5 research outputs found

    Additional file 4: Figure S3. of Enhanced in vitro osteogenic differentiation of human fetal MSCs attached to 3D microcarriers versus harvested from 2D monolayers

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    Kinetics of osteogenic gene expression during osteogenic differentiation of S27 hfMSC in PCL-TCP scaffold cultures. (A) Cultures seeded with 2D monolayer-harvested (2D MNL-harv) and microcarrier-harvested (3D MC-harv) cells, (B) Cultures seeded with microcarrier-harvested (2D MNL-harv) and microcarrier-bound (3D MC-bound) cells. Two-way repeated measures ANOVA with post-hoc Tukey correction was performed between 3D MC-harv, 2D MNL-harv and 3D MC-bound cells using Graphpad, (*p < 0.05 and at least a 2-fold difference in the means). Of the multiple comparisons performed, data representing a single comparison is shown: (A) 3D MC-harv vs 2D MNL-harv, (B) 3D MC-bound vs 2D MNL-harv. (TIFF 544 kb

    Ionizable Lipid Nanoparticles for Therapeutic Base Editing of Congenital Brain Disease

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    Delivery of mRNA-based therapeutics to the perinatal brain holds great potential in treating congenital brain diseases. However, nonviral delivery platforms that facilitate nucleic acid delivery in this environment have yet to be rigorously studied. Here, we screen a diverse library of ionizable lipid nanoparticles (LNPs) via intracerebroventricular (ICV) injection in both fetal and neonatal mice and identify an LNP formulation with greater functional mRNA delivery in the perinatal brain than an FDA-approved industry standard LNP. Following in vitro optimization of the top-performing LNP (C3 LNP) for codelivery of an adenine base editing platform, we improve the biochemical phenotype of a lysosomal storage disease in the neonatal mouse brain, exhibit proof-of-principle mRNA brain transfection in vivo in a fetal nonhuman primate model, and demonstrate the translational potential of C3 LNPs ex vivo in human patient-derived brain tissues. These LNPs may provide a clinically translatable platform for in utero and postnatal mRNA therapies including gene editing in the brain
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