Choose the fastest and most efficient way to get your nanobody production thanks to our unique antibody phage display libraries and expertise! Our advanced monoclonal antibody production platform offers the possibility to produce your own alpaca, camel, or llama VHH against any type of antigen and without any restriction of use. Our unique platform of antibody phage display adapted to therapeutic applications ensures you always receive the most relevant binders for your target and application.

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Developing Nanobodies? Discover our proprietary Premium LiAb-VHHMAXTM library

  • 1.51×1010 variants
  • 57 animals: 16 alpacas, 10 camels, 31 llamas
  • Ideal for cryptic epitopes and therapeutic applications
  • Easy production in bacterial expression system
  • VHH format
  • In-licensing kits available

Our antibody phage display service process

Antigen design

  • Hapten
  • Peptide
  • Protein
  • Whole cell

Immune library

Immune library construction

  • PBMC isolation
  • RNA extraction and cDNA synthesis
  • VH and VL PCR amplification
  • Library construction and QC

Antigen design

  • Hapten
  • Peptide
  • Protein
  • Whole cell

Naive library

Library screening and biopanning

  • Screening of naive or immune library against antigen
  • 4-6 rounds of biopanning

ELISA screening of single phage binders

  • ELISA screening and validation until identification of at least 3-10 different binders

DNA extraction & antibody sequencing

VHH engineering (optional)

  • Antibody affinity maturation
  • VHH humanization
  • Antibody conjugation
  • Bispecific antibody development

Advantages of nanobody production

Nanobodies present numerous advantages to be exploited for therapeutic, diagnostic, and research applications. This includes:

  • Easy production: in contrast to N-glycosylated full-length monoclonal antibody production which is generally done in mammalian cells, VHH can be produced in microbial expression systems such as E. coli or yeasts. Production in E. coli is generally done by secretion in the oxidizing periplasmic space in order to avoid additional refolding step.
  • Low immunogenicity: VHH present a low immunogenicity thanks to their small size and to their high sequence homology with human VH gene family III.
  • Good tissue penetration: the small size of VHH antibodies allows them to easily pass through barriers and penetrate tissues. Thus, these small size antibodies can access targets that would not be reachable by full-length antibodies.
  • Ability to recognize a wide variety of epitopes: VHH antibodies have the ability to recognize epitopes deeply buried in antigens.
  • High stability: The high stability of VHH allows for their use in various applications such as capturing reagents or biosensing.

Nanobody production for therapeutic applications

Nanobodies offer several advantages compared to full-length antibodies. The advantages discussed above, pave the way to the development of new therapeutics.

Coupled with the screening power of the phage display technology, nanobodies can be generated against a multitude of antigens with different properties. Despite proteins and peptides being the most widely used antigens for nanobody production, there is an increasing interest in generating nanobodies against untapped epitopes.

Some of these untapped epitopes are typically hard to target due to their structural complexity; however, if cell-based phage display is used for nanobody generation, many new biologically relevant treatments can be brought to the clinic.

Anti-cancer Therapies

Full-length mAbs are traditionally used for their ability to evoke ADCC or CDC via their Fc receptor domain. These properties are highly desirable when developing monoclonal antibody therapies for cancer.

However, their large size becomes a disadvantage when it comes to difficult-to-reach targets. In contrast to full-length IgGs, nanobodies cannot evoke ADCC or CDC but can be used as antagonistic drugs to immunomodulate and control tumor cell proliferation and can induce apoptosis.

Other promising approaches include the conjugation of nanobodies to various entities such as effector domains, radionuclides, or even small molecule covered nanoparticles.

Anti-infectious Treatments

VHH can prevent the spread of viruses by interfering at different steps of the viral replication cycle. Intrabodies also represent a promising approach for their capacity to target virus replication at an early stage. However, the feasibility of this approach in patients limits its use. For this reason, coupling of nanobodies with cell penetrating agents were developed (e.g. anti-HCV nanobody-penetrating conjugate).
Nanobodies can also be used to combat bacterial infections. Several elegant strategies implying the use of VHH were already developed.

  • Blockage of the bacterial attachment to host cells: VHH can interfere with bacterial attachment to host cells by binding onto bacterial surface proteins.
  • Limitation of bacterial motility: targeting bacteria’s flagella is a good option to limit bacterial motility. To do so, a well described approach consist in the production of pentameric flagella-specific VHH. This strategy limits the colonization ability of bacteria.
  • Limitation of bacterial resistance to antibiotics: nanobodies can be used to interfere with enzymes conferring an antibiotic resistance to bacteria. This original strategy has been used for the development of an antibody directed against β-lactamase, conferring resistance to β-lactam antibiotics to bacteria. Administrating an anti-β-lactamase in combination of a β-lactam antibiotic increases the efficacy of the antibiotic treatment.

Nanobodies To Treat Neurodegenerative Disorders

Up to date, there is no treatment to cure neurodegenerative diseases. Only symptomatic treatments are available on the market. Thanks to their unique selectivity and their capacity to cross the blood-brain barrier, nanobodies represent an interesting approach to overcome these challenges. Several trials involving nanobody production to cure Alzheimer’s disease are already well documented. Even though its origin is still not well understood yet, several hypotheses about Alzheimer’s disease pathogenesis exist. One of them involves the deposition of extracellular amyloid plaques leading to neuronal death. Thus, several biomolecules involved in amyloid plaques formation were considered as potential nanobody targets. This includes free Aβ peptide or BACE-1…
Similar strategies were employed to target α-synuclein to cure Parkinson’s disease. Parkinson’s disease is characterized by misfolding of α-synuclein leading to the formation of aggregates and ultimately to death. Up to date, no solution allowed preventing α-synuclein aggregation but nanobodies remain a promising therapeutic approach.
This list is only a non-exhaustive overview of the nanobodies’ potential as a therapeutic agent. Other applications were already explored such as anti-inflammatory or anti-infectious treatment..

Camelid antibody production for diagnostic applications

Camelid antibody production is also highly relevant for diagnostic applications such as imaging. The small size of VHH confers them unique advantages compared to conventional full length antibodies:

  1. They are weakly immunogenic
  2. They bind rapidly and specifically to antigens.
  3. Their short blood circulation time induces a rapid high signal-to-noise ratio.
  4. They demonstrate efficient tissue penetration and access to epitopes that would not be accessible to conventional antibodies.

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