纳米颗粒单细胞多组学读出技术揭示了细胞异质性会影响脂质纳米颗粒介导的信使 RNA 递呈。
Nanoparticle single-cell multiomic readouts reveal that cell heterogeneity influences lipid nanoparticle-mediated messenger RNA delivery.
机构信息
Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University School of Medicine, Atlanta, GA, USA.
Parker H. Petit Institute for Bioengineering and Biosciences, Georgia Institute of Technology, Atlanta, GA, USA.
出版信息
Nat Nanotechnol. 2022 Aug;17(8):871-879. doi: 10.1038/s41565-022-01146-9. Epub 2022 Jun 30.
Cells that were previously described as homogeneous are composed of subsets with distinct transcriptional states. However, it remains unclear whether this cell heterogeneity influences the efficiency with which lipid nanoparticles (LNPs) deliver messenger RNA therapies in vivo. To test the hypothesis that cell heterogeneity influences LNP-mediated mRNA delivery, we report here a new multiomic nanoparticle delivery system called single-cell nanoparticle targeting-sequencing (SENT-seq). SENT-seq quantifies how dozens of LNPs deliver DNA barcodes and mRNA into cells, the subsequent protein production and the transcriptome, with single-cell resolution. Using SENT-seq, we have identified cell subtypes that exhibit particularly high or low LNP uptake as well as genes associated with those subtypes. The data suggest that cell subsets have distinct responses to LNPs that may affect mRNA therapies.
先前被描述为同质的细胞由具有不同转录状态的亚群组成。然而，目前尚不清楚这种细胞异质性是否会影响脂质纳米颗粒（LNPs）在体内传递信使 RNA 疗法的效率。为了验证细胞异质性会影响 LNP 介导的 mRNA 传递的假设，我们在这里报告了一种新的多组学纳米颗粒传递系统，称为单细胞纳米颗粒靶向测序（SENT-seq）。SENT-seq 定量分析了数十个 LNPs 将 DNA 条形码和 mRNA 递送到细胞中的情况、随后的蛋白质产生情况以及单细胞分辨率下的转录组情况。使用 SENT-seq，我们已经鉴定出表现出特别高或低 LNP 摄取的细胞亚型以及与这些亚型相关的基因。这些数据表明，细胞亚群对 LNPs 有不同的反应，这可能会影响 mRNA 疗法。
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