新しいスクリーニング技術により、mRNA治療の迅速化と改善が期待される(New Screening Technique Could Accelerate and Improve mRNA Therapies)

2022-06-30 ジョージア工科大学

<関連情報>

• https://bme.gatech.edu/news/all-one-sequencing-key-improving-lipid-nanoparticle-effectiveness
• https://www.nature.com/articles/s41565-022-01146-9

ナノ粒子のシングルセルマルチオミクスリードアウトにより、細胞の不均一性が脂質ナノ粒子を介したメッセンジャーRNA送達に影響することが明らかに。 Nanoparticle single-cell multiomic readouts reveal that cell heterogeneity influences lipid nanoparticle-mediated messenger RNA delivery

Curtis Dobrowolski,Kalina Paunovska,Elisa Schrader Echeverri,David Loughrey,Alejandro J. Da Silva Sanchez,Huanzhen Ni,Marine Z. C. Hatit,Melissa P. Lokugamage,Yanina Kuzminich,Hannah E. Peck,Philip J. Santangelo & James E. Dahlman
Nature Nanotechnology  Published:30 June 2022
DOI:https://doi.org/10.1038/s41565-022-01146-9

Abstract

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.