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Gulliver Biomed

We provide high quality custom camelid single-domain antibodies (sdAbs, aka VHHs, nanobodies). Benefit from > 25 years know-how in nanobody discovery & applying them in diverse biological and clinical backgrounds. We also offer in-house developed nanobodies.

Immunoglobulins (IgGs) assume a profound role in research, diagnostics and therapeutics, but suffer from several drawbacks:

  • Very large proteins (150 kDa), 4 amino acid chains, complex structure.
  • Researchers rarely have their cDNA.
  • IgGs routinely cannot be used intracellularly (although the cytoplasm harbours thousands of proteins for which specific inhibitors are lacking). 
  • Coupling an antibody to a drug, lipid, quantum dot, gold nanoparticle,… is cumbersome and requires intricate chemistry.

These problems are not encountered with Nanobodies.

Heavy chain only antibodies (HcAbs) from camelids were discovered in Brussels, Belgium (figure below). The antigen-binding fragment of such a HcAb is called a nanobody, VHH, or single domain antibody. Belgium is a hub for nanobody research in academia and private enterprises alike.

  • Nanobodies are 10 times smaller than IgGs, consist of a single chain of amino acids, simple structure. High affinity binders (nM-pM in monovalent format).
  • Nanobody cDNA always obtained by default.
  • Nanobodies are stable in the cytoplasm of eukaryotic cells and can be transfected in cells, like any other cDNA by cloning in an expression vector.
  • Straightforward, site-specific and reproducible site specific nanobody derivatization.
  • Nanobodies are like a molecular stethoscope, they scan POI surface and identify important epitopes.

Conventional antibodies, heavy chain-only antibodies (HCAbs) and nanobodies (Nbs) (A) HCAb (middle) consists of 2 heavy chains only. Its antigen binding part is a VHH and a single amino acid chain of ~120 aa (15 kDa). (B) CDR (complementarity determining regions, red) and FR (framework regions, blue) of a nanobody. The CDRs are important for antigen binding and are usually longer than their IgG counterparts, allowing nanobodies to access difficult to reach epitopes, such as enzyme catalytic sites.

Discover the many capabilities of recombinant 15 kDa high affinity VHHs/nanobodies.

  • Broad application range in (bio) medicine/pharmacology and way beyond.
  • Key features: tremendous engineering versatility, unparalleled control, small size, single domain nature. Manageable in every respect.
  • Seamless and affordable expression in prokaryotes, a simple carbon source suffices, no FBS.
  • Straightforward nanobody derivatization, ready for click chemistry with a variety of chemicals and biologicals, site specifically.
  • Every protein is a potential target for manipulation/drugging.
  • Nanobodies are the fastest way to drug any target protein or to deliver a drug as an ADC.
  • Equip your lipid nanoparticle (LNP) with a nanobody and endow it with unprecedented directionality.
  • Multimodal target regulation: block, perturb, degrade (cf siRNA/shRNA), image, trace, crystalize, ectopically locate your protein of interest. All with one tool! In vitro and in vivo.
  • Tap into our > 25 years experience.

Gulliver Custom Services

  • Custom nanobody generation.
  • Nanobody library construction.
  • Deliverable: nanobody cDNA clones, recombinant nanobodies.
  • Modifying nanobodies for coupling to drugs, to Lipid nanopoarticles (LNP), quantum dots, magnetic beads.
  • Time frame: 6 weeks immunization + 3 weeks processing: cDNAs ready.
  • Get in touch with our scientists to realize your custom VHH project. Click here for entering information on your antigen and request a quote, or mail info@gulliverbiomed.com

The breadth of nanobody applications

Biomedical Research In Health & Disease

In a nutshell

More Affordable & Sensitive Diagnostics

In a nutshell

Minimal Linkage Error In Microscopy

In a nutshell

Cytology – VHH intrabodies

In a nutshell

CAR-T: improved VHH solubility

In a nutshell

VHH Gene Therapy (small size)

In a nutshell

Novel Antibiotics

In a nutshell

Crop protection (fungi, bacteria, viruses)

In a nutshell

Food Safety

In a nutshell

Antibody drug conjugates

In a nutshell

Homing device on Lipid nanoparticle

In a nutshell

Add your own Personal discovery

In a nutshell

Generate VHHs against your target(s) of interest and magnify your research potential

Include this technology into your next grant application or better even, contact us today. We guide you through the process, keep you up to date and help you further once you obtain your VHHs of interest. Our academic branch researchers have more than two decades of experience in applying them in research.

  • Engineer nanobodies like any other cDNA: clone VHH into an expression vector, add any tag, transform, transfect, transduce, nucleofect, electroporate… your nanobody into a prokaryotic host or into eukaryotic cells and modulate properties of the antigen.
  • Experiments in cells: no need to overexpress your protein of interest (POI) as a GFP fusion protein: instead trace POI in living cells by coupling a nanobody to a fluorescent protein.
  • Ectopically ocalize POI to other cellular compartments (nucleus, mitochondria, peroxisomes, endoplasmic reticulum…).
  • Eradicate POI from cells (protein knock-out) through degradation via the proteasome. As revolutionary as RNAi in 2001.
  • Use VHH as a chaperonefor co-crystallization to obtain atomic resolution information on the epitope interface. This can be a stepping stone to development of a small compound inhibitor via medicinal chemistry.
  • Turn VHH into a diagnostic or a tracerby labeling with a radionuclide
  • Proteomics, screen for interaction partners, or loss of interaction partners (nanobodyfootprinting).
  • Insert unnatural amino acid and endow VHH with unique chemical reactivity (i.e. azido-Phe).

Whether you are working in fundamental or applied (bio)medicine, animal or plant sciences, pharmacology, virology, microbiology, (super-resolution) microscopy, vaccines, fisheries, VHHs offer many opportunities to uncover biological/clinical information that cannot be achieved by using either conventional genetic approaches or conventional antibodies. The reason is that proteins are essential building blocks in every living organism and contribute to health and disease in the most fundamental manner.

Genetic approaches invariably result in eradication of all functions of the protein of interest as well as obliteration of its entire interaction network. Proteins have many associates, building an interaction network that supports many cellular functions. Implementing VHHs/Nanobodies in your research adds a new level to your project and enables you to ask new questions that you were not able to answer before and address them experimentally.

Key examples where VHHs typically outperform IgGs

  • Concatenation: increase binding strength, or target two different antigens at once. Such bispecific or bivalent nanobodies can be expressed/purified from prokaryotes.
  • Flexible modulation of circulation time. VHHs are quickly cleared from the circulation via the kidneys. Couple the VHH to an Fc region to increase circulation time. Alternatives include PEGylation, coupling VHHs to albumin-binding VHH.
  • Diagnostics/Biosensors: oriented immobilization of VHH onto support; better reproducibility and increased sensitivity.
  • Recombinant VHH-reporter cassette: couple primary VHH directly to reporter enzyme. High expression of fusion protein in mammalian cells. No secondary Ab required.
  • Intrabody: the intracellular localization of a protein can be altered by transfecting a VHH against antigen, equipped with a targeting sequence, i.e. towards outer mitochondrial membrane (MOM – green color in figure). The antigen will be forced to locate at mitochondria (red), and will co-localize with antigen (yellow, right). This also proves that VHH is functional in the cytoplasm. Apart from this, the nanobody can of course be used for perturbation of POI biological activities or interaction with other proteins or with DNA (i.e. transcription factor).
  • Gene therapy : multiple copies of identical or different VHHs can be easily accommodated into a viral genome due to their small size (0.36 kb).
  • Nanobody derivatization: click a broad range of different compounds onto VHHs, site specifically, via an azido-phenylalanine.

NANOBODY BENEFITS, SUMMARY:

  • 10x smaller than IgGs.
  • Long CDRs for blocking enzymes or perturbing protein-protein interactions in vitro and in vivo.
  • Great tool for proteomics.
  • Inhibitors against structural proteins mostly unavailable – nanobodies fill this gap.
  • Subtle blocking of protein functions rather than blasting the POI to smithereens with RNAi.
  • Understand the biology of your protein target in greater detail.
  • Nanobodies are stable in the cytoplasm of cells (reducing environment).
  • Nanobody cDNA always available, by default.
  • Circumvent GFP-fusion protein overexpression and unbalancing protein homeostasis.
  • Target the endogenous protein when used as intrabody.
  • High affinity binders (nanomolar to picomolar).
  • Imaging your target remains possible (not with RNAi).
  • Insert unnatural amino acids in their primary structure, site specifically.
  • Site specific coupling of fluorophores, minimal linkage error for super res microscopy.
  • Click nbs covalently to fluorophores, magnetic beads, gold nanoparticles, biologicals, drugs.
  • Nanobodies are conducive to protein crystallization.
  • Identify important epitopes in the protein of interest.
  • Drug ‘undruggable’ proteins.