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Updated: Jun 8, 2025

Delivery of Therapeutic siRNA to the CNS Using Cationic and Anionic Liposomes

Delivery of Therapeutic siRNA to the CNS Using Cationic and Anionic Liposomes

Published on: July 23, 2016

PEGylated Multimeric RNA Nanoparticles for siRNA Delivery in Traumatic Brain Injury.

Sangwoo Han¹, Woojung Yoo^1,2, Olivia Carton¹

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

Small (Weinheim an Der Bergstrasse, Germany)

|November 5, 2024

Summary

This summary is machine-generated.

New RNA nanoparticles (RNPs) show promise for treating traumatic brain injury (TBI). These sub-100 nm PEGylated RNPs effectively deliver therapeutic RNA to the injured brain after systemic administration.

Keywords:

RNA nanoparticle blood half‐life polyethylene glycol rolling circle transcription traumatic brain injury

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Area of Science:

Biotechnology
Nanomedicine
Neuroscience

Background:

Traumatic brain injury (TBI) affects millions globally, with no current therapeutics for long-term brain health.
Effective delivery of therapeutics to the injured brain remains a significant challenge.

Purpose of the Study:

To develop sub-100 nm RNA nanoparticles (RNPs) for systemic siRNA delivery in TBI.
To enhance RNP pharmacokinetics and brain accumulation for improved therapeutic efficacy.

Main Methods:

Synthesis and isolation of sub-100 nm RNPs using rolling circle transcription (RCT).
Grafting polyethylene glycol (PEG) to RNPs via modified bases to create PEG-RNPs.
Evaluation of PEG-RNPs in vitro knockdown activity and in vivo TBI mouse model.

Main Results:

PEGylated RNPs (PEG-RNPs) demonstrated no significant impact on in vitro knockdown activity.
Systemic administration of PEG-RNPs resulted in longer blood half-life and increased accumulation in the injured brain.
Demonstrated RNA interference (RNAi) activity by knocking down TNF-α in TBI mouse brain tissue.

Conclusions:

Small, sub-100 nm multimeric RNA nanoparticles can be synthesized and isolated for TBI therapy.
Accessible chemical modifications enable the creation of a technology suitable for systemic RNAi therapy for TBI.