AI Hypermutated scfv Library

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OVERVIEW
SPECIFICATIONS
THE PROCESS
PROOF OF CONCEPT
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Unleash the Power of Artificial Intelligence

The Twist AI Hypermutated scFv Library uses the power of artificial intelligence to augment the design of a synthetic antibody library with fully human antibody sequences. A neural network mimics B-cell receptor recombination and hypermutation, producing antibodies with developability in mind.

This unique library can empower your therapeutic antibody discovery and development for any indication.

Produce scFv antibodies optimized for development

Proven, highly manufacturable framework built on multiple backbones and optimized for functionality
Fully human antibody sequences
1 x 109 diversity

Unlock unique yet natural antibody repertoires with AI

Design algorithm trained on millions of antibody sequences
AI mimics natural B-cell receptor development
Capture the diversity produced by rearrangement and hypermutation

Synthetic library advantage

Panning to functional assays in 10-12 weeks without immunization
Focus on effective sequence space
Screen multiple targets simultaneously

Library Specifications

Designed using deep learning, the Twist AI Hypermutated scFv Library provides a versatile platform for antibody discovery. The neural network used to design the library mined millions of antibody sequences to generate diverse antibody repertoires in a process that resembles natural B-cell receptor hypermutation and recombination.

The library limits diversity in complementarity-determining regions 1 (CDR1) and 2 (CDR2) while maximizing that of CDR3. Four combinations of heavy chains and light chains (VH3-23/VK1-39, VH3-23/VK3-20, VH1-69/ VK1-39, and VH1-69/VK3-20) each incorporate 200 linked HCDR1-HCDR2 sequences with 100,000 HCDR3s, and 100 linked LCDR1-LCDR2 sequences with 10,000 LCDR3s. Combinatorial assembly results in a fully human scFv library with 400,000 HCDR3s, 40,000 LCDR3s, and a diversity of 1 x 109.

CDR Length Diversity Matches Human Repertoire Distribution

The sequences in the AI Hypermutated scFv library are computationally derived using a carefully selected subset of a full database of naturally occurring human antibodies. For CDR1, CDR2, and CDR3 of IGHV3-23, the length distributions of the selected antibody sequences (purple) closely mimic the natural human antibody repertoire (black).

Library Panning & Screening Process

Go from panning to functional assays in 10–12 weeks. The process starts with phage screening the diverse Twist Minotaur scFv Library against target antigens and ends with reformatting candidate antibody fragments to full-length IgG.

You can also license the Minotaur scFv library to initiate your own in-house discovery projects. To learn more, get in touch at biopharma@twistbioscience.com

Proof of Concept Data

The Twist AI Hypermutated scFv Library was successfully panned against SARS-CoV-2 Spike Protein S1, a key protein on the surface of the coronavirus, to identify unique clones with desirable properties. Affinity was determined via surface plasmon resonance and activity was demonstrated in competition assays.

Kinetics with Directly Coupled Anti-S1 Antibodies

The AI Hypermutated scFv Library effectively uncovers SARS-CoV-2 S1 antibody leads with high binding affinities.

Potent Inhibition of VERO E6 Cells by FACS

A panel of anti-S1 antibodies from the AI Hypermutated scFv library shows inhibition of S1 binding to ACE2-expressing VERO E6 cells. A flow cytometry plot for representative clone TB268-14 illustrates a shift in the transfectant population compared to the parental population.