Single-cell encoded gene silencing for high-throughput combinatorial siRNA screening

Feng Guo, Xianglin Ji, Chuxiao Xiong, Hailiang Sun, Zhenghua Liang, Richard Yan-Do, Baowen Gai, Feng Gao, Linfeng Huang, Zhongping Li, Becki Yi Kuang and Peng Shi ()
Additional contact information
Feng Guo: Kowloon
Xianglin Ji: Kowloon
Chuxiao Xiong: Kowloon
Hailiang Sun: Kowloon
Zhenghua Liang: The Hong Kong University of Science and Technology, Kowloon
Richard Yan-Do: Kowloon
Baowen Gai: Sun Yat-sen University
Feng Gao: Sun Yat-sen University
Linfeng Huang: Duke Kunshan University
Zhongping Li: Shanxi University
Becki Yi Kuang: The Hong Kong University of Science and Technology, Kowloon
Peng Shi: Kowloon

Nature Communications, 2024, vol. 15, issue 1, 1-15

Abstract: Abstract The use of combinatorial siRNAs shows great promise for drug discovery, but the identification of safe and effective siRNA combinations remains challenging. Here, we develop a massively multiplexed technology for systematic screening of siRNA-based cocktail therapeutics. We employ composite micro-carriers that are responsive to near infrared light and magnetic field to achieve photoporation-facilitated siRNA transfection to individual cells. Thus, randomized gene silencing by different siRNA formulations can be performed with high-throughput single-cell-based analyses. For screening anti-cancer siRNA cocktails, we test more than 1300 siRNA combinations for knocking down multiple genes related to tumor growth, discovering effective 3-siRNA formulations with an emphasis on the critical role of inhibiting Cyclin D1 and survivin, along with their complementary targets for synergic efficacy. This approach enables orders of magnitude reduction in time and cost associated with largescale siRNA screening, and resolves key insights to siRNA pharmacology that are not permissive to existing methods.

Date: 2024
References: View references in EconPapers View complete reference list from CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/s41467-024-53419-7 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-53419-7

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-024-53419-7

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().