How it Works

Input antibody sequence into software

Order oligo pools & template DNA

We create your library & screen 
against target

Why Twist Antibody Optimization (TAO)?

Use natural human antibody sequence data to create
an optimization library that exactly matches the human
repertoire

  • Liabilities are removed, e.g. isomerization, cleavage, deamidation, glycosylation sites, liability dipeptide motifs
     
  • Rational sampling from desired sequence space
     
  • Accurate representation: motif sequences explicitly encoded in oligos
antibody-cdr-structure
TAO process

Optimize for

  • Affinity (pM)
  • Half-life
  • Expression
  • Immunogenicity
  • Solubility
  • Druggability
  • Processability

TAO Circular Dendrogram

TAO-optimized IgGs demonstrate 100x improvement in monovalent binding affinity

compared to the parental sequence. These high-affinity binders each contain unique

CDRH3 and are not clustered by sequence lineage.

Download the Poster 

TAO Optimized IgGs show improved binding affinity

After Twist Antibody Optimization, binding affinity went up 72× , function increased by 9.5×

Download the Product Sheet 

TAO KO
TAO KO

Multiple Optimized Leads

Addition of anti-PD1 antibody blocks the PD-1/PD-L1 interaction, releases inhibitory

signal and results in TCR activation and NFAT-RE-mediated luminescence (RU)

Download the Product Sheet 

The TAO process

STEP 1

DNA Library Generation
 

STEP 2
 

Phagemid Library Construction

STEP 3

Panning & sequencing

STEP 4

Screening

STEP 5

IgG reformatting, expression & characterization

STEP 6

IgG screening

 

 

 

STEP 1

DNA Library Generation

  • Optimization library design and generation
  • Analysis of parent antibody sequence with TAO software platform
Biopharma Step 1

 

 

 

STEP 2

Phagemid Library Construction

  • Cloning of DNA library into phagemid vector for phage library generation
  • Library QC for display/diversity by Sanger sequencing of multiple plates

Biopharma Step 2

 

 

 

STEP 3

Panning and sequencing

  • Up to 5 rounds panning using bead-based, cell-based, or immobilized antigen methods
  • Enrichment analysis by NGS of VH repertoire following each panning round
Biopharma Step 3

 

 

 

STEP 4

Screening

  • High-throughput phage ELISAs
  • Positive clones from R4/R5 sequenced and re-arrayed for gene synthesis
  • For cell-based targets, all sequence-uniques carried forth for screening later as IgGs (if not screened at this stage in scFv or fab formats)
Biopharma step 4

 

 

 

STEP 5

IgG reformatting, expression, and characterization

  • VH/VL sequences synthesized in desired isotype variant expression vectors
  • DNA scale-up, expression in 10-mL expi293, purification, QC by CE-SDS, SEC
Biopharma step 5

 

 

 

STEP 6

IgG screening

  • Carterra kinetics studies for soluble antigens
  • FACS binding experiments for cell-based antigens
  • Positive binders tested in functional assay
Biopharma step 6

Interested in partnering with us?

 

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