Panelists:

Erin Dieveney

Vice President, Quality Assurance
Aldevron

View Bio

Panelist

Erin Dieveney

Erin Dieveney leads quality assurance at Aldevron where she helps ensure the quality, compliance, and reliability of products that enable next-generation genomic medicines. Throughout her career, Erin has assumed increasing leadership responsibilities across quality, regulatory affairs, product development, and customer support, developing deep expertise in bringing innovative life sciences technologies to market.

Close

Khaled Yamout

Founder & CEO
Y-Chem Consulting

View Bio

Panelist

Khaled Yamout

Khaled Yamout is a thought leader in analytical sciences, quality and manufacturing. He was previously senior director of analytical services and quality control at TriLink Biotechnologies, where he oversaw the Analytical Sciences Center of Excellence and all analytical aspects of method development and validation to product release and stability, in support of regulatory filings for both small and large molecules. Prior to TriLink, Khaled held various positions in quality control, R&D, and manufacturing where he supported several drug products (small molecules and biologics) from clinical phase to commercial. His experience spans Fortune 500 firms as well as small entrepreneurial businesses in the areas of synthetic, analytical, colloidal, surface modification, protein, and antibody modification and purification.

Khaled holds a BS degree in chemistry from the University of Texas at Arlington.

Close

Kok-Seong Lim, PhD

Founder and Principal
Eight Crest Strategies

View Bio

Panelist

Kok-Seong Lim, PhD

Kok-Seong Lim, PhD, is a pharmaceutical leader with more than 20 years of experience in biological research and development, specializing in analytical sciences, quality control, and CMC strategy for advanced therapy platforms. He has held multiple management roles at Metagenomi, Aura Biosciences, Editas Medicine, and Thermo Fisher Scientific (formerly Brammer Bio), where he contributed to the advancement of more than ten gene therapies and CRISPR-based medicines for rare diseases and oncology indications.

Throughout his career, Kok-Seong has led the buildout of GMP-compliant facilities and analytical infrastructures to support early- and late-stage development. He has managed complex, multimillion-dollar budgets and contributed to regulatory submissions in both the U.S. and EU. Kok-Seong has served on committees such as the USP Biologics Expert Committee for Cell and Gene Therapy and the Standards Coordinating Body, helping to shape best practices and standards for the cell and gene therapy community.

Kok-Seong earned his PhD in biochemistry from the National University of Singapore and holds a BSc in pharmacy from the University of Strathclyde, Scotland.

Close

Michael Lehmicke

Senior Vice President, Scientific Affairs
Alliance for Regenerative Medicine

View Bio

Panelist

Michael Lehmicke

Michael Lehmicke joined the Alliance for Regenerative Medicine in 2019 as its first director of science and industry affairs. Michael has over 20 years of R&D experience in biomaterials, medical devices, and regenerative medicine. He has led product development teams for class II devices, human cell and tissue-based products, and drug/device combination products. He is a creator and an inventor with multiple U.S. patents to his name.

Michael has an MSc in biomedical engineering, with a focus on tissue engineering, from Drexel University. Michael’s areas of expertise include cell-based tissue engineering, bioceramics, biodegradable polymers, project management, strategic pipeline development, and business development.

Close

As biologics become more diverse, complex, and faster-moving, how can the biotech and biopharma industry ensure that quality standards keep pace with innovation? We will address this fundamental question in the latest GEN Spotlight on Biologics Standards for Innovation, Quality and Access, presented in partnership with USP. This virtual event will explore how evolving standards can provide a stronger foundation for developing and manufacturing next-generation therapeutics.

This Spotlight on Biologics Standards for Innovation, Quality and Access brings together experts from across biopharma, standards development, and analytical science to examine the challenges of testing increasingly complex modalities, including monoclonal antibodies, cell and gene therapies, and RNA therapeutics. Sessions will explore when and how to standardize emerging therapies, a practical layered framework for quality—from raw materials and analytical methods to identity, purity, and potency—and the growing importance of community input in developing standards for new modalities.

Session highlights include:

• A roundtable explores layered frameworks to ensure quality in multi-modal therapeutic development featuring Erin Dieveney (Aldevron) and Kok-Seong Lim, PhD (Eight Crest Strategies).
• A panel discussion on building standards for a multi-therapeutic modality future, featuring Khaled Yamout (Y-Chem Consulting) and Michael Lehmicke(Alliance for Regenerative Medicine)
• And a discussion featuring senior executives from USP on the importance of community input in developing standards for new modalities.

Join us on Wednesday, October 14, to discover how standardization can reduce development risk, support innovation, and help establish a shared foundation for the future of biologics.

Registration for this 2.5-hour event is free.

Produced with support from:

The post Biologics Standards for Innovation, Quality and Access appeared first on GEN - Genetic Engineering and Biotechnology News.

The drug, Aqneursa^® (levacetylleucine), was approved by the FDA in September 2024 for neurological manifestations of Niemann-Pick disease Type C (NPC) in adults and children weighing 15 kg (33 pounds) or more,  and by the European Medicines Agency (EMA) in January.

On September 18, the FDA approved a supplemental New Drug Application expanding the label of Aqneursa to become the first and to date only drug approved for the treatment of ataxia in ataxia-telangiectasia (A-T) patients weighing 15 kg (33 pounds) or more. Aqneursa is now under review by the EMA for adults and children diagnosed with A-T.

“The planned acquisition of IntraBio actively demonstrates Shionogi’s solid commitment to building a leading global rare disease business,” Isao Teshirogi, PhD, Shionogi’s president, CEO, and representative director said Monday in a statement. “Bringing Aqneursa to Shionogi after our acquisition of Radicava^® will deepen our commitment to rare disease communities, expand our capabilities and strengthen our portfolio as we advance future innovation for patients with significant unmet needs.”

Investors initially appeared less enthusiastic about the IntraBio acquisition, as Shionogi’s shares traded on the Tokyo Stock Exchange fell about 4.5% Monday, from ¥2,786 ($17.61) to ¥2,661 ($16.82)—but the stock bounced back Tuesday, all but recovering with a 3.8% gain that sent shares up to Y2,763 ($17.47).

However, Sumant Kulkarni, a senior analyst covering biotechnology with Canaccord Genuity, viewed the deal more positively.

“In summary, this transaction underscores our view that companies with approved products for rare indications, neuro or otherwise, present significant scarcity value for strategics and investors alike,” Kulkarni wrote Monday in a research note. “We are not entirely surprised by this development, but are encouraged by the upfront consideration.”

Kulkarni added: “In fact, we were surprised that IntraBio had remained independent for the time it did, but the timing makes sense given the recent approval for A-T, which adds another leg to its story.”

‘Plenty of financial firepower’

The acquisition of IntraBio comes two months after Teshirogi told Bloomberg News in an interview that Shionogi was “actively pursuing” at least three acquisition opportunities: “From a cash flow perspective, we’ve become a company with plenty of financial firepower. If a good opportunity comes along, there’s absolutely no reason for us to hesitate over any M&A.”

Teshirogi also said Shionogi was looking to expand its U.S. and European manufacturing capacity in order to diversify its production base beyond Japan and thus reduce geopolitical risk over the next decade.

To that end, Shionogi pursued and won a U.S. government contract in April to establish a Stateside drug product manufacturing site for its Fetroja^® cefiderocol), a cephalosporin antibacterial indicated to treat adults with complicated urinary tract infections (cUTI) including pyelonephritis; as well as hospital-acquired and ventilator-associated bacterial pneumonia (HABP/VABP).

The contract—awarded through the Biomedical Advanced Research and Development Authority’s (BARDA) Project BioShield—was initially funded at $119 million with multiyear options for a total of up to $482 million.

Shionogi signaled its intent to focus on rare disease drugs in April when it agreed to acquire Radicava (edaravone), a small molecule treatment for amyotrophic lateral sclerosis (ALS), from Tanabe Pharma for $2.5 billion and a potential royalty on future sales. At the time, Shionogi said the deal would benefit it by adding approximately $700 million in annual global sales during the company’s current 2026 fiscal year, which began on April 1.

59% leap

That would represent a 59% leap from Shionogi’s entire FY 2025 earnings before interest taxes, depreciation, and amortization (EBITDA) of ¥187.72 billion ($1.187 billion), up 4.7% from ¥179.296 billion ($1.134 billion) in FY 2024.

Radicava generated ¥94.491 billion ($597.582 million) in the 2025 fiscal year that ended on March 31 of this year.

“Through this acquisition, the Company aims to strengthen its business foundation and enhance its corporate value over the medium to long term by maximizing the value of edaravone and expanding its provision of solutions in the rare disease area,” Shionogi explained in reporting fiscal Q1 (April-June) 2026 results in August.

Radicava is marketed under that name as an intravenous (IV) infusion, and as an oral suspension called Radicava ORS. The IV version was approved by the FDA in 2022 and the oral suspension version, two years later.

Based in Austin, TX, IntraBio was established in 2015 to discover, develop, and commercialize therapies for neurodegenerative diseases with high unmet medical need, by commercializing research generated by its scientific co-founders—Professors Grant Churchill, PhD, Antony Gallone, PhD, and Frances Platt, PhD, all of the University of Oxford; and Michael Strupp, MD, of the University of Munich.

Privately held IntraBio finished last year with a $35.8 million net loss on net sales of $67.867 million—all of it generated from sales of Aqneursa—according to data disclosed by Shionogi in its announcement of the acquisition.

Shionogi is expected to close on its acquisition of IntraBio during this quarter, subject to customary closing conditions.

The post Shionogi Grows Rare Disease Portfolio with $2B IntraBio Acquisition appeared first on GEN - Genetic Engineering and Biotechnology News.

Today, despite the astounding breakthroughs of the past quarter-century, positive responses to advanced therapies such as checkpoint inhibitors and cell and gene therapies are still limited to a relatively small subset of patients. To improve efficacy and understand patient response, Stengel says, “We need to consider all layers of epigenetic regulation to better understand gene regulation and build better models of biology, especially right now, with AI enabling the integration of huge amounts of data.”

Despite the increasing influx of information, “We still have gaps in our understanding of how information flows from DNA to proteins and ultimately phenotype,” Stengel says. In a multiomics environment, RNA modifications—which she calls “an essential layer of that multiomic stack”—have received relatively little attention because they are considered particularly hard to measure accurately.

To help resolve that issue, AlidaBio is focusing on three of the most important RNA modifications as a way to create better and more useful epitranscriptomics models to improve scientists’ understanding of the many layers of epigenetic regulation.

Why epitranscriptomics

“Epitranscriptomics are a readout of the cell state,” Stengel says. “Single-cell transcriptomics and spatial transcriptomics have shown a huge amount of heterogeneity—similar cell types are characterized by different RNA expression patterns that define what a cell is doing at a given time.” As an example of the timescales of response, she says, “To reset DNA methylation can take up to two weeks. To reset an RNA expression pattern can take a day, and RNA modifications can change RNA expression within a few hours.” Understanding those patterns and their time to action can significantly affect a cell’s response to therapeutics.

“RNA modifications don’t change the genetic code, but they change what RNA does,” Stengel emphasizes. “N6-methyladenosine (m6A), the most important mRNA modification, can quickly mark RNA transcripts associated with a previous cell state for degradation and, at the same time, promote the translation of genes that are associated with the future cell state. It is also involved in alternative splicing regulation, which creates more protein diversity.”

Epitranscriptomics method development has gained significant momentum in recent years. Current nanopore-based direct RNA sequencing can detect a subset of modifications in native, long RNA molecules. However, the approach currently requires relatively large quantities of high-quality full-length RNA.

Short-read, one-pot detection

Alida Biosciences expanded the industry’s capabilities in 2025 by launching its EpiPlex platform. It was the first commercial solution to analyze sparse and highly-degraded RNA often found in clinical samples and provide simultaneous, one-pot detection, localization, and quantification of three of the best-studied and most frequently occurring mRNA modifications: N6-methyladenosine (m6A), inosine, and pseudouridine, along with gene expression. The company offers kits, analysis software, and services.

“To develop clinical and translational applications, you need to look at clinical samples (fresh-frozen or formalin-fixed paraffin-embedded tissues, and liquid biopsies, for example) that are present at low quantities or that may be highly degraded,” she explains.

The long list of potential applications includes patient stratification for specific therapies and response monitoring, as well as therapeutic development of cancer drugs and measuring immune cell fitness. “m6A, the most common modification, plays a huge role in cell differentiation and cell fate,” Stengel says.

Entrepreneurial leanings

Stengel formed the company five years ago, leaving a safe corporate position on the belief that she could create a company that would fill a key knowledge gap.

“I had spent a significant number of years in large companies—including Illumina—developing genomics technologies,” she says. Researchers at such companies, however, tend to be involved in either the inception or the development of a product. “I wanted to see things through from the beginning to the end. I thought a smaller company would be the ideal environment to do exactly that. I resigned my job and started putting the pieces together.

“When I started the company, many [in the industry] had never heard of epitranscriptomics,” she says. Nonetheless, she secured venture capital funding within six months and built a small, core team.

Those early days found her in the lab, working with just a few scientists. “Getting the first, preliminary data was so exhilarating!” she recalls. “It’s a good day when everything works in the lab.”

Epitranscriptomics is emerging from a niche discipline, so now most conference attendees, “regardless of the conference,” Stengel adds, are aware of the field. Although, she admits, “not everybody knows why they are important. Yet, that’s a huge step forward.”

Commercial vision

As scientists increasingly recognize the role RNA modifications play in therapeutic development and outcomes, she can focus on scaling the company and its commercial capabilities. “We started out very R&D heavy,” and now are beginning to earn revenue to fund further innovations. Potential clients include multiomics companies, research hospitals, and “to some extent, diagnostics,” she says.

Currently, AlidaBio is working with the oncology company STORM Therapeutics to understand the mechanism of action and to stratify patients for a Phase II drug that acts on methyltransferase-like 3 (Mettl3), the m6A writer enzyme. This is one of a few areas in which RNA modification can make breakthroughs in patient treatment and stratification, she says. “We’re also very interested in predicting response to PD-L1 inhibitors.”

For AlidaBio, bioinformatics is an area of continual focus, along with making analysis output more interactive. “We also are applying machine learning models to integrate the amount of information between RNA modifications and gene expression, so there will be significant updates to the EpiScout^® analysis software,” Stengel says. Other plans remain confidential.

For both the company and the industry, “I think the next inflection point is when epitranscriptomics becomes part of mainstream multiomics,” Stengel says. When that happens, researchers will consider RNA expression data incomplete without information about RNA modification.

Therefore, eventually, “RNA modifications will become another standard layer that’s integrated into AI models of biology,” she continues. “The real test will be demonstrating that this layer improves patient stratification, predicts treatment response, or identifies new therapeutic opportunities. Once that happens, I think the field will move from being scientifically interesting to clinically indispensable.”

The post The Epitranscriptome Heads Toward Clinical Necessity appeared first on GEN - Genetic Engineering and Biotechnology News.

As genomic research tackles increasingly complex biological questions, researchers need tools capable of looking beyond the most readily resolved regions of the genome. Repetitive sequences, structural variation, and other complex genomic features can be challenging to resolve with many conventional sequencing workflows. At the same time, laboratories must balance accuracy and speed with practical considerations, including read length, throughput, batch size, and access to data.

Sequencing by expansion (SBX), the technology underlying Roche’s AXELIOS 1 platform, takes a different approach to these challenges by physically expanding the space between encoded bases before detection.

Creating space for a clearer signal

SBX leverages a specialized polymerase that converts the sequence of a target DNA or RNA molecule into a measurable surrogate polymer called an Xpandomer, using nucleotide analogs. The resulting Xpandomer is approximately 50 times longer than the original molecule, creating greater physical separation between encoded bases.

The Xpandomer is then measured as it passes through a reusable complementary metal-oxide semiconductor (CMOS) sensor containing millions of nanopores. Its high signal-to-noise reporters are designed to support accurate, ultra-rapid single-molecule sequencing with near real-time base calling and analysis. This architecture may help researchers investigate a range of genomic features, including single nucleotide variants, insertions and deletions, copy-number alterations, repetitive sequences and other complex structures.

Flexibility beyond chemistry

The utility of a sequencing technology depends on more than chemistry alone. Research needs can vary substantially from one project to another and even within the same laboratory. AXELIOS 1 pairs SBX chemistry with a sequencing architecture designed to accommodate that variability. The system offers configurable batch sizes, allowing researchers to run smaller batches without waiting to accumulate enough samples for a larger run.

Researchers can also adjust read length according to experimental needs, with reads up to approximately 1,500 base pairs (with a distribution from ~200bp to ~1500 bp) under appropriate sample and library preparation conditions. The platform is capable of end-to-end, same-day whole genome sequencing (WGS) in research workflows, while near real-time base calling and analysis enable access to data as a run progresses.

This flexibility extends across multiple research applications. SBX has been tested in proof-of-principle studies for WGS, RNA sequencing (RNA-seq), single-cell RNA sequencing (scRNA-seq), spatial analysis, and methylation studies. For each application, the AXELIOS 1 Platform sequences Xpandomer molecules that were created from libraries made with the AXELIOS 1 DNA Library Prep Kit. The data is then analyzed using the no-cost, open-source XOOS bioinformatics analysis suite tailored for SBX. Collaborations also support applications and tools across the sequencing ecosystem, including support for SBX through Google DeepVariant.

Broadening the genomic picture

Modern genomics rarely relies on a single experimental approach. Researchers may need to examine genomic variation, gene expression, cellular heterogeneity, or epigenetic changes to build a more complete biological picture. Sequencing platforms that accommodate different applications and project sizes can allow laboratories to design workflows around the scientific question rather than instrument constraints.

By combining a new approach to sequencing chemistry with flexible read lengths, batch sizes, and research applications, AXELIOS 1 is designed to expand the range of genomic questions researchers can pursue. As sequencing continues to evolve, these capabilities could help scientists interrogate previously challenging regions of the genome and build a more complete foundation for biological discovery.

For Research Use Only. Not for use in diagnostic procedures. AXELIOS is a trademark of Roche.

To learn more, visit go.roche.com/AXELIOS1article

The post Expanding the Possibilities of Next-Generation Sequencing appeared first on GEN - Genetic Engineering and Biotechnology News.

Introduction

Prions are infectious proteins that cause neurodegenerative diseases in animals including bovine spongiform encephalopathy (cattle), Creutzfeldt-Jakob disease (humans), and chronic wasting disease (deer, elk and other cervids).¹ Prion diseases, also known as transmissible spongiform encephalopathies, result from misfolded proteins that accumulate primarily in the cells of the nervous system including the brains of infected animals. More widely, protein misfolding is linked to diverse neurological and non-neurological diseases and further research is needed in many areas due to the central importance of protein folding and aggregation in biology.

Prions propagate after regularly folded prion proteins (PrP^C) are converted into misfolded, aggregation-prone PrP^Sc proteins that build up and yield amyloids. These misfolded proteins and their aggregates damage nerve and other cells and, over time, lead to a decline in brain function and ultimately death.  With no cure available for prion diseases, researchers are striving to improve assay sensitivity and exploit the benefits of real-time monitoring to support the development of better diagnostic and treatment approaches.

RT-QuIC assays and microplate readers for prion analysis

Prions typically replicate by a series of sequential, amplifying events. Misfolded PrP^Sc acts as a point of recruitment of normal PrP^C cellular prion proteins. This interaction converts the recruited normal protein into the abnormal conformation setting in place a chain reaction where the protein-protein aggregates grow to produce a larger seed of misfolded proteins. As the aggregates grow, they can fragment to produce new nucleation sites. The seeds are eventually transformed into fibers of amyloid-rich assemblies that comprise significant amounts of beta-sheet conformations of the misfolded proteins.

The most widely used assay for detecting misfolded prions in biological samples is the RT-QuIC (Real-time quaking-induced conversion) assay. RT-QuIC assays are highly sensitive, seeding amplification assays that detect disease-associated prion activity. Formation of amyloid proteins is measured in real time using the fluorescent dye thioflavin T (ThT) whose emission increases significantly upon binding to beta-sheet-rich amyloid structures. Other dyes such as Congo Red are available that bind to amyloid but show reduced specificity for fibril proteins. Cyclic shaking accelerates fragmentation of the growing fibrils and produces a rapid amplification of the original prion seed. In practice, RT-QuIC assays generate characteristic amplification curves (figure 1) that comprise a baseline phase, an exponential increase in fluorescence, and a plateau phase. The lag time, maximum fluorescence, and reaction kinetics can provide quantitative or semi-quantitative measurements of prion seeding activity.

In the experiments shown in figure 1, scrapie brain homogenates were harvested 10 days after inoculation, incubated over time with shaking for the specified serial dilutions of Syrian hamster 263K cells, and ThT fluorescence was measured. The assays were quantified by measuring the loss of seeding activity at the end-point dilution.

Microplate readers and detection technologies for the investigation of amyloid

Microplate readers offer a robust platform for performing prion assays and measuring protein misfolding and aggregation. The ability to combine sensitive, high-performance kinetic fluorescence measurements with periodic cycles of rigorous shaking and consistent temperature control makes them the most widely adopted and practicable system for effective RT-QuIC assays.

Originally, the RT-QuIC assay was developed on the FLUOstar^® Omega microplate reader from BMG LABTECH which quickly became an international standard for prion analysis. BMG LABTECH readers, which continue to lead the way for prion detection and activity measurements, offer a robust platform for shaking for extended periods of time (over multiple days), while periodically reading the fluorescent signal as ThT is incorporated into amyloid aggregates.

Applications for protein misfolding

As mentioned earlier, protein misfolding has impact beyond prion disease and is a hallmark of impaired function in a wide range of conditions including Alzheimer’s disease, Parkinson’s disease, Huntington’s disease and amyotrophic lateral sclerosis. The way certain proteins misfold and aggregate is closely tied to how proteins become toxic and cause neurodegenerative diseases.

BMG LABTECH´s application note “Monitoring amyloid-beta aggregation in real-time using a FLUOstar Omega microplate reader²” provides one example where the accumulation of misfolded amyloid protein aggregates linked to Alzheimer’s disease is measured using ThT. Figure 2 shows some signal curves for samples and controls where ThT incorporation into newly formed amyloid-beta fibrils is measured.

In figure 2, error bars represent the deviation of replicate wells within one plate from the mean. All signal curves show a clear increase in fluorescence with time. This increase illustrates the incorporation of ThT into the newly formed amyloid-beta fibrils. After some time, a plateau is reached that is considered as the endpoint of amyloid formation and ThT incorporation process.

Protein misfolding and aggregation are likely to play a critical role in many processes related to aging. Misfolded proteins are also thought to influence different aspects of metabolic dysfunction and amyloid accumulation although the mechanism for most of these effects remains poorly understood. ThT assays thus offer applications across multiple disease areas and research domains.

Future developments

RT-QuIC assays have significantly accelerated research and analysis into prions compared with earlier more costly and lengthy bioassays where infected animals were studied over months. RT-QuIC assays also offer potential for disease surveillance in populations of prion-infected animals in the wild that could impact public health. Researchers are also looking at ways to use RT-QuIC-based screening assays to ensure the safety of human food chains. In this context, microplate readers and RT-QuIC assays have been used in experimental settings to characterize prion-seeding activity in samples of tissue from wild and farmed deer that may have been exposed to chronic wasting disease.³

Beyond surveillance, new drugs are actively being sought for different targets related to protein folding and amyloid accumulation. In clinical trials, translatable biomarkers are needed that track the progression and severity of the neurodegenerative diseases impacted by protein misfolding and aggregation. Progress in artificial intelligence and modeling techniques will enhance studies of protein folding and misfolding which should bring further advances to the drug discovery space.

Demand for ThT assays is poised to increase due to the lack of interventions for neurological and non-neurological diseases caused by protein misfolding and aggregation events and the potential for other high-impact applications.

ThT-related assays are therefore moving away from being a means for a rapid diagnosis towards offering a quantitative tool for disease surveillance, pathogenesis, and therapeutic development across a wide range of disease and fundamental research areas in the life sciences.

BMG LABTECH offers a portfolio of single- to multimode microplate readers ideally suited for studying protein misfolding and aggregation. While the FLUOstar Omega remains the gold standard for RT-QuIC and seeding assays, the PHERAstar^® FSX was specifically conceived for screening campaigns and is the go-to reader for high-performance high-throughput screening. Both the VANTAstar^® and CLARIOstar^® Plus allow for wavelength flexibility and include Enhanced Dynamic Range technology for superior performance and ease of use. Collectively, these multimode readers combine high performance with miniaturized assays and short measurement times, delivering considerable savings on materials and other resources.

References

1. Dong TT, Satoh K. The Latest Research on RT-QuIC Assays-A Literature Review. Pathogens. 2021 Mar 5;10(3):305. doi: 10.3390/pathogens10030305.
2. Baumann F. Following Abeta Fibrillization/Aggregation in Real-Time | BMG Labtech. n.d. [Last accessed: 9/14/2026].
3. Li M et al. RT-QuIC detection of CWD prion seeding activity in white-tailed deer muscle tissues. Sci. Rep. 2021 Aug 18;11(1):16759. doi: 10.1038/s41598-021-96127-8. PMID: 34408204; PMCID: PMC8373970.l

If you are interested in further details about microplate-based evaluation of prions and protein misfolding, please contact us at applications@bmglabtech.com or scan the QR code on the right-hand side

The post Investigating Prions and Protein Aggregation at High Sensitivity and Throughput appeared first on GEN - Genetic Engineering and Biotechnology News.

Messenger RNA (mRNA) is expanding from pandemic-scale vaccines toward a wider therapeutic portfolio. Recent Phase 3 success for an individualized neoantigen therapy from Moderna reinforces the clinical relevance of the lower-volume end of that spectrum, while COVID-19 established the opposite extreme. Clinical success is encouraging emerging and established developers to advance RNA medicines either through CDMOs or by building internal capacities. For increased development and production efficiency, CDMOs and drug developers need fast changeovers and flexibility across sequences and scales. All-ScaleFlow integrates RNA synthesis, purification, buffer exchange, and LNP formation to help democratize development.

A patented semi-continuous IVT core

RNA synthesis begins with fixed IVT unit volumes injected into Dillico’s patented, spiral-shaped semi-continuous reactor (Fig 1). The reactor is held in a temperature-controlled environment. Each unitary volume (UnV) advances by one loop periodically and the mature IVT crude UnV exits for optional enzymatic treatment and quenching. This design preserves defined batch reaction conditions without relying on progressively larger batch vessels.

Continuous purification and RNA-LNP formulation

As illustrated in the process flow diagram (Fig 2), All-ScaleFlow integrates alternating multi-column chromatography (dT Oligo resin or monolith) and multi-stage SPTFF for RNA purification, concentration, and buffer exchange. Surge tanks buffer cyclic chromatography eluate and maintain controlled flow into continuous purification SPTFF and LNP mixing. After encapsulation, a second multi-stage SPTFF step removes ethanol and performs final buffer exchange before in-line dilution or excipient addition and sterile filtration. By coordinating flow rates and interfaces, the platform maintains continuous production from IVT crude to formulated mRNA-LNP while minimizing intermediate holds.

Automated cleaning and sterilization onboard

To reduce supply chain risks and achieve long-term sustainability, an automated clean-in-place and sterilization-in-place (CIP/SIP) station is integrated on the system. It uses common cleanroom utilities to clean and sanitize the stainless-steel process path. This could save up to 450 kg of single-use plastic (~200 k$) for a large-scale batch IVT production.

Demonstrated across RNA sequence types

The synthesis approach has been successfully demonstrated with multiple mRNA and self-amplifying RNA (saRNA) sequences with length ranging from 400 bp to 12,000 bp. Working across different sequences is important for a platform intended to serve diverse vaccines and therapeutics.

The Process Simulator turns a sequence into a master recipe

Dillico’s Process Simulator embeds mechanistic process models built from an empirical knowledge base generated through experiments with mainstream, off-the-shelf process components. From product and process requirements, it calculates the global constraints needed to operate the continuous process as a coordinated system and identifies robust conditions that meet quality attributes and throughput targets. This reduces the physical experiments required during process development and supports right-first-time execution, avoiding costly trial-and-error with production materials and analytical testing. Thanks to the Process Simulator, users will be guided through a structured, step-by-step workflow that facilitates technology transfer and lowers the entry barrier for teams new to continuous processing. As part of the digital infrastructure, real process data are contextualized, making them data-lake-ready.

Explore All-ScaleFlowTM and request the Evidence Package

The post Inside All-ScaleFlow: Continuous End-to-End RNA-LNP Manufacturing appeared first on GEN - Genetic Engineering and Biotechnology News.

According to the company, the funds will support the development of what it claims is a first-of-its-kind platform for naturally modified mRNA medicines. The so-called Versatile Engine for Cell-based Therapeutic Optimization of RNA (VECTOR) platform integrates computational and artificial intelligence-enabled sequence optimization, high-throughput screening, and proprietary engineered eukaryotic cells to design and manufacture mRNA. Meanwhile, the company’s PromPT technology is designed to capture and protect mRNA inside cells before it is purified for therapeutic use. 

Specifically, Sensible will use the funds to expand VECTOR’s AI-enabled mRNA design and automated high-throughput screening capabilities as well as support the development of clinical-grade manufacturing capabilities. Sensible’s platform harnesses the natural machinery of living cells to produce naturally modified mRNA with reduced immunogenicity and high protein expression while avoiding double-stranded RNA contamination. Furthermore, by using engineered living cells, Sensible reduces reliance on specialized raw materials and manufacturing inputs, enabling more scalable production and expanding mRNA into therapeutic applications that require higher or repeated dosing.

Rather than relying on synthetic manufacturing technology developed more than 40 years ago, “we are taking a fundamentally different approach, using living cells to produce naturally modified mRNA while reducing the cost and supply-chain constraints of conventional production,” said Miroslav Gasparek, Sensible’s co-founder and CEO. “With this financing, we can scale our platform and expand mRNA into therapeutic applications requiring high or repeated dosing that have historically been limited by cost.”

The Series A includes participation from new investors OTB Ventures and In-Q-Tel, alongside existing investors Recode Ventures, Isomer Capital, Y Combinator, Backed VC, Kaya VC, Civilization Ventures, and BlueYard Capital, as well as the family office of Christoph Huber, co-founder of BioNTech, and Tim Garnett, former chief medical officer of Eli Lilly, and other individual investors.

In connection with the financing, Vishal Gulati, MD, FMedSci, managing partner at Recode Ventures, and Joel Schoppig, partner at Oxford Science Enterprises, will join Sensible’s board of directors alongside Miroslav Gasparek and Marian Kupculak, PhD, CSO and co-founder.

The post Sensible Biotechnologies Raises $47M to Expand Next-Generation Platform for mRNA Medicines appeared first on GEN - Genetic Engineering and Biotechnology News.

The scientists say the research creates one of the most comprehensive reference maps of early human embryo development, which they used to benchmark the biological accuracy of stem-cell-derived embryo models. They systematically evaluated four leading human blastoid-generation methods and found substantial differences in how faithfully they reproduce the cell types and developmental processes seen in natural human embryos.

Pengyi Yang, PhD, associate professor at the University of Sydney and an ARC Future Fellow in the School of Mathematics and Statistics and Unit Head of Computational Systems Biology at the Children’s Medical Research Institute, said the work gives scientists a more objective way to understand the strengths and limitations of embryo models. “Human embryo models have enormous potential for studying the earliest days of an embryo’s development, but there has been no consistent way to assess how accurately these reflect real human development. Our framework allows researchers to compare these models against a detailed biological reference and determine which cell types and developmental processes are faithfully reproduced, and which are not.”

Yang, who also leads the Trans-Regulatory Biology group at the Charles Perkins Centre, is senior and corresponding author of the team’s published paper in Cell Systems, titled “Systematic transcriptomic evaluation of blastoid models of early human development.” In their paper the team stated, “The reference map generated from this study enables the benchmarking of blastoids that may guide the optimization of the protocol for the generation of high-fidelity blastoid models that faithfully recapitulate the natural human blastocyst.”

The study of early human embryogenesis from blastocyst formation to gastrulation has been constrained by what the authors describe as “… technical challenges and ethical concerns associated with human embryo research.” But research on blastoid embryo models, which are derived from stem cells, offers scientists a way to study the biological events that underpin fertility, pregnancy success, and early human development without relying on donated human embryos.

While these research models are not actual human embryos—current models cannot develop into a human embryo—they could help answer questions that have long been difficult to investigate because of technical and ethical constraints. “Recent achievements in generating blastocyst-like structures from stem cells, the blastoids, that are reminiscent of human blastocysts in morphology and cellular composition have opened an avenue to glean knowledge of the biology of early human embryogenesis,” the team continued.

However, just because something looks like an embryo, does that mean it is behaving like one biologically? The University of Sydney team developed a computational framework that helps answer that question. “Establishing a systematic evaluation framework for assessing the fidelity of blastoids in modeling the human blastocyst is critical for enhancing the quality of these stem cell-based embryo models (SCBEMs),” they noted. “… we set out to develop a computational workflow for systematically assessing how closely blastoids generated by current state-of-the-art protocols recapitulate human blastocyst cell states and develop mental features.”

To do this the team combined and harmonized more than 14,000 single-cell transcriptomes—the set of RNA molecules in a cell—from human embryos spanning key stages of their development. This allowed them to create a reference map of how cells normally differentiate and organize themselves during the days immediately before and after implantation.

The investigators then compared that reference against four widely used blastoid-generation protocols developed by international research groups. Rather than assessing whether the models simply resembled embryos under a microscope, the researchers examined their molecular identities, developmental timing, lineage structure, and other biological characteristics.

The results showed that some blastoid models reproduced all three major cell lineages of a natural human blastocyst, or the early embryo, relatively well, while others failed to accurately represent certain cell types or contained large numbers of cells that could not be confidently matched to any known embryonic state. No single model perfectly replicated a natural human blastocyst. “Results of the benchmarking revealed substantial differences between protocols in recapitulating the composition, developmental timing, and coordinated lineage specification of the human blastocyst, highlighting that high-fidelity SCBEMs should reproducibly generate appropriately staged and developmentally coordinated blastocyst cell states,” the authors reported.

Yang said the findings highlight both the promise and current limitations of embryo models. “The encouraging finding is that some models capture important aspects of early embryonic development relatively well, although each model has limitations,” he said. “But our study also shows that current models are not biologically equivalent to real human embryos, and researchers need to be careful about the conclusions they draw from them.”

By providing a standardized benchmark, the researchers hope future models can be improved more rapidly and evaluated more rigorously. “Collectively, our work provides a comprehensive and systematic evaluation of the developmental authenticity of in vitro cultured SCBEMs generated by the state-of-the-art protocols,” they concluded. “Yang added, “If we’re going to use these systems to answer important biological questions, we first need to know what they can reliably tell us. Our work provides a roadmap for improving embryo models and ensuring scientific claims remain grounded in what the models can actually support.”

The researchers have made their reference datasets and benchmarking tools publicly available, enabling scientists worldwide to test new embryo models against the same standards.

The post A Method for Assessing Lab-Grown Stem Cell-Derived Embryo Models appeared first on GEN - Genetic Engineering and Biotechnology News.

Now, new research has revealed that bacteria detect viruses when a viral enzyme cuts an important sensor molecule in the bacterium, kicking off the immune response. Discoveries of bacterial defenses can pave the way for the development of better phage therapies that can evade the bacterial immune system.

The results are published in Science in the paper, “Phage proteases activate CBASS antiphage immunity.”

 “This is one of the most common forms of bacterial immunity, so when we finally figured it out, it was a total eureka moment,” said Sam Hobbs, PhD, assistant professor of biochemistry at University of Utah Health.

One component of the bacterial immune system is the cyclic oligonucleotide–based antiphage signaling systems (CBASS) which lead to a “last resort” immune response that kills the bacterium before viruses can spread to neighbors.

Precise sensing of the viral trigger is a necessity. In CBASS, cGAS/DncV-like nucleotidyltransferase (CD-NTase) enzymes sense phage infection and synthesize nucleotide signals to initiate antiviral defense. This new work found that the sensing mechanism detects a molecule that the virus needs to survive. More specifically, that phage prohead protease activity is a widespread mechanism of CD-NTase activation.

“We found that the protease from the phage actually acts directly on the host protein, and that is the signal that turns on the whole signaling pathway,” explained Hobbs.

This trigger mechanism is distinct when compared to related antiviral immune pathways, which are activated by the presence of viral genetic material. “This is a totally new mechanism for how these host proteins are activated,” Hobbs said.

Hobbs added that understanding CBASS may advance our knowledge of the human immune system. CBASS is related to a similar immune pathway in humans, indicating that this pathway has persisted at least since bacteria and humans had a common ancestor. And because bacteria have such a rapid life cycle, scientists can use them to very quickly answer questions about how the immune system works, which they can then test in models closer to people.

“The fact that these systems are conserved between bacteria and humans suggests that they’ve been maintained in these different organisms for that entire evolutionary trajectory,” Hobbs said. “The cells are telling us that this is a really important pathway because they’ve maintained it for billions of years. It’s incredibly fascinating, and it’s a cool window into what’s important in maintaining the ability to fight viruses.”

The post Phage Proteases Trigger a Conserved Bacterial Antiviral Defense Pathway appeared first on GEN - Genetic Engineering and Biotechnology News.

Using live cultures of human brain cells and slices of brain tissue obtained during neurosurgery, the researchers, headed by Nicholas Barnes, PhD, professor at the University of Birmingham College of Medicine and Health, investigated the role of the P2X7 receptor, which is responsible for triggering inflammatory signaling. Their findings revealed that these P2X7 receptors drive the release of cytokines involved in controlling inflammation. By blocking this receptor with a specific antagonist, the team was able to significantly reduce the inflammatory response in human brain tissue.

The team suggests that their results could open the door to treating a wide spectrum of chronic neurological conditions, including TBI, neurodegenerative diseases, and even psychiatric disorders such as depression and psychosis, which are increasingly understood to have a neuroinflammatory component.

Barnes said, “This exciting discovery marks a major step toward repurposing existing therapeutics to combat neuroinflammation at its source. The identification of this receptor could have far-reaching implications for some of the most debilitating and widespread brain disorders such as Alzheimer’s disease, Parkinson’s, and multiple sclerosis, or inflammation-linked psychiatric conditions like schizophrenia and depression.”

Barnes is senior and corresponding author of the team’s published paper in Brain, titled “P2X7 receptor-mediated IL-1β release by human brain tissue: the impact of CNS-penetrant potential therapeutics,” in which they concluded “Our findings provide direct relevant evidence for the use of P2X7R antagonism to inhibit human microglia-mediated inflammation, with arising potential benefits for patients with TBI and other neuroinflammatory diseases.”

TBI is a major cause of death globally, and there are currently there are no approved therapeutic drugs to improve clinical outcomes, “… emphasizing the clear unmet substantial clinical need,” the authors wrote.

The mechanical damage associated with TBI drives a neuroinflammatory response. “The purinergic P2X7 receptor (P2X7R) is a key driver of neuroinflammation in a range of animal models of traumatic brain injury,” the team continued. P2X7R is expressed by microglia, the resident immune cells in the CNS that are involved in many developmental, homeostatic and pathological roles. “It is well recognized that microglial activation and the hostile neuroinflammatory response arising after the initial insult provide a therapeutic window for pharmacological intervention,” the investigators further stated.

For their reported study investigating how brain cells respond to and manage inflammation, the team developed a way of turning a type of white blood cell into microglia, replicating a normal cellular transformation that has recently been identified to occur in the brain as a natural part of human aging. These microglia are the central coordinators of the immune system in the brain.

Using readily accessible human peripheral monocytes taken from blood samples, the researchers converted them into microglia-like cells—human monocyte-derived microglia (hMDM)—that were used to see how microglia are likely to respond to the inflammation signals. “This enabled us to demonstrate the ability of clinically relevant P2X7R antagonists, including brain-penetrant molecules, to curtail pro-inflammatory cytokine release,” they wrote.

The team showed that administering a P2X7 receptor antagonist interrupted the triggers that these microglia give off as they are damaged and die. Barnes said, “Studying human microglia has long been a major challenge: once removed from their native brain environment, they rapidly lose their defining characteristics, likely due to the absence of critical regulatory signals. Our approach involved the use of monocyte-derived microglia which provide a powerful, scalable, and virtually unlimited platform for studying human microglial biology with unprecedented precision.”

The team confirmed their results using adult human precision-cut brain slices that had been generated subsequent to neurosurgical resections. “Having identified the response in the human monocyte-derived microglia, this provided the impetus to translate these findings with human brain obtained following neurosurgical procedures, Barnes continued. “This successful translation means the next stage for this research is the development of clinical trials in patients with neurodegenerative conditions and patients with TBI where there are no effective pharmacological treatments to reduce the neuroinflammation and arising damage.”

In their paper the authors concluded, “The present study provides direct translational evidence from human cellular and brain tissue models to support the clinical use of P2X7R antagonists to limit secondary ATP-driven neuroinflammatory events, such as those that occur in TBI, and thus might improve the clinical outcomes for patients.”

The post Anti-Inflammatory Drug Target for Alzheimer’s, TBI, and Neurodegenerative Disease Identified appeared first on GEN - Genetic Engineering and Biotechnology News.