Journal: bioRxiv

Article Title: Combinatorial base editing couples disease correction with lineage amplification in hematopoietic stem and progenitor cells

doi: 10.64898/2026.04.13.718029

Figure Lengend Snippet: A. Editing frequencies at the EPOR-sg1 locus measured at Day 4 post-electroporation with CBE6 mRNA prepared under different conditions, including capping strategies (CleanCap AG), incorporation of modified nucleotides (e.g., pseudouridine), RNase inhibitor addition, freeze-thaw cycles, and storage duration. B. Heatmaps showing EPOR -sg1 editing frequencies across varying CBE6 mRNA doses (2-10 µg) and electroporation conditions using Lonza 4D nucleofector with P3 buffer + DZ-100 code or B1mix buffer + CM-137 code. Data are shown as replicate measurements from a single donor (n = 1).

Article Snippet: In vitro transcription (IVT) was performed using the HiScribe T7 High Yield RNA Synthesis Kit or the HiScribe T7 mRNA Kit with CleanCap AG (New England Biolabs; E2040 or E2080).

Techniques: Electroporation, Modification

Journal: Advanced Healthcare Materials

Article Title: CORE: Cholesterol Altered Lipid Nanoparticles for Splenic Expression of mRNA Payloads

doi: 10.1002/adhm.202505862

Figure Lengend Snippet: Development of heterocyclic cholesterol derivatives enabling the development of CORE LNPs for mRNA expression in the spleen.

Article Snippet: CleanCap Firefly luciferase (FLuc) mRNA (5‐moU) was purchased from Hongene Biotech.

Techniques: Expressing

Journal: Advanced Healthcare Materials

Article Title: CORE: Cholesterol Altered Lipid Nanoparticles for Splenic Expression of mRNA Payloads

doi: 10.1002/adhm.202505862

Figure Lengend Snippet: (a) Schematic workflow for CORE LNP formulation development. (b) Chemical structures of the components used to form CORE LNPs where each particle contains SM‐102, its respective cholesterol derivative ( C1‐6 ), DSPC or DOPE, and 14:0 PEG 1K. (c) CORE LNP size (nm), charge (mV), and % mRNA encapsulation for each respective formulation. (d) 24 h FLuc expression of respective CORE LNPs treated on DC 2.4 cells at a dose of 50 ng FLuc mRNA. (e) Heat map representation of FLuc expression for all 78 CORE LNP formulations. (f) Multivariate analysis of CORE LNP expression as a function of size, charge, and % mRNA encapsulation. (All data represented as the mean ± standard deviation, n =4, * p <0.05 as compared to naked mRNA treatment group using one‐way ANOVA, Dunnett's test).

Article Snippet: CleanCap Firefly luciferase (FLuc) mRNA (5‐moU) was purchased from Hongene Biotech.

Techniques: Formulation, Encapsulation, Expressing, Standard Deviation

Journal: Advanced Healthcare Materials

Article Title: CORE: Cholesterol Altered Lipid Nanoparticles for Splenic Expression of mRNA Payloads

doi: 10.1002/adhm.202505862

Figure Lengend Snippet: (a) Schematic overview of cellular uptake assay. (b) Schematic overview of cellular uptake mechanism assay. (c) Evaluation of cellular uptake of CORE LNPs encapsulating Cy‐5 labeled FLuc mRNA at 2 and 24 h on DC 2.4 cells. (d) Elucidation of the cellular uptake mechanism of respective CORE LNPs using inhibitors: Pitstop 2 (clathrin‐mediated endocytosis), EIPA (macropinocytosis), filipin (caveolae‐mediated endocytosis), and cytochalasin D (phagocytosis) treated on DC 2.4 cells. (All data represented as the mean ± standard deviation, n = 4). * p <0.05 as compared to SM‐102 LNP treatment group using one‐way ANOVA, Dunnett's test).

Article Snippet: CleanCap Firefly luciferase (FLuc) mRNA (5‐moU) was purchased from Hongene Biotech.

Techniques: Labeling, Standard Deviation

Journal: Advanced Healthcare Materials

Article Title: CORE: Cholesterol Altered Lipid Nanoparticles for Splenic Expression of mRNA Payloads

doi: 10.1002/adhm.202505862

Figure Lengend Snippet: (a) Schematic representation of endosomal escape quantification via confocal microscopy. (b) Representative images and PCC quantification of CORE LNP taken via confocal microscopy where DC 2.4 cells were stained for nucleus (blue), lysosome (green) and dosed with CORE LNPs encapsulated with Cy‐5 FLuc mRNA (red). Scale bars 50 µm. (c) Schematic representation of calcein leakage assay evaluating the proton sponge effect on endosomal escape. (d) Representative confocal images of DC 2.4 cells treated with Calcein +/‐ bafilomycin A 1 followed by CORE LNPs encapsulating FLuc mRNA. Scale bars 50 µm. (e) Quantification of geometric mean fluorescence intensity (gMFI) of GFP expression after treatment of CORE LNPs encapsulating GFP mRNA treated with or without bafilomycin A 1 . (All data represented as the mean ± standard deviation, n = 4, * p <0.05 as compared to SM‐102 LNP treatment group using one‐way ANOVA, Dunnett's test).

Article Snippet: CleanCap Firefly luciferase (FLuc) mRNA (5‐moU) was purchased from Hongene Biotech.

Techniques: Confocal Microscopy, Staining, Fluorescence, Expressing, Standard Deviation

Journal: Advanced Healthcare Materials

Article Title: CORE: Cholesterol Altered Lipid Nanoparticles for Splenic Expression of mRNA Payloads

doi: 10.1002/adhm.202505862

Figure Lengend Snippet: (A) Biodistribution imaging of lead CORE LNP formulations after IV administration. (B) Determination of organ biodistribution for lead CORE LNP formulations via FLuc expression. (C) Quantification of luminescence within the spleen of lead CORE LNP formulations. (D) ALT, AST, ALP, CREAT, and BUN quantification within the blood after 24 h treatment of lead CORE LNP formulations. (E) Histological evaluation of the liver, lung, and spleen after treatment with C2:F13 compared to naked mRNA and SM‐102 LNP. (All data represented as the mean ± standard deviation, n = 3, ns p >0.05, * p <0.05 as compared to naked mRNA treatment group using one‐way ANOVA, Dunnett's test).

Article Snippet: CleanCap Firefly luciferase (FLuc) mRNA (5‐moU) was purchased from Hongene Biotech.

Techniques: Imaging, Expressing, Standard Deviation