Jean-Philippe Laine

Copy number + SNV ! Combining these two data sources from embryo biopsies to get the most accurate PGT-A. This was definitely the main theme of this year's #PGDIS2024 presentations. Lots of groups are looking to do this with SNP array based PGTA (some great presentations), low pass NGS sequencing (tough to get good SNP data), amplicon based NGS (tough to get good CNV data). So it was great to see the #PTA PGTA data presented by Chris Weier The PTA based CNV+SNP (SNV) data just keeps on blowing us away with the ultra low noise CNV and the super high fidelity SNP data. MAPD <0.03 is normal and 150K SNP on a standard PGTA. It really is the best of both worlds for CNV and SNP reporting. Chris presented the example below from a PTA amped sample showing two 40% mosaic aneuploidies and - really for the first time - demonstrating PGT-A SNP based mosaic calling beautifully correlating with CNV mosaic calling. It's easy to spot by eye in the B-allele plot for chr7 and chr13, then to see it in the CNV plot. Although of course we do this calling automatically with #PGTai. Independently CNV and SNP calling mosaics and aneuploidies. It's the future of PGT-A. There is plenty more to come and the inventor of #PTA Charles Gawad #bioskryb hinted about the PTA future in a tour de force #PGDIS2024 presentation. Exciting times! #coopersurgical

112

3 Comments

"Q. How has the use of alternatives assessment in industry changed, how is it being used now, and what would help increase its uptake? A. It has grown, but it varies with different product sectors. Earlier on there was a lot more adoption within textiles and electronics. But now we’re talking to a much broader range of companies, and we’ve started to engage more with large retailers. For example, we’ve been working with Nike for a long time. We work with their innovation team so that they can screen all of their new materials, and that’s been a really great partnership. We’ve been able to go to the Nike offices a few times and provide trainings. They use our tools to look at their supply chain as well..." Ahead of next week's 28th Annual Green Chemistry & Engineering Conference, ACS Green Chemistry Institute interviews our Enhesa Sustainable Chemistry Director of Toxicology, Colleen McLoughlin, Ph.D.,DABT, E.R.T. on Advancing Alternatives Assessment Read the full Q&A >> https://lnkd.in/djBnuAcf

1

1 Comment

Members of the GRI Bio, Inc. management team discuss the encouraging preclinical data that was recently presented and #whatthismeans for its #IPF program and #SLE development programs. https://lnkd.in/eDa8WtjJ #NKT # IdiopathicPulmonaryFibrosis #SystemicLupusErythematosus

2

Happy Wednesday all! Check out this open access Cell Immunity review by Jason G. Cyster and Patrick C. Wilson, "Antibody modulation of B cell responses—Incorporating positive and negative feedback." Summary: Antibodies are powerful modulators of ongoing and future B cell responses. While the concept of antibody feedback has been appreciated for over a century, the topic has seen a surge in interest due to the evidence that the broadening of antibody responses to SARS-CoV-2 after a third mRNA vaccination is a consequence of antibody feedback. Moreover, the discovery that slow antigen delivery can lead to more robust humoral immunity has put a spotlight on the capacity for early antibodies to augment B cell responses. Here, we review the mechanisms whereby antibody feedback shapes B cell responses, integrating findings in humans and in mouse models. We consider the major influence of epitope masking and the diverse actions of complement and Fc receptors and provide a framework for conceptualizing the ways antigen-specific antibodies may influence B cell responses to any form of antigen, in conditions as diverse as infectious disease, autoimmunity, and cancer. #drugdiscovery #cancerresearch #antibodies #infectiousdisease #sarscov2 #autoimmunity #immunooncology #immunotherapy #scientificresearch

24

Happy Tuesday all! Check out this open access Immunological Review by Yu et al., "Single domain antibody: Development and application in biotechnology and biopharma." Summary: Heavy-chain antibodies (HCAbs) are a unique type of antibodies devoid of light chains, and comprised of two heavy chains-only that recognize their cognate antigen by virtue of a single variable domain also referred to as VHH, single domain antibody (sdAb), or nanobody (Nb). These functional HCAbs, serendipitous discovered about three decades ago, are exclusively found in camelids, comprising dromedaries, camels, llamas, and vicugnas. Nanobodies have become an essential tool in biomedical research and medicine, both in diagnostics and therapeutics due to their beneficial properties: small size, high stability, strong antigen-binding affinity, low immunogenicity, low production cost, and straightforward engineering into more potent affinity reagents. The occurrence of HCAbs in camelids remains intriguing. It is believed to be an evolutionary adaptation, equipping camelids with a robust adaptive immune defense suitable to respond to the pressure from a pathogenic invasion necessitating a more profound antigen recognition and neutralization. This evolutionary innovation led to a simplified HCAb structure, possibly supported by genetic mutations and drift, allowing adaptive mutation and diversification in the heavy chain variable gene and constant gene regions. Beyond understanding their origins, the application of nanobodies has significantly advanced over the past 30 years. Alongside expanding laboratory research, there has been a rapid increase in patent application for nanobodies. The introduction of commercial nanobody drugs such as Cablivi, Nanozora, Envafolimab, and Carvykti has boosted confidence among in their potential. This review explores the evolutionary history of HCAbs, their ontogeny, and applications in biotechnology and pharmaceuticals, focusing on approved and ongoing medical research pipelines. #drugdiscovery #nanobodies #cancerresearch #therapeutics #immunology #antibodies #scientificresearch

27

1 Comment

Happy Friday all! Check out this open access Nature Scientific Reports article by Abali et al., "A nanowell platform to identify, sort and expand high antibody-producing cells." https://lnkd.in/gMuJNSxf Abstract: Increased use of therapeutic monoclonal antibodies and the relatively high manufacturing costs fuel the need for more efficient production methods. Here we introduce a novel, fast, robust, and safe isolation platform for screening and isolating antibody-producing cell lines using a nanowell chip and an innovative single-cell isolation method. An anti-Her2 antibody producing CHO cell pool was used as a model. The platform; (1) Assures the single-cell origin of the production clone, (2) Detects the antibody production of individual cells and (3) Isolates and expands the individual cells based on their antibody production. Using the nanowell platform we demonstrated an 1.8–4.5 increase in anti-Her2 production by CHO cells that were screened and isolated with the nanowell platform compared to CHO cells that were not screened. This increase was also shown in Fed-Batch cultures where selected high production clones showed titers of 19–100 mg/L on harvest day, while the low producer cells did not show any detectable anti-Her2 IgG production. The screening of thousands of single cells is performed under sterile conditions and the individual cells were cultured in buffers and reagents without animal components. The time required from seeding a single cell and measuring the antibody production to fully expanded clones with increased Her-2 production was 4–6 weeks. #drugdiscovery #antibodies #cancerresearch #immunotherapy #immunooncology #scientificresearch

11

Lake N. Paul, PhD. is in San Diego at the Biotechnology Innovation Organization #BIO2024 conference meeting with colleagues & future clients. Connect with him in person to learn about how, as a Collaborative Research Organization, we are best positioned to support your analytical program. #aav #genetherapy #rarediseases #biophysics #STEM #STEMPhilly #biochemistry #celltherapy #bioanalysisllc #PhillyBusiness #phillyscience

9

Happy Thursday all! Check out this open access Nature Leukemia review by Lei et al., "Leveraging CRISPR gene editing technology to optimize the efficacy, safety and accessibility of CAR T-cell therapy." https://lnkd.in/gAWFHq-j. Abstract: Chimeric Antigen Receptor (CAR)-T-cell therapy has revolutionized cancer immune therapy. However, challenges remain including increasing efficacy, reducing adverse events and increasing accessibility. Use of Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR) technology can effectively perform various functions such as precise integration, multi-gene editing, and genome-wide functional regulation. Additionally, CRISPR screening using large-scale guide RNA (gRNA) genetic perturbation provides an unbiased approach to understanding mechanisms underlying anti-cancer efficacy of CAR T-cells. Several emerging CRISPR tools with high specificity, controllability and efficiency are useful to modify CAR T-cells and identify new targets. In this review we summarize potential uses of the CRISPR system to improve results of CAR T-cells therapy including optimizing efficacy and safety and, developing universal CAR T-cells. We discuss challenges facing CRISPR gene editing and propose solutions highlighting future research directions in CAR T-cell therapy. #drugdiscovery #cancerresearch #crispr #tcelltherapy #immunooncology #immunotherapy #scientificresearch

37

1 Comment

Exciting news as we just released a TSLP Responsive Luciferase Reporter Ba/F3 Cell Line #82500 to support preclinical autoimmune drug discovery research: https://lnkd.in/gvKjW7R5 Summary: Thymic stromal lymphopoietin (TSLP) is a protein that functions as a type I cytokine, as an alarmin, and as a growth factor in the immune system. It is involved in type 2 immune responses, T helper type 2 responses, and in the maturation and recruitment of dendritic cells (DCs), T cells, B cells, neutrophils, mast cells, and other lymphoid cells. Its expression can be induced by infections, pro-inflammatory cytokines, proteases, and mechanical injury. TSLP is linked to allergic reactions such as asthma, atopic dermatitis, and food allergies, by inducing the expression of OX40L, CD80 and CD86, and stimulating CD4+ T cells. TSLP signals through a heterodimeric receptor of TSLP-R (CRLF2) and IL7Ra (CD127) to activate JAK2/STAT5 signaling. In 2021, the TLSP-neutralizing antibody tezepelumab was approved for the treatment of severe asthma. TSLP is an active target for investigation in ongoing clinical trials for the treatment of autoimmune disorders, and this TSLP Responsive Luciferase Reporter Ba/F3 Cell Line is a murine cell line engineered to express both TSLP-R and IL-7Ra that reports on TSLP activation via STAT5 Luciferase, making it an excellent tool for TSLP drug discovery research. Reach out to me here or by email ([email protected]) with any questions or for a quote! #drugdiscovery #immunology #autoimmune #immunotherapy #scientificresearch

16

More improvements on the way... one solution for Illumina TSO500 + HRD, faster turnaround times and more..

18

CRS3123 is a small molecule protein synthesis inhibitor that acts on the novel target methionyl-tRNA synthetase (MetRS). CRS3123 has numerous potential advantages over current CDI therapies. Learn more about C. difficile Infection (CDI) and the Phase 2 study of CRS3123 here: https://bit.ly/3zhg5Kb

11

CRS3123 is a small molecule protein synthesis inhibitor that acts on the novel target methionyl-tRNA synthetase (MetRS). CRS3123 has numerous potential advantages over current CDI therapies. Learn more about C. difficile Infection (CDI) and the Phase 2 study of CRS3123 here: https://bit.ly/3zhg5Kb

3

Do you know when companion diagnostics (CDx) are needed for your cell and gene therapy programs? Or what kind of testing is required and how to choose the right lab partner for a CDx assay? In our blog, you’ll learn from Labcorp subject matter experts as they answer key questions you may have about developing CDx for your cell and gene therapy programs. Learn more: https://lnkd.in/gSChJieM #CellandGeneTherapy #CompanionDiagnostics

4

OMAPiX Announces Strategic Partnership with Parse Biosciences to Offer Single-Cell Sequencing Products Across Therapeutic Areas and Indications Frederick, Maryland – OMAPiX, a leader in spatial multiomics custom data and analytics solutions, today announced a strategic partnership with Parse Biosciences, a pioneer in scalable single-cell sequencing technology. Through this collaboration, OMAPiX is now a Certified Service Provider (CSP) offering Parse Biosciences' innovative single-cell sequencing products, which utilize a proprietary fixation and permeabilization method, combined with combinatorial barcoding, to generate high throughput and high-quality single cell data sets. OMAPiX offers a diverse portfolio of platforms, including high-throughput in situ sequencing, single-cell and spatial transcriptomics, spatial profiling, and image analysis. These solutions are designed to help pharmaceutical, academic, and biotechnology research organizations gain a deeper understanding of cellular function and disease mechanisms. “While traditionally seen as a spatial biology lab, the new OMAPiX is designed to support an array of research approaches. Our passion, to bring precision medicine to patients, can only truly propel forward if we enable access to the advances the OMICs field has seen in recent years. As such, it has been exciting to bring in new product offerings, such as Parse Biosciences, to support a range of applications,” said Linda Orzolek, the new head of lab operations at OMAPiX. The company’s newly expanded, state-of-the-art laboratory in Frederick, MD, is equipped with cutting-edge technologies to analyze the genome, transcriptome and proteome at unmatched resolution, opening the doors for both novel discoveries and clinical validations. OMAPiX’s deep expertise in spatial biology and molecular profiling enables the company to provide tailored solutions for clients across various stages of drug discovery and development. The company is rapidly scaling its capabilities in both sample processing and data analytics to meet the growing demand for spatial and multiomics solutions. “We are thrilled to partner with OMAPiX and add them to our network of certified service providers,” said Alex Rosenberg, CEO and co-founder of Parse Biosciences. “Their expertise and commitment to excellence make them an invaluable partner in providing the research community with scalable and high-quality single cell solutions.” This partnership strengthens OMAPiX's position as a comprehensive solution for research and clinical applications, covering gene expression analysis, protein localization, cell interactions, and tissue-level profiling. To read the full press release https://lnkd.in/gm9Pq8Ju

47

2 Comments

Axol Bioscience Secures SMART Grant to Accelerate the Development of a Commercial iPSC-Powered ALS Models - https://lnkd.in/ghTe_uFr Axol Bioscience has been awarded a SMART Grant by Scottish Enterprise to Accelerate ALS Research through the development of ALS-related phenotypes using human iPSCs. This represents another significant step towards better disease modelling and ALS drug discovery. The key objectives of this project are to: -Develop a quality manufacturing system for iPSC-derived ALS relevant cell types - Characterise and validate the cells using ALS relevant end points; TDP43 aggregation, Neurofilament Light elevation and Cryptic Exon Sequencing - Develop and characterise an ALS co-culture model which includes motor neurons, microglia and astrocytes - Commercialise an easy-to-use model system to drive forward ALS drug discovery Axol Bioscience Ltd., who is a world leaders in human induced pluripotent stem cell (iPSC) manufacturing, consistently and at scale, has been awarded a SMART Grant by Scottish Enterprise. This significant milestone is a testament to its commitment to advancing cutting-edge research and innovation in the iPSC space. #ipscells #stemcells #ALS #drugdiscovery #reserach Duncan Borthwick PhD Teodora Popovici

30

2 Comments

Happy Friday all! Check out this open access Mol Therapy Oncology article by Schoenfeld et al., "T cell receptor-directed antibody-drug conjugates for the treatment of T cell-derived cancers." Summary: T cell-derived cancers are hallmarked by heterogeneity, aggressiveness, and poor clinical outcomes. Available targeted therapies are severely limited due to a lack of target antigens that allow discrimination of malignant from healthy T cells. Here, we report a novel approach for the treatment of T cell diseases based on targeting the clonally rearranged T cell receptor displayed by the cancerous T cell population. As a proof of concept, we identified an antibody with unique specificity toward a distinct T cell receptor (TCR) and developed antibody-drug conjugates, precisely recognizing and eliminating target T cells while preserving overall T cell repertoire integrity and cellular immunity. Our anti-TCR antibody-drug conjugates demonstrated effective receptor-mediated cell internalization, associated with induction of cancer cell death with strong signs of apoptosis. Furthermore, cell proliferation-inhibiting bystander effects observed on target-negative cells may contribute to the molecules’ anti-tumor properties precluding potential tumor escape mechanisms. To our knowledge, this represents the first anti-TCR antibody-drug conjugate designed as custom-tailored immunotherapy for T cell-driven pathologies. #drugdiscovery #cancerresearch #immunotherapy #immunooncology #tcelltherapy #tcr #adc #scientificresearch

24

Xenetic Biosciences, Inc. Extends Research Agreement with the University of Virginia for the Advancement of its DNase-Based Oncology Platform https://bit.ly/4gDqqCw #Oncology #SolidTumors #DNase

1

On January 8, 2025, Avidity Biosciences, Inc. announced its progress and planning for a transformational year in 2025. #DuchenneNews Major anticipated milestones include executing on three potentially registrational programs, filing a Biologics License Application for delpacibart zotadirsen (del-zota) for people living with Duchenne mutations amenable to exon 44 skipping (DMD44), preparing for multiple product launches in DMD44, myotonic dystrophy type 1 (DM1) and facioscapulohumeral muscular dystrophy (FSHD) and building a global, fully integrated company to support a growing AOC pipeline in neuromuscular diseases and precision cardiology. Full press release: https://bit.ly/40hG1RF

5