Adoptive cell therapy (ACT) has emerged as a highly effective treatment for cancer, particularly for patients with limited treatment options. This innovative approach harnesses the patient’s own immune system to target and attack cancer cells. One form of ACT, known as Engineered TCR therapy, utilizes engineered T cell receptors to specifically target tumor-specific antigens. The process begins with sequencing tumor biopsy samples to identify tumor mutations and analyzing peripheral blood to uncover the TCR repertoire.

TCR repertoire sequencing can be achieved through two main methods: single-cell sequencing and bulk sequencing, each offering unique advantages. Bulk sequencing allows for a broader sampling of the sequence space, but it comes at the cost of losing information about the alpha-beta TCR pairing. On the other hand, single-cell sequencing captures detailed information about alpha-beta chain pairing and receptor composition, but it has a lower throughput compared to bulk sequencing.

The key benefits of Twist’s technology in this context include high diversity and quality in TCR libraries. Combinatorial assemblies can encompass up to 10,000 gene fragment combinations, ensuring a rich and varied representation. NGS-verified libraries guarantee that over 90% of possible variants are present within 10 times of the mean, ensuring reliability and accuracy. The platform also offers customization, allowing users to define combinatorial variants across alpha and beta chains in TCR Libraries.

Twist’s technology is flexible, accommodating sequences up to 1.5 kb in length, and it is designed at scale with diversity across multiple elements of the sequence. This flexibility, combined with high diversity and quality, positions Twist as a valuable partner in advancing Engineered TCR therapy, providing researchers with the tools needed for comprehensive TCR library customization and optimization.

Introducing the Spread-Out Low Diversity (SOLD) libraries – the latest tool revolutionizing the mapping of protein sequences and exploring the intricate relationship between proteins and their environment. Designed for researchers seeking efficiency, precision, and cost-effectiveness, SOLD Libraries offer a streamlined approach to investigating combinatorial possibilities.

These libraries stand out with their unique features, providing greater flexibility compared to traditional methods. Suitable for sites with scattered diversity, SOLD Libraries require no template, offering a novel and efficient solution. The precision of SOLD Libraries is unparalleled, ensuring no premature stop codons or unwanted codons, along with precise control over amino acid and codon distribution. This precision surpasses traditional methods such as NNK, TRIM, and epPCR.

Ensuring superior quality, all SOLD Libraries undergo NGS verification of modified regions, rigorous quality control, and verification of all variants. Created using Twist’s patented silicon-based synthesis platform, SOLD Libraries guarantee low error rates, making them cloning-ready and a reliable tool for researchers exploring the variant space. SOLD Libraries provide the ultimate combination of flexibility, precision, and quality for an advanced and efficient protein sequence mapping experience.

The utilization of single-site variant libraries is proving invaluable for researchers aiming to delve into a protein’s sequence space and understand the intricate relationship between sequence, protein structure, and function. This innovative approach allows for a comprehensive exploration of variants, providing crucial insights into the molecular dynamics of proteins.

The construction of Twist Site Saturation Variant Libraries takes protein engineering to the next level. Leveraging advanced massively parallel oligonucleotide synthesis through Twist’s proprietary silicon-based DNA synthesis platform, these libraries ensure a precise and controlled crafting of variants. With complete mastery over codon usage, high uniformity at each site, and rigorous quality control verified through next-generation sequencing (NGS), these libraries offer researchers the flexibility to conduct experiments with ease. Whether opting for one position per well in a 96-well plate or pooling all positions in a single tube, this methodology enables the screening of 1 to 20 different amino acids at each position, further enhancing the adaptability and efficiency of protein engineering studies.