Best of the Week: RNA-Based Therapeutics, GLP-1 Treatment

This past week, LCGC International published a variety of articles on hot topics in separation science. Judith Hey-Hadavi, vice president of Medical Affairs at Worldwide Clinical Trials, and Nicole Snow, clinical pharmacist at Olympia Pharmaceuticals, lead a discussion about GLP-1 therapies, and we present a few clips from that Peer Exchange™ here. Also, a recent interview with IQ Consortium’s Nucleic Acid Working Group explores the current challenges and best practices in the bioanalysis of nucleic acid–based therapeutics.

This is the Best of the Week.

Advancing RNA-Based Therapeutics: IQ Consortium Experts on Optimizing Chromatographic Bioanalysis

This interview explores current challenges and best practices in the bioanalysis of nucleic acid–based therapeutics such as siRNAs and antisense oligonucleotides. Three experts from the IQ Consortium’s Nucleic Acid Working Group, which included Vibha Jawa of EpiVax (Providence, Rhode Island), Shirin Hooshfar of Eli Lilly and Company (Indianapolis, Indiana), and Wenying Jian of Johnson & Johnson Innovative Medicine (Spring House, Pennsylvania), discussed their motivation for publishing a white paper aimed at standardizing absorption, distribution, metabolism, and excretion (ADME), drug metabolism and pharmacokinetics (DMPK), and clinical pharmacology strategies as the field rapidly expands (1). They highlighted key chromatographic issues, including poor retention, ion suppression, and complex charge states, and explain how ion-pair reagents, temperature control, and hybridization-based extraction can improve liquid chromatography–mass spectrometry (LC–MS) performance (1). The discussion compares LC–MS/MS and high-resolution MS for quantitation and metabolite identification, emphasizes the importance of deconvolution software, and explains why stable isotope–labeled standards are difficult to produce for oligonucleotides (1).

Navigating Adverse Reactions in GLP-1 Treatment

In this clip from a recent LCGC International Peer Exchange™, it examines why GLP-1 therapies cause gastrointestinal side effects and how clinicians can minimize them through careful titration, monitoring, and patient-specific adjustments (2). Nicole Snow highlights individualized dosing strategies based on real-time patient response, while Judith Hey-Hadavi stresses the importance of integrating safety data with clinical judgment and setting realistic expectations (2). Together, they emphasize that factors such as dose, treatment history, and patient physiology strongly influence tolerability and shape the overall safety profile of GLP-1 treatments.

Shifting GLP-1 Receptor Agonists from Proteins to Small Molecules

In episode 2 of the GLP-1 Peer Exchange™ features Judith Hey-Hadavi and Nicole Snow discussing the transition of GLP-1 therapies from injectable protein-based drugs to emerging small-molecule and oral options (3). They examine how patient preferences are driving demand for oral formulations and review the challenges of achieving sufficient bioavailability and maintaining tolerability. The experts outline clinical strategies, such as careful dose titration, lifestyle guidance, and proactive side-effect management, to help optimize outcomes (3). Throughout the conversation, they emphasize the need to balance efficacy, safety, and adherence as GLP-1 therapies continue to evolve.

Chromatography Maps Metabolic Crosstalk Between Coral Tissue and Endolithic Bacterial Communities

Researchers in Taiwan used Isopora palifera, a coral species lacking microalgae in its skeleton, to investigate the ecological role of endolithic bacteria. Using gas chromatography time-of-flight mass spectrometry (GC-TOF-MS), ultrahigh-pressure liquid chromatography tandem mass spectrometry (UHPLC-MS/MS), and stable isotope tracers (¹³C and ¹⁵N), they identified distinct metabolic profiles in coral tissue and skeletal layers and documented carbon, but not nitrogen (4). The findings show that carbon-based metabolites such as carbohydrates and bioactive compounds move from the green sulfur bacterial layer to coral tissue, while some nitrogenous compounds originate from the skeleton (4). Antibiotic treatments altered nitrogen movement, revealing bacteria’s key role in nitrogen cycling. The study provides the first metabolomic data for coral skeletons and proposes a new model for coral–bacteria interactions.

Decoding Sweet Potato Drought Resilience: Metabolomic Evidence from UPLC-MS Profiling

A recent study examined metabolic responses to early drought stress in drought-tolerant (Atacama) and drought-susceptible (Blesbok) sweet potato cultivars using untargeted ultra-performance liquid chromatography-mass spectrometry (UHPLC-MS). Chemometric analyses revealed clear metabolic differences between cultivars and stress levels, identifying ten significantly regulated metabolites, particularly flavonoids, sugars, and glycolipids, as potential biomarkers of drought tolerance (5). Key pathways included flavonoid and zeatin biosynthesis and starch and sucrose metabolism. Although plants showed no visible phenotypic changes, molecular differences highlight the value of metabolomics for uncovering hidden stress responses (5). The findings support future breeding programs and targeted metabolomics approaches to improve sweet potato drought resilience and enhance food security.

References

1. Hroncich, C. Advancing RNA-Based Therapeutics: IQ Consortium Experts on Optimizing Chromatographic Bioanalysis. LCGC International. Available at: https://www.chromatographyonline.com/view/advancing-rna-based-therapeutics-iq-consortium-experts-on-optimizing-chromatographic-bioanalysis (accessed 2025-12-04).
2. Hey-Hadavi, J.; Snow, N. Navigating Adverse Reactions in GLP-1 Treatment. LCGC International. Available at: https://www.chromatographyonline.com/view/navigating-adverse-reactions-in-glp-1-treatment (accessed 2025-12-04).
3. Hey-Hadavi, J.; Snow, N. Shifting GLP-1 Receptor Agonists from Proteins to Small Molecules. LCGC International. Available at: https://www.chromatographyonline.com/view/glp-1-receptor-agonists-small-molecules-oral-therapies (accessed 2025-12-04).
4. Chasse, J. Chromatography Maps Metabolic Crosstalk Between Coral Tissue and Endolithic Bacterial Communities. LCGC International. Available at: https://www.chromatographyonline.com/view/chromatography-maps-metabolic-crosstalk-between-coral-tissue-and-endolithic-bacterial-communities (accessed 2025-12-04).
5. Chasse, J. Decoding Sweet Potato Drought Resilience: Metabolomic Evidence from UPLC-MS Profiling. LCGC International. Available at: https://www.chromatographyonline.com/view/decoding-sweet-potato-drought-resilience-metabolomic-evidence-from-uplc-ms-profiling (accessed 2025-12-04).