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University of California, San Diego

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Small, Nov 05 2024, | https://doi.org/10.1002/smll.202405806 PEGylated Multimeric RNA Nanoparticles for siRNA Delivery in Traumatic Brain Injury

Sangwoo Han ¹, Woojung Yoo ^1,2, Olivia Carton ¹, Jinmyoung Joo ^2,3,4,5, Ester J. Kwon ^1,5,6

¹Department of Bioengineering, University of California San Diego, La Jolla, CA, 92093, USA.

²Department of Biomedical Engineering, Ulsan National Institute of Science and Technology (UNIST), Ulsan, 44919, Republic of Korea.

³Graduate School of Health Science and Technology, Ulsan National Institute of Science and Technology (UNIST), Ulsan, 44919, Republic of Korea.

⁴Center for Genomic Integrity, Institute for Basic Science, Ulsan, 44919, Republic of Korea.

⁵Materials Research Science and Engineering Center, University of California San Diego, La Jolla, CA, 92093, USA.

⁶Sanford Consortium for Regenerative Medicine, La Jolla, CA, 92037, USA.

Corresponding Author : Ester J. Kwon

Abstract

Traumatic brain injury (TBI) impacts millions of people globally, however currently there are no approved therapeutics that address long-term brain health. In order to create a technology that is relevant for siRNA delivery in TBI after systemic administration, sub-100 nm nanoparticles with rolling circle transcription (RCT) are synthesized and isolated in order improve payload delivery into the injured brain. Unlike conventional RCT-based RNA particles, in this method, sub-100 nm RNA nanoparticles (RNPs) are isolated. To enhance RNP pharmacokinetics, RNPs are synthesized with modified bases in order to graft polyethylene glycol (PEG) to the RNPs. PEGylated RNPs (PEG-RNPs) do not significantly impact their knockdown activity in vitro and lead to longer blood half-life after systemic administration and greater accumulation into the injured brain in a mouse model of TBI. In order to demonstrate RNA interference (RNAi) activity of RNPs, knockdown of the inflammatory cytokine TNF-α in injured brain tissue after systemic administration of RNPs in a mouse model of TBI is demonstrated. In summary, small sub-100 nm multimeric RNA nanoparticles are synthesized and isolated that can be modified using accessible chemistry in order to create a technology suitable for systemic RNAi therapy for TBI.

논문정보

형식Research article
게재일2024년 11월 (BRIC 등록일 2024-11-07)
연구진국외 연구진
분야 바이오·의료융합 > 바이오센싱 및 나노바이오물질

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