Monoclonal antibody therapeutics are traditionally administered through intravenous or subcutaneous routes, while opportunities exist for novel single domain antibodies (sdAbS) to be delivered through other ways, such as oral and inhaled administration. Creative Biolabs has over decades of experience in the discovery and development of novel sdAbs, which is a highly acclaimed service provider. We specialize in offering customized sdAb discovery solutions that can assist projects for oral immunotherapy and inhalation therapy applications.

Background

SdAb Oral Immunotherapy

The antibody application in oral immunotherapy is usually complicated as the antibody effectiveness can be limited by partial proteolytic degradation within the gastrointestinal (GI) tract. Some studies have shown that sdAb can retain functional activity in the gastrointestinal tract, which opens an alternative route of therapeutic sdAbs for potential applications such as the prevention and/or treatment of digested bacterial pathogens.

Due to the high stability, sdAbs can be rationally screened to retain folding and binding capacities at high concentrations of chaotropic agents such as acidic environments or proteases in the stomach. A series of promising results were reported that oral sdAbs can be an effective substitution for conventional administration routes in addressing inflammatory bowel disease. Another interesting example is using natural gut commensal bacteria (e.g., Lactococcus lactis) for local production of sdAbs to prevent sdAb proteolysis in the stomach environment. Daily oral administration of sdAb-secreting L. lactis results in local delivery of therapeutic sdAbs and significantly reduced inflammation.

Fig. 1 SdAb inhalation therapy for SARS-CoV-2.¹

SdAb Inhalation Therapy

Recently, inhalation has been recognized as a new potential route for the treatment of pulmonary diseases, which can be in place of regular systemic administration. This approach takes advantage of providing faster and more robust antiviral activity by direct administration to the respiratory tract. Based on the small size, simple and robust structure, high solubility, physical stability, and stress resistance of sdAbs, sdAbs have been shown promising prophylactic and therapeutic molecules, especially through inhalation system by nebulization. Inhaled delivery of sdAbs may offer many advantages for treating lung diseases, including delivery directly to the site of action, smaller doses to be administered, lower systemic exposure, and fewer potential side effects of the treatment.

Typical Workflow for High-Stability SdAb Discovery at Creative Biolabs

Predictable Outcomes from Our Custom SdAb Discovery Services

• Customized SdAb Library
• Identified Target-Specific SdAb In Silico Sequences
• Humanized SdAb with Enhanced Stability
• Purified SdAb Test Batch

With our deep understanding of oral immunotherapy and inhalation therapy applications, Creative Biolabs can also conduct sdAb stability evaluation and sdAb stability improvement as separate services to satisfy your specific requirements. If you are interested in learning more about our services and how Creative Biolabs can contribute to your projects, please do not hesitate to contact us.

Reference

1. Gai, Junwei, et al. "A potent neutralizing nanobody against SARS‐CoV‐2 with inhaled delivery potential." MedComm 2.1 (2021): 101-113. Distributed under Open Access license CC BY 4.0, without modification.

We are offering highly customized CRO services to assist your Single Domain Antibody (sdAb) related projects. Please Contact Us for more details.