There are many factors to consider when bringing oligonucleotide synthesis in house beyond simply selecting and ordering an instrument. This guide highlights what these factors are, from space and throughput considerations to tips for organizations that have low to no experience conducting organic chemistry in their facility, to help you ensure a smooth and successful oligo synthesis production setup.

This guide from LGC Biosearch Technologies discusses considerations for bringing oligonucleotide synthesis in house to secure the supply chain, speed turnaround time, protect intellectual property, or control costs.

The new era of personalized health relies on data to guide more personalized patient treatments, therapeutics, diagnostics, and patient care. Across clinical and research disciplines, leading healthcare and life sciences organizations are combining varying data modalities to increase the accuracy of diagnoses, reduce turnaround times, and ultimately improve patient outcomes.

This white paper from Amazon Web Services presents case studies in which companies, hospitals, and organizations partnered with AWS for Health to unify analysis of various forms of medical and omics data and help researchers and clinicians generate new insights and offer more personalized care.

Precision oncology approaches have made great strides harnessing individual tumor mutation profiles to guide targeted therapy choices. However, deeper molecular insights are needed to improve personalized treatment decisions that are tailored to specific molecular characteristics of a tumor. Integrating gene expression analysis in personalized oncology provides an additional level of insight that cannot be provided by genomic data alone. These analyses include evaluating expressed mutations and drug targets, novel gene fusions, clinically relevant signatures, and the tumor immune microenvironment (TME).

Comprehensive molecular tumor analysis (CMTA) is an NGS-based tumor diagnostic test developed by Alacris Theranostics. The test integrates whole exome and transcriptomic sequencing (WES and RNAseq) and is deployed as an end-to-end accredited diagnostic platform from tumor sample uptake (FFPE or frozen) to personalized clinical interpretation reports. Designed to serve all cancer patients, CMTA is a tumor-agnostic test that displays a unique molecular view of each sample and is particularly well-suited to refractory cancers with complex patterns or tumors of unknown origin.

In this webinar, Alacris Theranostics will discuss the benefits of comprehensive tumor profiling in clinical settings and present the strategy implemented in their bioinformatics pipeline to identify cancer-relevant somatic events. In addition, the diagnostic company will share how they use QIAGEN Clinical Insight (QCI) Interpret to annotate variants and identify potential therapeutic entry points.

Precise tagging of genes via the homology-directed repair pathway is a versatile approach for studying gene function. Advances in genome editing technologies such as the CRISPR-Cas9 system have allowed researchers to target nearly any gene for modification. However, the efficiency of integrating large DNA molecules into the mammalian genome via HDR is inherently low.

This application note from Thermo Fisher Scientific describes a simple method for efficiently tagging endogenous genes using donor DNA prepared with the Invitrogen TrueTag Donor DNA Kit, GFP, with broad applications in general genome engineering, protein production, and immune cell therapy.

CRISPR gene editing technology has the potential to transform research at an astonishing rate. The rate of success is dependent upon many factors, such as gRNA design, Cas9 efficiency, and delivery conditions.

This application note from Thermo Fisher Scientific demonstrates an end-to-end workflow, from T-cell isolation and activation to gene editing, that demonstrates over 90 percent functional knockout of the T-cell receptor in donor-derived primary T-cell populations.

CRISPR-mediated genome editing is an extremely powerful tool that enables researchers to create different cellular models by removing, adding, or altering sections of a DNA sequence in the genome in a wide range of different cell types and gene loci. While it can achieve high editing efficiencies, the CRISPR-Cas9 system can also cleave the target DNA at unintended locations (known as off-target events) that can result in undesired phenotypes or loss of functional gene activity, which is especially detrimental for therapeutic applications.

This white paper from Thermo Fisher Scientific discusses strategies to optimize the various factors that cause off-target events, describes an unbiased analysis system, TEG-seq, to help detect off-target events, and describes the use of this system to screen for a high-fidelity Cas9 mutant with improved specificity.

To help researchers in their quest to understand how the genome influences phenotype, we’ve developed a complete guide to trusted methods and solutions for every step in the genome editing workflow.

Advances in genome editing have the potential to change the way we create energy, produce food, optimize industrial processing, as well as detect, prevent, and cure diseases. Through innovative design and engineering, this unique science enables researchers to study, alter, create, and reconstitute highly complex pathways, DNA sequences, genes, and natural biological systems. With a better understanding of life’s most challenging biological questions, we can uncover answers to improve the human condition and the world around us. We’ve created this resource to explain the cell engineering methods and technologies available today, and to guide you in choosing the solutions you need to break through to discovery faster.

Genome editing technologies have given investigators the power to unlock a variety of new applications and experimental approaches. While gene knockouts have been achievable for several years, successful gene knock-ins have remained elusive due to the low efficiency of homology-directed repair (HDR). Successful knock-in experiments depend on the design of the donor DNA, the effectiveness of the single guide RNA (sgRNA) and Cas9 ribonucleoprotein (RNP) complex, and the efficiency of delivering materials into the target cells.

This application note from Thermo Fisher Scientific describes two use cases for the Invitrogen TrueDesign Genome Editor, a free online tool for designing and ordering materials for knock-in CRISPR–based editing: introduction of an SNP change in the LRRK2 gene in induced pluripotent stem cells and tagging of beta-actin with GFP.

Chimeric antigen receptor (CAR) T-cell therapy, first approved by the FDA in 2017, is a rapidly growing field in cancer therapy and involves the isolation and activation of T cells from a patient’s blood for ex vivo genetic modification. The engineered T cells are then infused back into the patient to enable T cell–mediated cytotoxicity as treatment. CRISPR-Cas9 is one of the most commonly leveraged nonviral editing tools for engineering T cells for therapeutic applications. Thermo Fisher now offers the Gibco CTS TrueCut Cas9 Protein for use as an ancillary material in cell and gene therapy applications.

This application note from Thermo Fisher Scientific assesses the performance of the CTS TrueCut Cas9 Protein against a research-grade Cas9 protein to confirm that the manufacturing scale-up of the enzyme had no significant impact on the product performance, indicating that the product can reliably be used for cell and gene therapy development.

Overcoming high dead volume to save precious and expensive reagents is an important goal for laboratories. The assumption that only pipetting from single tubes guarantees the lowest possible dead volume holds up well. However, even with automated single-channel pipettes, this is not an option when high throughput is required. Integra has developed novel divided reservoirs to reduce reagent wastage when using the Voyager adjustable tip spacing pipette.

This application note from Integra demonstrates how qPCR reagent transfer can be fully automated with high accuracy and low dead volume using an Assist Plus pipetting robot equipped with the Voyager adjustable tip spacing pipette and a novel dual reservoir adapter.

Multiomic single-cell studies are revolutionizing knowledge of the tumor immune microenvironment and are uniquely positioned to detect rare cell subsets that correlate in response to immunotherapy. DNA-barcoded antibody panels enable unambiguous classification of cell subsets via simultaneous measurement of surface proteins and the transcriptome. However, single-cell sequencing performs best on fresh samples while multicenter clinical trials routinely obtain frozen specimens.

In this on-demand webinar, Jasmine Chen, director of genomics at Abiosciences, shares Abiosciences’ effort in evaluating BioLegend’s TotalSeq-C Human Universal Cocktail using the 10x Genomics single-cell platform on fresh and frozen PBMCs. This includes bioinformatics pipelines to compare the quality control metrics, isotype-matched control performance, and cell subtype analyses. Advanced visualization and analysis tools were developed to interrogate the data in a flow cytometry paradigm, including complex gating strategies to identify rare cell subtypes. The pilot study is being expanded to larger-scale clinical settings and may help characterize important cell populations that are associated with disease status, pharmacodynamics, and therapeutic response.

Topics include:

• How multimodal single-cell genomics shows that fresh and frozen PBMC samples are largely concordant for transcriptome and cell-surface protein levels.
• How BioLegend’s bioinformatics approaches allowed rare cell subtype ID with sensitivity and selectivity rivaling flow cytometry.

This white paper from PINC AI discusses the causes of health inequities and how equity may be advanced through innovative and collaborative solutions that address the underlying systemic issues that contribute to inequities, and it describes a case study in which PINC AI collaborated with Henry Ford Health to develop solutions.

Mutations in BRCA1 and BRCA2 tumor-suppressor genes account for a significant portion of hereditary breast and ovarian cancer cases. Among them, large genomic rearrangements (LGRs) involving a loss or gain of partial complete BRCA exon(s) are responsible for up to 27 percent of all BRCA disease-causing mutations identified. However, these LGRs are frequently missed using both PCR-based methods and targeted NGS assays.

Given the difficulty in detecting LGRs, there is a need for a comprehensive BRCA1/2 testing algorithm including reference materials that incorporate pathogenic BRCA1/2 LGRs to support NGS assays that identify these mutations at both germline and somatic levels. Clinical studies have demonstrated that pathogenic BRCA1/2 mutations sensitized patients to platinum-based chemotherapy and PARP inhibitors. Current guidelines increasingly recommend BRCA testing in management and therapy selection. Accurate detection of BRCA1 or BRCA2 pathogenic variants is therefore critical in breast and ovarian cancer therapy as well as clinical management of disease including patients who are eligible for new PARP inhibitors.

This poster from LGC SeraCare describes the development and validation of reference material to support BRCA1 and BRCA2 gene testing, the first to include 10 LGRs, which will be useful in evaluating the ability to detect challenging LGRs and support PARP inhibitor treatment of patients with breast and ovarian cancers.

Clinical expectations for BCR-ABL monitoring have evolved over time both in response to more sensitive tests being developed and new treatments and management approaches emerging. Largely in response to these medical advances, many CML patients have been able to successfully manage their diseases over time, as evidenced by increasing long-term survival rates. Chronic management of an increasing population of CML patients, however, places unique pressure on supporting laboratories, requiring that testing become sensitive enough to support a broad spectrum of clinical decisions while also being scalable to accommodate an ever-increasing number of tests.

This on-demand webinar from Asuragen discusses how the CE-IVD-certified QuantideX qPCR BCR-ABL IS Kit can overcome challenges in CML monitoring, providing a simple, sensitive, and scalable approach to BCR-ABL monitoring that meets today’s clinical expectations for testing.

Hosted by Justin T. Brown, principal scientist of research and development at Asuragen, the webinar covers:

• How molecular monitoring fits within CML practice guidelines and how that continues to evolve and add incremental burden to laboratories.
• Key performance data for the QuantideX qPCR BCR-ABL IS kit and how it exceeds monitoring requirements while maintaining operational efficiency.
• Why CML management during the COVID-19 pandemic requires continued monitoring.

In this on-demand webinar from Asuragen, Dolors Colomer of the hematopathology section at Hospital Clinic Barcelona presents her perspective on the QuantideX qPCR BCR-ABL IS Kit as a simple, sensitive CE-IVD solution for BCR-ABL monitoring.