OVERVIEW PROOF OF CONCEPT RESOURCES
OVERVIEW

GPCRs are ubiquitous in human biology, participating in diverse processes such as metabolism, inflammation, neurotransmission, and carcinogenesis. The Twist GPCR Library Series leverages all known GPCR-ligand interactions and existing GPCR antibody diversities to enable antibody discovery beyond existing GPCR-targeting small molecules and antibodies, which cover only 13% of the human GPCRome.

The GPCR 2.0 scFv Library integrates all known GPCR interactions with over 150,000 GPCR-binding motifs, including protein ligands, peptide ligands, peptide mimics GPCR N-terminal domains and extracellular loops, and GPCR-binding antibodies.

The GPCR 3.0 scFv Library incorporates diversities from all known GPCR antibodies. Modeling based on 61 GPCR antibody sequences targeting 22 different GPCR proteins informs the design of this library.

VHH hShuffle GPCR Library The VHH hShuffle GPCR Library has a diversity of 1x1010 and transfers design elements from the GPCR 2.0 scFv Library to the highly desirable VHH format, providing access to occluded epitopes and simplifying downstream engineering and manufacturing.

 

> 100,000 Different GPCR Binding Motifs

With over 100,000 different GPCR binding motifs, unlock the discovery of antibodies to this difficult-to-target class.

 

GPCRs are Hard-to-Drug
 
  • 30-50% of current drug targets are GPCRs but there are only 2 FDA approved antibodies

  • Current antibody drug development methods do not work

  • Random mutagenesis libraries are too inefficient to explore the effective 
sequence space
     
Synthetic Library Advantage
 
  • No immunization required
  • Synthetic mAb libraries focus on effective sequence space
  • Simultaneous screening against multiple targets
GPCR Binding Motifs
> 100,000 Different GPCR Binding Motifs

With over 100,000 different GPCR binding motifs, unlock the discovery of antibodies to this difficult-to-target class.

 

GPCRs are Hard-to-Drug
 
  • 30-50% of current drug targets are GPCRs but there are only 2 FDA approved antibodies

  • Current antibody drug development methods do not work

  • Random mutagenesis libraries are too inefficient to explore the effective 
sequence space
     
Synthetic Library Advantage
 
  • No immunization required
  • Synthetic mAb libraries focus on effective sequence space
  • Simultaneous screening against multiple targets
GPCR Binding Motifs

GPCRs are ubiquitous in human biology, participating in diverse processes such as metabolism, inflammation, neurotransmission, and carcinogenesis. The Twist GPCR Library Series leverages all known GPCR-ligand interactions and existing GPCR antibody diversities to enable antibody discovery beyond existing GPCR-targeting small molecules and antibodies, which cover only 13% of the human GPCRome.

The GPCR 2.0 scFv Library integrates all known GPCR interactions with over 150,000 GPCR-binding motifs, including protein ligands, peptide ligands, peptide mimics GPCR N-terminal domains and extracellular loops, and GPCR-binding antibodies.

The GPCR 3.0 scFv Library incorporates diversities from all known GPCR antibodies. Modeling based on 61 GPCR antibody sequences targeting 22 different GPCR proteins informs the design of this library.

VHH hShuffle GPCR Library The VHH hShuffle GPCR Library has a diversity of 1x1010 and transfers design elements from the GPCR 2.0 scFv Library to the highly desirable VHH format, providing access to occluded epitopes and simplifying downstream engineering and manufacturing.

 

PROOF OF CONCEPT
Multiple Antibodies Bind GLP1R Over-Expressing CHO Cells and are Functional in a cAMP Assay
  • IgGs are monomeric and not prone to aggregation
  • Multiple FACS positive hits include GLP-1 and GLP-2 motifs as well as
    additional unique sequences.
GPCR Cellbinding
Multiple Antibodies Bind GLP1R Over-Expressing CHO Cells and are Functional in a cAMP Assay
  • IgGs are monomeric and not prone to aggregation
  • Multiple FACS positive hits include GLP-1 and GLP-2 motifs as well as
    additional unique sequences.
GPCR Cellbinding
RESOURCES
Quickly find dozens of antibodies
Quickly find dozens of antibodies
Quickly find dozens of antibodies