ionizable lipids for mRNA delivery that combines machine learning with advanced combinatorial chemistry tools. Starting from a simple four-component reaction platform, we create a chemically diverse library of 584 ionizable lipids. We screen the mRNA transfection potencies of lipid nanoparticles ...
这些结果表明iPhos类脂可能通过与ionizable amino lipids不同的机制 图2 a, iPLNPs处理IGROV1细胞后的荧光素酶表达热图(50 ng萤火虫荧光素酶(Fluc) mRNA, n = 3个生物学独立的样本)。以10000的相对轻单位(RLU)计算命中率。b,酸性核内体环境中具有不同数量两性离子和尾部的iPhos的典型化学结构。c, iPhos与单...
However, a pivotal component of lipid nanoparticle development that remains a bottleneck is identifying new ionizable lipids. Here we describe an accelerated approach to discovering effective ionizable lipids for mRNA delivery that combines machine learning with advanced combinatorial chemistry tools. ...
Although initially developed for siRNA delivery, multi-tail ionizable lipids can be repurposed for efficient mRNA delivery by optimizing the LNP composition via design of experiment methodologies with significantly reduced workload14,15. For example, the optimized formulation ofC12-200increased mRNA expre...
A library of 24 ionizable lipids was synthesized, formulated into LNPs, and screened for luciferase mRNA delivery to Jurkat cells, revealing seven formulations capable of enhanced mRNA delivery over lipofectamine. The top-performing LNP formulation, C14-4, was selected for CAR mRNA delivery to ...
LNPs are great delivery tools for mRNA, siRNA, and other nucleic acid cargo due to their ability to effectively protect and deliver the cargo. LNPs are primarily formulated with four components (other than the nucleic acid cargo): cationic ionizable lipids, ...
The efficacy of mRNA-based vaccines and therapies relies on lipid nanoparticles (LNPs) as carriers to deliver mRNA into cells. The chemical structure of ionizable lipids (ILs) within LNPs is crucial in determining their delivery efficiency. In this study
Lipid nanoparticles (LNPs) are widely used for nucleic acid delivery but face challenges like limited targeting and accelerated blood clearance (ABC) effect. We design three ionizable oligomers (IOs) that, with polylactide-polyethylene glycol (PLA-PEG),
As a result, lipids with pKa value between 6.2 and 6.5 achieve a balance between the two opposing delivery requirements, improving the resulting functionality. The pKa of clinically-applied Dlin-MC3-DMA was 6.44, and the ED50 (median effective dose for FVII gene silencing in female C57BL/6 ...
The spleen emerges as a pivotal target for mRNA delivery, prompting a continual quest for specialized and efficient lipid nanoparticles (LNPs) designed to enhance spleen-selective transfection efficiency. Here we report imidazole-containing ionizable lipids (IMILs) that demonstrate a pronounced preference...