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Galley, C.

Publications and source records attributed to Galley, C..

2 recordsLinked to original sources
bioRxiv2026

Poly(acrylamido) PEG-alternatives Enhance mRNA-LNP Efficacy in Immune Cells and Evade anti-PEG Antibodies During Repeated Dosing

Following the successes of the messenger RNA (mRNA) lipid nanoparticle (LNP) vaccines during the COVID-19 pandemic, mRNA-LNPs are being explored for many critical disease indications including infectious disease vaccination, cancer immunotherapies, and protein replacement therapies. LNPs require a polymer coating to provide stability in storage, and to minimise clearance from the body by reducing protein adsorption after injection. Poly(ethylene glycol)-lipids (PEG-lipids) have fulfilled this role to date, however increasing prevalence of antibodies against PEG in the general population jeopardises the efficacy of future PEGylated LNP doses and increases the likelihood of adverse pseudo-allergic responses. There is, therefore, an urgent unmet need to develop LNPs with new surfaces of PEG-alternative polymers which can evade anti-PEG antibodies, particularly where repeat dosing is required. Here, we present a family of polymer lipids, poly(acrylamido) (PAM) lipids, which effectively replace conventional PEG-lipids in mRNA-LNP formulations. We identify key design parameters to show that PAM-lipid monomer chemistry, molar mass and end-group all have critical effects on LNP size, polydispersity and in vitro transfection efficiencies, while having little impact on LNP morphology or internal structure. We determine that side-group (monomer) chemistry is a key mediator in alleviating anti-polymer antibody cross-reactivity. Compared to clinical benchmark PEGylated LNPs, several PAM-LNPs displayed improved transfection efficacy across multiple mRNA cargos in diverse cell types, organs, and routes of administration, both in vitro and in vivo. In particular, mRNA transfection improved in immune cells both in vitro (up-to 120-fold), and in vivo (up-to 5-fold), including superior mRNA expression in lymph nodes (2.5-fold). In part, this is likely because PAMs increase LNP uptake/association with primary immune cells (BMDCs), and increase biodistribution to the lymphoid tissues (LNs, spleen). Crucially, PAM-LNPs avoid circulating anti-PEG antibodies to recover lost mRNA efficacy after repeated dosing in vivo, 300% higher than PEG-LNPs. Overall, our findings establish the PAM-lipid family as a versatile platform of chemically varied PEG-alternatives, towards the next generation of therapeutic mRNA-LNP technologies. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=103 SRC="FIGDIR/small/708093v1_ufig1.gif" ALT="Figure 1"> View larger version (31K): org.highwire.dtl.DTLVardef@107de1aorg.highwire.dtl.DTLVardef@186b6eforg.highwire.dtl.DTLVardef@1542371org.highwire.dtl.DTLVardef@e2d47f_HPS_FORMAT_FIGEXP M_FIG C_FIG

bioengineering↗
bioRxiv2025

Potential benefits of Soymilk-burkina (Agbenu) consumption on gut health of women of reproductive age

BackgroundGut microbiome plays a crucial role in human health. This study investigated the impact of two soy-based foods, soymilk-burkina (SMB), a traditional fermented Ghanaian beverage) and soymilk-millet blend (SMMB), on the gut microbiome of women of reproductive age. MethodsFecal samples were collected from two cohorts of women consuming either SMB or SMMB soymilk-burkina or a soymilk-millet blend) at 2 weeks pre-intervention, baseline, during an 8-week intervention, and 4 weeks post-intervention. 16S rRNA gene amplicon sequencing was used to analyze the composition and diversity of the gut microbiome. Results{beta}-diversity analysis revealed no significant differences in overall community composition between the two cohorts. -diversity indices (Chao1, Shannon, Simpson) showed no significant differences in richness, evenness, or diversity between cohorts, suggesting a balanced gut ecosystem after both interventions. However, 20 dominant bacterial species were identified, including both beneficial (e.g., Faecalibacterium prausnitzii and Bacteroides vulgatus) and potentially harmful (e.g., Eubacterium rectale and Bacteroides fragilis) taxa. Soymilk-burkina consumption of soymilk-burkina significantly reduced the abundance of Eubacterium rectale (associated with colon cancer) and increased the abundance of F. prausnitzii (beneficial), suggesting potential gut health benefits. However, these effects were transient, highlighting the need for sustained dietary interventions. ConclusionThis study provides insights into the dynamic interplay between diet and the gut microbiome, particularly in the context of traditional fermented foods such as soymilk-burkina. Although short-term changes were observed, the long-term benefits may require consistent consumption. Further research is required to explore the mechanisms underlying these effects and their implications on broader health outcomes. Plain Language SummaryThe human body, particularly the gastrointestinal tract, hosts trillions of microorganisms, predominantly bacteria. These "gut microbes" play a crucial role in nutrient digestion, vitamin synthesis, and disease prevention. Dietary intake can significantly alter the composition of these microbial communities. This study investigated whether a traditional fermented beverage, soymilk-burkina, could enhance the gut health of women in Ghana. A comparative unfermented soymilk-millet blend was also examined. Forty women were randomly assigned to two groups, each consuming one of the soy beverages daily for an eight-week period. Fecal samples were collected at baseline, during, and after the intervention to analyze bacterial profiles. The results indicated no dramatic overall changes in the diversity or types of gut bacteria between the two groups. However, women who consumed fermented soymilk-burkina exhibited notable shifts, specifically a reduction in Eubacterium rectale, a bacterium associated with colon cancer, and an increase in beneficial Faecalibacterium prausnitzii, known for its positive impact on gut health. These positive alterations, however, appeared to be transient. Approximately one month after discontinuing the fermented product, the participants gut bacterial levels began reverting to their pre-study states. In conclusion, this study suggests that fermented soymilk-burkina may offer short-term benefits to gut health by promoting beneficial bacteria and reducing potentially harmful ones. Nevertheless, sustained consumption of this beverage is necessary to maintain these benefits. This research underscores the influence of diet on gut microbiota and highlights the potential of traditional fermented foods like soymilk-burkina for further exploration, although more research, particularly concerning long-term effects, is warranted.

microbiology↗