Integrating Omics Data Through AI Predicting Novel Therapeutic Targets for Therapy-Resistant Cancer Patients
Artificial intelligence (AI) is transforming biomedicine by facilitating the thorough analysis of multi-omics data, thereby deepening our grasp of intricate biological systems and the underlying mechanisms of diseases. Our study leverages AI to synthesize diverse omics datasets— including genomics, proteomics, and metabolomics—with the goal of identifying novel therapeutic targets for cancer patients resistant to current treatments. This strategy is designed to enhance the development of personalized medicine and refine treatment approaches, offering new avenues for addressing complex medical challenges.
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Exploring the Spatial Distribution of mRNA-Lipid Nanoparticles in Mouse Whole-Body and Isolated Organs Using MALDI MSI
To investigate the biodistribution and potential toxicity of lipid nanoparticles (LNP1 and LPN2), which are crucial carriers for mRNA-based treatments after administration to male and female mice, by analyzing their distribution in whole-body carcasses and specific organs using MALDI-MSI.
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Elucidating the Role of IL-18 in NSCLC Integrated Analysis through Imaging Mass Cytometry, Mass Cytometry, and Single-Cell Sequencing
Interleukin-18 (IL-18) plays a pivotal role in nonsmall cell lung cancer (NSCLC) progression, influencing both tumor growth and immune response dynamics. Recent insights into the heterogeneity and functional status of tumorinfiltrating T cells have underscored their critical impact on antitumor immunity and responses to immunotherapy, paralleling the observed complexity in IL-8 interactions within the tumor microenvironment. This study employs Imaging Mass Cytometry (IMC), Mass Cytometry (CyTOF), and Single-Cell RNA Sequencing (scRNA-seq) to map IL-18 expression, explore its impact on immune cell subsets, and identify its role in the tumor microenvironment
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Distribution of Standard-of-Care Antituberculosis Drugs in Cynomolgus Macaque Lungs
The non-human primate (NHP) provides the most clinically relevant model of human tuberculosis. The aim of this study was to determine the tissue pharmacokinetics of orally delivered isoniazid (H), rifampicin (R), pyrazinamide (Z) and ethambutol (E) combination therapy (HRZE) in the lung of cynomolgus macaques to prepare following studies in Mycobacterium tuberculosis-infected animals usinq QMSI.
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Development of Quantitative MALDI Mass Spectrometry Imaging Methods for Studying Distribution of Antituberculosis Drugs at their Site of Action
Tuberculosis (TB), caused by Mycobacterium tuberculosis (MTb), remains a global health challenge, with treatment involving a year-long regimen of four drugs: Isoniazid, Rifampicin, Pyrazinamide, and Ethambutol. However, the emergence of drug resistance calls for the development of new therapeutic molecules. Due to the complex granulomatous lesions formed by MTb, plasma drug concentrations often do not reflect tissue drug levels, making it crucial to assess drug exposure at the site of action. To address this, we have developed Mass Spectrometry Imaging (MSI) methods to study the distribution of anti-TB drugs and their metabolites, including pyrazinoic acid, across both healthy and diseased tissues.
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Development of a Mitra Tip Extraction Assay Coupled with LC-MSMS
Biomarkers such as L-Citrulline, L-Arginine, and L-Argininosuccinic Acid play crucial roles in various physiological processes and pathological conditions. However, their accurate quantitation presents challenges due to sample complexity and low concentrations. Here, we present a novel approach utilizing Mitra tip extraction coupled with liquid chromatography-tandem mass spectrometry (LC-MS/MS) for the simultaneous quantitation of these biomarkers. Mouse models are known to produce small blood volumes while Mitra tips offer advantages in sample collection, allowing for convenient and reproducible extraction from biological matrices.
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A Derivatization-free LCMS Assay for 4β-hydroxycholesterol
In clinical studies, 4β-hydroxycholesterol is an important biomarker for assessing the activity of CYP3A. Numerous quantitative methods have been reported for analyzing the total amount of 4β-hydroxycholesterol (free and conjugated) after saponification and derivatization. Derivatization is often required to achieve clinically relevant assay sensitivity when utilizing LCMS for detection, but this additional step can be complex and time-consuming.
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LC/MS Method for the Measurement of Ornithine Carbamoyl transferase Enzymatic Activity Levels in Human Plasma
Aliri Bioanalysis scientists at our Colorado Springs lab recently developed and validated an enzyme activity assay for ornithine transcarbamylase (OTC) in human plasma by taking advantage of mass spectrometry’s unique mass-resolving power. This work used human plasma in lieu of tissue biopsies for activity assessments and suggested that OTC activity in plasma could be used as a pharmacodynamic endpoint for OTC Deficiency treatment.
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Phenyl SPE: A Promising Alternative to More Common Oligonucleotide Extraction
Chemical modifications made to oligonucleotides can assist in absorption, distribution, and metabolism. While many oligonucleotide-based drugs share similarities in extraction and ionization techniques, the properties of the matrix itself are often overlooked. The extraction of a variety of oligonucleotides using a standard Clarity OTX solid phase extraction plate has been more commonplace in bioanalytical laboratories. These plates have been shown to isolate RNA and DNA-based therapeutics from biological fluids and tissues in a short period of time with high recovery percentages and standard extraction buffers. Here we show an alternate extraction method for a novel antisense oligonucleotide (ASO) in spinal cord and brain tissues.
Originally, acceptable and reproducible results were obtained by using a Clarity OTX SPE plate with non-human primate cerebral spinal fluid and brain tissue homogenate. The extraction was modified in mouse brain tissue to a liquid-liquid method involving phenol-chloroform. Further optimization in spinal cord tissue, however, required a more robust method using a phenyl solid-phase extraction (SPE) plate, triethylammonium acetate buffer (TEAA), and a protein precipitation filter plate.
LBA vs LC-MS: competing technologies at a development crossroad
The Aliri team recently hosted this webinar to discuss why so many sponsors are now reconsidering the use of Ligand-Binding Assays (LBA) for the vast majority of large molecule protein analysis given the many compelling benefits Liquid Chromatography-Mass Spectrometry (LC-MS) can provide in terms of speed, cost, and data specificity.
Watch this on-demand webinar with bioanalytical experts Shane Karnik, MS, and Matt Hartle, PhD, to learn more about the changing market landscape, pros and cons for each technology, and why you should consider LC-MS over LBA for your next large molecule program.
This webinar also explores:
• advancements in biomarker discovery, validation and quantification using LC-MS technologies, and
• complexities of analyzing transgenic expressed proteins, focusing on the differences between human and endogenous proteins, with a special emphasis on mRNA drugs.
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CONTACT US to learn more about Aliri’s extensive experience with this technology.