliverables

• Structure-function guided identification of optimal ncAA incorporation sites.
• Generation of ncAA-engineered protein variant panels with defined modification sites.
• Execution of site-specific conjugation.
• In-depth characterization of activity, specificity, stability, and immunogenicity using relevant in vitro models.

ncAA Incorporated Antibody Therapeutic Development

Focused on creating next-generation antibody therapeutics with site-specific modifications, including ADCs or antibody-effector conjugates that deliver anti-inflammatory or tolerogenic payloads to specific immune cell subsets. ncAA incorporation enables homogeneous, site-specific conjugation of drug payloads, PEG chains for half-life extension, or functional groups to improve pharmacokinetics, reduce variability, and fine-tune Fc-mediated effector functions (e.g., ADCC, CDC, FcγR binding).

Key deliverables

• Design of ncAA incorporation sites on antibodies or antibody fragments compatible with your desired conjugation strategy.
• Production of engineered antibodies suitable for site-specific conjugation.
• Generation and characterization of homogeneous ADC-like constructs with controlled DARs.
• Evaluation of binding, effector function, and functional activity in immune cell-based assays.

ncAA Incorporated Cytokine Engineering

To achieve superior therapeutic specificity, we engineer cytokine variants designed to expand regulatory/tolerogenic cell populations (e.g., Tregs) while minimizing effector cell activation. This strategy allows for the introduction of conditionally activated mechanisms (e.g., tissue/cell-restricted signaling) or signaling bias via ncAA incorporation, effectively separating therapeutic anti-inflammatory effects from adverse pro-inflammatory responses.

Key deliverables

• Site-specific ncAA incorporation for covalent receptor binding, affinity modulation, or biased signaling.
• Introduction of ncAA-based conditional switches (e.g., photocontrol, protease activation, microenvironment sensitivity).
• Generation and characterization of panels of ncAA-engineered cytokine variants.

Contact Us

Providing a distinct competitive edge through deep expertise in both GCE technology and its application in immunology, our collaborative approach ensures the delivery of customized, robust solutions that accelerate discovery and development timelines. By enabling the precise engineering of biological molecules, we empower our partners to overcome hurdles in autoimmune and inflammatory disease R&D. For a detailed discussion on how our platform can advance your specific program, please contact us.

References

1. Zhang, Bo et al. "Proximity-enabled covalent binding of IL-2 to IL-2Rα selectively activates regulatory T cells and suppresses autoimmunity." Signal transduction and targeted therapy 8.1 (2023): 28.
2. Pham, Phuong Ngoc et al. "Regulation of IL-24/IL-20R2 complex formation using photocaged tyrosines and UV light." Frontiers in molecular biosciences 10 (2023): 1214235.