Variant Libraries
Twist Bioscience - Dedicated to creating well-designed, highly diverse libraries to ensure that you uncover more of what you want and only what you want.
Complex Custom Libraries
Twist’s proprietary oligo synthesis technology offers a unique approach to library creation. The silicon-based synthesis platform generates high-quality oligo pools, which are used to build fully-customized, user-defined variant libraries on a single chip. Twist's unparalleled platform also enables the creation of thousands to billions of specific variants. You can be assured exactly what you design is exactly what you get.
High Diversity Variant Domains
Twist has developed high fidelity methods for precisely splicing large pools of oligonucleotides (with composition and length variation) to create NGS verified combinatorial diversity of up to 10^10 unique variants within a single domain. Every variant is designed in-silico and screened prior to synthesis, eliminating unwanted sequence bias, premature stop codons, and undesirable motifs.
DATA
High Quality Data
Twist Bioscience’s silicon-based DNA synthesis platform and library technology provides scientists with high-quality libraries that produce reliable data in less time. When compared to two other competing technologies (figure 1), Twist’s library showed less than 1% deviation from the designed amino acid frequency. In addition to precisely matching designed amino acid ratios, Twist’s in-silico DNA synthesis platform seamlessly incorporates desirable binding motifs and length variation across multi-domain libraries, giving scientists the power to precisely design and customize variant libraries that enable a comprehensive analysis of the variant space.
And with Twist libraries, the problems and challenges typical of NNK and TRIM libraries are avoided. Each variant is printed base-by-base and screened prior to synthesis, eliminating stop codons, liability motifs, unwanted mutations, and any undesirable biases, all at the beginning of the process. As a result, the library is enriched for the requested functional variants and the screening burden is reduced..
Our industry-leading, ready to use, highly-diverse and precisely designed libraries give scientists more opportunities to achieve their research goals.
Superior Libraries
At Twist, we use molecular biology expertise to precisely construct variant libraries. Our single-base control approach allows us to deliver high-diversity libraries without motifs that could confound your screening process. We deliver fully-customized libraries of unparalleled quality, with desired variants present at user-defined rations. Here you can see a CVL example representative of that quality. Variants in seven sequential amino acid positions were generated and all have expected variants at the positions shown, with nearly all at the desired ratio:
At position 1 and 6, the wild type amino acid was requested at 40% (position 1) and 30% (position 7). The remaining 18 amino acids were all requested to be low as 3.3%.
At position 3-5 amino acid residues were requested and observed at 5.3%.
User-Defined CDR Libraries
Our user-defined Variant Libraries allow you to choose what unique CDR (complimentary defining regions) sequences you want to be incorporated into the choice of framework(s).
Each CDR can be codon-optimized to avoid the creation of unwanted restriction sites. Machine learning has become an integral part of scientific research and has been used as a tool to analyze antibody libraries and identify unique CDR combinations that would yield, for example, higher affinity and specificity.
Coupled with Twist’s silicon-based synthesis platform, explicit library combinations generated from the analysis can be synthesized and seamlessly incorporated into a fully synthetic library to refine the exploration of the variant space.
Libraries QC’d with NGS
Since every Libraries verified with NGS, negative data can be used to identify mutations that do not yield improved functions, and those can be removed in the next iteration of library design.
The table shows the amino acid frequency (%) at seven sites of a mutagenized region synthesized using. Variants in seven sequential amino acid positions were generated with 19 amino acid residues (cysteine was omitted) in the first seven sites. A tabulated frequency data obtained from NGS, with the shade of green indicating deviation from the expected value. All expected variants were present at all positions and their observed frequency was within 25% of the expected value (specification) at 5.3%.
