Genes
Oligo Pools
NGS
Variant Libraries
Synthetic Controls
Antibody Discovery
IVDR Solutions
- OVERVIEW
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Precision Variant Library Technology Allows for Focused Screening
Twist’s massively parallel silicon-based DNA synthesis platform produces highly uniform and accurate oligos, with 90% of oligos represented within <2.5x of the mean, along with an industry-leading low error rate of 1:2,000 nt.
Combined with our well established molecular biology expertise, the Twist oligo synthesis platform enables the fabrication of highly diverse gene mutant libraries with excellent variant representation and highly specific user-defined composition with no unwanted bias or motifs. Twist library technology enables a comprehensive interrogation of the variant sequence space.
KEY BENEFITS
High Diversity Precision
- Effortlessly incorporate multiple variant domains into one or multiple scaffolds
- Precise control over codon usage (all 64 codons), amino acid distribution, and length variation
Verified Quality
- Rigorous quality control, including NGS verification of modified regions
- Sequence variant ratios documented
- Uniform distribution of user-defined variants
- No premature stop codons or unwanted codons
Flexibility
- Design all sequences, single or multiple domains and combinations— single, pairwise, or triple variants
- Modular synthesis system enables iteration of future libraries
- Greater flexibility than TRIM and the degenerate approach
Precision Variant Library Technology Allows for Focused Screening
Learn more about Twist Bioscience’s ability to construct complex, high diversity libraries at confined regions (for example, CDRs) and introduce technology advancements that enable the construction of synthetic DNA libraries with diversity scattered along the length of constructs.
Did you know that ionic charge can affect antibody-target binding?
Learn how Twist helped a leading pharmaceutical company precisely interrogate key residues involved in both target recognition and antibody charge by synthesizing combinatorial variant libraries.
Introducing the new Library Design Tool
Streamlined Library Design at Your Fingertips
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 Precise 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.
Cloning Option For Libraries
Our platform enables uniform synthesis of highly complex oligonucleotides which minimizes potential bias in the downstream workflow. Our team of scientists have developed a strategy to maintain that uniformity throughout library fabrication and cloning. These are steps in the workflow that have been commonly shown to introduce bias which can lead to some variants showing up disproportionately in screens/assays. By maintaining the starting uniformity and minimizing the dropouts as well as under-represented variants, our cloned libraries are able to maintain a high level of diversity which helps reduce screening time and effort.
The figure shows the observed amino acid distribution at each variant position after fabrication (linear) and after cloning as it compares to the desired frequency (expected)
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 four sites of a mutagenic domain after library linear assembly and after cloning. The expected columns for each position shows the desired frequency of each amino acid substitution. This data shows that all expected variants were present at all positions, and uniformity was maintained throughout assembly and cloning.
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A New Way of Designing Your Libraries
The New Library Design Tool is your all in one solution to streamline, optimize, and expedite the DNA Library design and ordering process.
Design Companion
- Intuitive, interactive portal to easily upload your library sequence file
- Identify potential errors in sequence with instant feedback enabling library validation on the fly
- Save drafts for future reference
Real-time Optimization
- Errors are flagged for review, letting you quickly resolve issues without delays
- Our library design experts are still ready to assist you with any questions
- With our intuitive tool and expert support we can help you find the fastest path to a validated, high-quality library
Faster Process
- Real-time, interactive library design interface supports optimizing your library design and cost efficiently
- Save drafts for future reference
- Automatically generates a Statement of Work (SOW) for your order, expediting the entire ordering process
Expert Support Still at Your Fingertips
If you have any questions,please feel free to email us at library@twistbioscience.com
Take a peek at our Library Design Tool
A New Way of Designing Your Libraries at Twist
Watch Step by Step how to optimize your sequences
START DESIGN NOW
Let’s get Started
The New Library Design Tool is your all in one solution to streamline, optimize, and expedite the DNA Library design and ordering process.
Step 1
Log into your account. If you don’t have one, it only takes a few minutes to set it up!
Step 2
Start to design your library in the new interactive libraries design tool which has a step by step “how to” wizard. With this option you can optimize your library in real time with validations on the fly and real-time pricing and receive an SOW at the end of the submission process.
Step 3
Once the quote is accepted by the customer, the Libraries Team will send the project to the production team
Note:
The Libraries Design Tool is not currently available in the APAC region. Please check with your local support team on availability date.
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