Publications by authors named "Katelyn J Smith"
Article Synopsis
- - The study focuses on the fibrillation of therapeutic peptides, specifically a 29-residue peptide called PepA and its modified versions, PepB and PepC, to understand how structural changes can influence fibrillation and improve drug development.
- - Different modifications, such as amidation of PepA's C-terminus and the substitution of Ser16 in PepC, were analyzed through various techniques, revealing that PepA and PepB formed fibrils while PepC did not and remained structurally stable.
- - Real-time stability analyses indicated that differences in peptide charge and formulation pH affected fibrillation rates, with stress tests revealing the presence of previously undetectable oligomers, suggesting that formulation stability is crucial for preventing fibrillation during storage
Enabling online determination of the size-dependent RNA content of lipid nanoparticle-based RNA formulations.
J Chromatogr B Analyt Technol Biomed Life Sci
December 2021
The potential of lipid nanoparticles (LNPs) as nucleic acid delivery vehicles has been demonstrated in recent years, culminating in the emergency use approval of LNP-based mRNA SARS-CoV-2 vaccines in late 2020. The determination of RNA content relative to LNP size can be important to the understanding of efficacy and adverse effects. This work presents the first description of a facile and rapid analytical method for online, size-dependent RNA payload distribution measurement using data from multi-angle light scattering, ultraviolet and refractive index detectors following separation of the LNPs by size-exclusion chromatography.
View Article and Find Full Text PDFThe presence of subvisible or visible particles in mAb formulations can pose significant challenges to pharmaceutical development as it can lead to reduced shelf life, batch rejection, and recalls. Among all type of particles, proteinaceous particles are the most concerning due to their potential role in immunogenicity. Nevertheless, the underlying mechanism for protein particle formation remains poorly understood.
View Article and Find Full Text PDFGlucagon and insulin maintain blood glucose homeostasis and are used to treat hypoglycemia and hyperglycemia, respectively, in patients with diabetes. Whereas insulin is stable for weeks in its solution formulation, glucagon fibrillizes rapidly at the acidic pH required for solubility and is therefore formulated as a lyophilized powder that is reconstituted in an acidic solution immediately before use. Here we use solid-state NMR to determine the atomic-resolution structure of fibrils of synthetic human glucagon grown at pharmaceutically relevant low pH.
View Article and Find Full Text PDFArticle Synopsis
- Peptides and proteins can adopt various complex structures, which can lead to harmful forms like aggregates and fibrils that affect drug development and disease.
- Liraglutide, a drug for diabetes, forms oligomers that can be stabilized by factors like pH and solvents, and these oligomers can influence the drug's stability and effectiveness.
- Our research highlights how Liraglutide's "oligomer memory effect" from its synthesis process is crucial for understanding its behavior, which has implications for the entire drug development process.
Background: The FRG1-transgenic mouse displays muscle dysfunction and atrophy reminiscent of fascioscapulohumeral muscular dystrophy (FSHD) and could provide a model to determine potential therapeutic interventions.
Methods: To determine if FRG1 mice benefit from treatments that improve muscle mass and function, mice were treated with creatine alone (Cr) or in combination with treadmill exercise (CrEX).
Results: The CrEx treatment increased quadriceps weight, mitochondrial content (cytochome c oxidase (COX) activity, COX subunit one and four protein), and induced greater improvements in grip strength and rotarod fall speed.