About Us

Nebulabio is a world-leading Contract Research Organization (CRO) specialized in next-generation antibody discovery. While we excel in in vitro display technologies, our Native Antibody Discovery Services represent the pinnacle of leveraging the human immune system's exquisite power. We partner with pharmaceutical and biotechnology companies to isolate and characterize naturally occurring, antigen-specific antibodies directly from human donors—whether convalescent patients, vaccinated individuals, or those with autoimmune conditions. Our platform combines cutting-edge single-cell technologies, high-throughput sequencing, and sophisticated bioinformatics to mine the immune repertoire with unprecedented precision and speed. By starting with nature's own optimized binders, we deliver fully-human, functionally relevant antibody leads with superior developability profiles, dramatically accelerating the path to clinical candidates.

☞Introduction to Native Antibodies

Native antibodies refer to immunoglobulin G (IgG) molecules that are naturally produced in vivo by an individual's B cells in response to antigen exposure. Unlike antibodies generated through synthetic library screening or animal immunization followed by humanization, native antibodies are inherently fully human and have undergone the body's own sophisticated selection and affinity maturation processes.

These antibodies offer several intrinsic advantages:

• Proven Biological Relevance: They are part of a successful physiological immune response, often associated with neutralization, clearance, or protective immunity.

• Optimal Developability: Having evolved in the human body, they typically exhibit excellent stability, solubility, and low immunogenicity risk.

• Diverse Functional Modalities: The native immune response generates antibodies with various functions—neutralizing, blocking, agonistic, or effector-engaging—providing a rich starting point for therapeutic development.

• Epitope Diversity: Convalescent or immunized donors produce antibodies against a broad range of epitopes on a target, including complex, discontinuous, and conformationally sensitive ones that are difficult to access via in vitro methods.

☞Principle of Our Native Antibody Discovery Technology

Our service is built on a foundational principle: the most powerful antibody discovery engine is the human immune system itself. We directly access the antigen-specific memory B cell repertoire from donor peripheral blood mononuclear cells (PBMCs).

The core technological pillars are:

• Antigen-Specific B Cell Isolation: We use state-of-the-art fluorescent-activated cell sorting (FACS) or magnetic-activated cell sorting (MACS) with labeled target antigens to physically isolate the rare B cells that produce antibodies against your target of interest.

• Single-Cell Analysis & Sequencing: Individual antigen-positive B cells are captured. We then perform single-cell RT-PCR to amplify the paired heavy- and light-chain variable region genes (VH and VL) from each cell. This preserves the natural, productive pairing as it existed in the human body.

• High-Throughput Sequencing & Bioinformatics: The amplified antibody genes are subjected to next-generation sequencing (NGS). Our proprietary bioinformatics pipeline analyzes the sequences, identifies clonal families, and reconstructs the antibody sequences for expression.

• Recombinant Expression & Screening: The paired VH/VL genes are cloned into mammalian expression vectors (e.g., for IgG1) and produced as full-length monoclonal antibodies. These are then screened in high-throughput assays for functional characteristics such as binding affinity, neutralization potency, or effector function.

This direct-from-B-cell approach ensures the recovery of antibodies with their natural, optimal chain pairing and glycosylation patterns, which are critical for function.

☞Native Antibody Discovery Service Process

Our end-to-end process is designed to efficiently convert donor immune cells into a panel of characterized, recombinant monoclonal antibodies.

☞Our Integrated Service Workflow

Our client-facing workflow ensures clarity, collaboration, and project success from initiation to delivery.

 Step 1: Project Consultation & Donor Strategy 

We discuss your target and therapeutic goals to define the optimal donor criteria and project scope.

Step 2: Donor Identification & Cell Procurement

We source or receive donor PBMC samples. A project kick-off report confirms sample details.

Step 3: B Cell Sorting & Single-Cell Processing

Our core discovery engine is activated. We provide a technical report confirming the frequency and sorting of antigen-specific B cells.

Step 4: NGS Sequencing & Bioinformatics Lead Selection

We sequence the repertoire and deliver a bioinformatics report detailing the discovered antibody repertoire, clonal families, and our recommendations for lead candidates to take forward.

Step 5: Lead Antibody Production & Validation

The selected antibody genes are expressed as full IgGs and put through the agreed validation assays. Regular data updates are provided.

Step 6: Final Delivery & Reporting

You receive the comprehensive final dataset, all antibody sequences, expression plasmids for top leads, purified antibody samples, and a detailed project summary with recommendations for further development.

 Our Service Process Flowchart: 

☞Advantages of Our Native Antibody Discovery Services

Choosing our platform provides a decisive strategic edge in therapeutic antibody development:

• Access to Fully-Human, Pre-Validated Leads: Recover antibodies that are naturally optimized for function in the human body, bypassing the need for humanization and significantly reducing immunogenicity risk.

• Superior Success Rate for Difficult Targets: For complex targets like viral antigens, cancer neoantigens, or self-antigens in autoimmunity, the native immune system has already solved the binding and specificity challenge. We simply "fish out" the solution.

• Direct Path to Functional Antibodies: Isolated antibodies are often intrinsically neutralizing or blocking, as they are sourced from a protective or pathogenic immune response, saving months of functional screening.

• Rich Intellectual Property (IP) Position: Discovering a naturally occurring antibody against a novel epitope can create a strong, defensible IP position.

• Complement to Display Technologies: This service is not a replacement but a powerful complement to phage/yeast display. It is the ideal first approach for targets with known human immunogenicity, while display technologies excel for non-immunogenic targets.

• Speed and Depth: Modern single-cell and NGS technologies allow us to interrogate millions of B cells and deliver tens to hundreds of unique, sequence-confirmed leads within 4-6 months.

• Expertise in Immune Repertoire Biology: Our team includes immunologists who provide deep insights into the donor response, clonal dynamics, and epitope spread, adding valuable biological context to the antibody leads.

Unlock the power of natural immunity for your most critical therapeutic programs. Contact our team to explore how our Native Antibody Discovery Services can deliver the high-quality, functional leads you need to accelerate toward the clinic.