Advances in endotoxin analysis

Sondhi, Palak; Adeniji, Taiwo; Lingden, Dhanbir; Stine, Keith J.

doi:10.1016/bs.acc.2023.11.001

Cited by 3 publications

(2 citation statements)

References 146 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…They are composed of lipopolysaccharide (LPS), consisting of an acylated backbone (lipid A) responsible for the induction of a proinflammatory immune response, a chain of repeated sugar units (O-antigen) and an oligosaccharide core ( O'Neill et al, 2013 ; Cavaillon, 2018 ; Sondhi et al, 2024 ). If present, LPS contaminants can interact with LPS-binding protein (LBP), Myeloid differentiation protein 2 (MDA2), CD14 and Toll-Like Receptor 4 (TLR4), thereby leading to signal transduction through the TRIF and MyD88 pathways, resulting in the secretion of proinflammatory cytokines such as IL-6, TNF-α, and IL-1 ( O'Neill et al, 2013 ; Sondhi et al, 2024 ). In addition, LPS can interact with caspase-4 in mice or caspase-4/5 in humans, leading to inflammasome activation and IL-1α and IL-1β release ( Kayagaki et al, 2011 ; Viganò et al, 2015 ).…”

Section: Ivt Reaction Contaminants/impurities Of Non-nucleotide Natur...mentioning

confidence: 99%

“…In addition, LPS can interact with caspase-4 in mice or caspase-4/5 in humans, leading to inflammasome activation and IL-1α and IL-1β release ( Kayagaki et al, 2011 ; Viganò et al, 2015 ). Endotoxin is extremely potent, where even amounts as low as 0.1–0.5 ng/kg can lead to cytokine release, and dose-dependent side effects such as fever, chills, nausea, hypotension, tissue damage, sepsis, and death might occur ( Elin et al, 1981 ; Sondhi et al, 2024 ). Thus, the upper limits and acceptance criteria as well as analytical methods for measuring endotoxin are strictly defined per USP chapter <85> Bacterial Endotoxins Test 3 (BET) based on dose, application route and type ( Dawson, 2017 ).…”

Section: Ivt Reaction Contaminants/impurities Of Non-nucleotide Natur...mentioning

confidence: 99%

See 1 more Smart Citation

Understanding the impact of in vitro transcription byproducts and contaminants

Lenk,

Kleindienst,

Szabó

et al. 2024

Front. Mol. Biosci.

View full text Add to dashboard Cite

The success of messenger (m)RNA-based vaccines against SARS-CoV-2 during the COVID-19 pandemic has led to rapid growth and innovation in the field of mRNA-based therapeutics. However, mRNA production, whether in small amounts for research or large-scale GMP-grade for biopharmaceutics, is still based on the In Vitro Transcription (IVT) reaction developed in the early 1980s. The IVT reaction exploits phage RNA polymerase to catalyze the formation of an engineered mRNA that depends on a linearized DNA template, nucleotide building blocks, as well as pH, temperature, and reaction time. But depending on the IVT conditions and subsequent purification steps, diverse byproducts such as dsRNA, abortive RNAs and RNA:DNA hybrids might form. Unwanted byproducts, if not removed, could be formulated together with the full-length mRNA and cause an immune response in cells by activating host pattern recognition receptors. In this review, we summarize the potential types of IVT byproducts, their known biological activity, and how they can impact the efficacy and safety of mRNA therapeutics. In addition, we briefly overview non-nucleotide-based contaminants such as RNases, endotoxin and metal ions that, when present in the IVT reaction, can also influence the activity of mRNA-based drugs. We further discuss current approaches aimed at adjusting the IVT reaction conditions or improving mRNA purification to achieve optimal performance for medical applications.

show abstract

Section: Ivt Reaction Contaminants/impurities Of Non-nucleotide Natur...mentioning

confidence: 99%

Section: Ivt Reaction Contaminants/impurities Of Non-nucleotide Natur...mentioning

confidence: 99%

Understanding the impact of in vitro transcription byproducts and contaminants

Lenk,

Kleindienst,

Szabó

et al. 2024

Front. Mol. Biosci.

View full text Add to dashboard Cite

show abstract

Exploring glycans as vital biological macromolecules: A comprehensive review of advancements in biomedical frontiers

Arora,

Sherilraj,

Abutwaibe

et al. 2024

International Journal of Biological Macromolecules

View full text Add to dashboard Cite

A compact prism-based microscope for high sensitive measurements in fluid biopsy

Perego,

Dallari,

Falciani

et al. 2024

Preprint

View full text Add to dashboard Cite

The increasing demand for sensitive, portable, and cost-effective disease detection methods has raised significant interest in the development of biosensors for rapid and early-stage diagnosis, population mass-screening, and bedside monitoring. Although a certain number of sensing devices with high sensitivity has experienced considerable progress, their practical application has been hindered by challenges in replicating instrumental systems, obtaining rapid and multiplexed signals, and the high cost of manufacturing. In response, we present a streamlined prism-based Total Internal Reflection system which, in combination with surface functionalization techniques on gold nanoparticles, is capable of facilitating Evanescent Wave scattering for the highly sensitive and rapid detection of specific analytes in synthetic liquids and real human samples. The system achieves a remarkable limit of detection of 1 fg/mL concentration for the targeted pathological biomarker. Our innovative design addresses the limitations of existing technologies by reducing costs, minimising overall size, and ensuring swift biofluid analysis with remarkable sensitivity. To validate its efficacy, we conducted scattering experiments in synthetic and human serum samples, exploiting functionalized AuNPs to recognize bacterial lipopolysaccharides as biomarkers for sepsis disease. The cohesive integration of these techniques hopefully makes this biosensing setup a promising candidate for potential clinical deployment, meeting the pressing requirements for rapid personalised diagnosis, large-scale population screening and bed-monitoring.

show abstract

Advances in endotoxin analysis

Cited by 3 publications

References 146 publications

Understanding the impact of in vitro transcription byproducts and contaminants

Understanding the impact of in vitro transcription byproducts and contaminants

Exploring glycans as vital biological macromolecules: A comprehensive review of advancements in biomedical frontiers

A compact prism-based microscope for high sensitive measurements in fluid biopsy

Contact Info

Product

Resources

About