Nanobody Discovery for Membrane Protein Targets

Low expression levels, structural instability after purification, poor solubility, and difficulty maintaining native conformations often limit the effectiveness of conventional discovery approaches. These challenges are especially pronounced for multi-pass transmembrane proteins and conformationally sensitive targets.

To improve discovery success against difficult membrane targets, our platform integrates native-conformation immunization strategies, membrane mimetic technologies, cell-based screening, and multiple display platforms to enable efficient identification of high-quality membrane protein binders.

Advantages of Our Membrane Protein Discovery

Native-Conformation Immunization Strategies

We support multiple antigen presentation approaches to preserve membrane protein structure during immunization, including:

Cell-based immunization

Virus-like particles (VLPs)

LNP-mRNA immunization

Viral vector-based expression

Membrane mimetic systems

These strategies help maintain physiologically relevant conformations for difficult membrane targets.

Cell-Based Screening

Phage display screening can be performed directly against target-expressing cells to enrich binders recognizing native membrane protein conformations.

Quantitative Yeast Display Screening

FACS-based yeast display screening supports affinity- and specificity-driven enrichment under tightly controlled selection conditions.

Flexible Discovery Routes

Immunization-Based Discovery

Recommended for:

Therapeutic discovery programs

Difficult membrane protein targets

High-affinity binder generation

Workflow:
Camelid immunization → Immune library construction → Screening & Monoclonal selection → Candidate validation

Premade Library Screening

Recommended for:

Rapid target validation

Early-stage exploratory studies

Fast binder identification

Workflow:
Premade library screening → Screening & Monoclonal selection → Candidate validation

Challenging Membrane Protein Targets We Support

GPCRs

Ion channels

Transporters

Receptor tyrosine kinases

Viral envelope proteins

Cell-surface receptors

Deliverables

Clients will receive:

Membrane protein-binding nanobody sequences

Candidate binder analysis report

Expression-ready constructs (optional)

Binding validation data (optional)

Comprehensive project report

Optional downstream services:

Nanobody humanization

Affinity maturation

Typical Project Timeline

Option 1 — Immunization-Based Discovery

Stage	Deliverables	Timeline
Immunization	Serum titer report	8 weeks
Library construction	Immune phage or yeast display library	3–4 weeks
Library screening	Enriched binder sequences and screening report	4-6 weeks
Optional candidate production	Purified VHH and expression-ready constructs	2–3 weeks
Optional validation	Binding and functional assay data	2–4 weeks

Typical total timeline:

Approximately 15-18 weeks depending on project complexity and screening strategy.

Option 2 — Premade Library Screening

Stage	Deliverables	Timeline
Library screening	Enriched CAR-oriented binder sequences	4-6 weeks
Optional candidate production	Purified VHH or expression-ready constructs	2–3 weeks
Optional validation	Binding and functional assay data	2–4 weeks

Typical total timeline:

Approximately 4–13 weeks depending on validation requirements.

Advantages of Our Membrane Protein Discovery Platform

Multiple membrane protein immunization strategies

Native-conformation screening approaches

Strong expertise in difficult targets

Advanced phage and yeast display technologies

Cell-based validation workflows

Flexible downstream engineering support