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Generation of Cationic Nanoliposomes for the Efficient Delivery of In Vitro Transcribed Messenger RNA

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Published on: February 1, 2019

Poly(aspartic acid)-Based Polymeric Nanoparticle for Local and Systemic mRNA Delivery.

Youngrong Park¹, Abraham S Moses¹, Ananiya A Demessie¹

¹Department of Pharmaceutical Sciences, College of Pharmacy, Oregon State University, Portland, Oregon 97239, United States.

Molecular Pharmaceutics

|November 21, 2022

Summary

New polymeric nanoparticles effectively deliver messenger RNA (mRNA) for protein expression in lungs and muscles. Optimizing polyethylene glycol (PEG) density on these nanoparticles is crucial for targeted mRNA delivery and therapeutic outcomes.

Keywords:

PEGylation gene therapy mRNA delivery polymeric nanoparticle systemic delivery

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Published on: August 13, 2021

Area of Science:

Biotechnology
Nanomedicine
Polymer Chemistry

Background:

Messenger RNA (mRNA) therapeutics show promise for vaccines, cancer immunotherapy, and gene editing.
Effective delivery vehicles are needed to overcome challenges in mRNA-based therapies.
Polymeric nanoparticles offer potential for biocompatible mRNA delivery.

Purpose of the Study:

To develop and evaluate mRNA-loaded polymeric nanoparticles for targeted protein expression.
To investigate the role of polyethylene glycol (PEG) density on nanoparticle surface for mRNA delivery.
To determine optimal PEGylation strategies for different administration routes (intravenous and intramuscular).

Main Methods:

Synthesized mRNA-loaded nanoparticles using diethylenetriamine-substituted poly(aspartic acid).
Modified nanoparticles with varying ratios of polyethylene glycol (PEG) to polymer.
Administered nanoparticles intravenously and intramuscularly in animal models.
Assessed protein expression in target tissues (lungs and muscles).

Main Results:

Nanoparticles induced protein expression in lungs after intravenous injection with a 1:1 PEG/polymer ratio.
Protein expression was observed in muscles following intramuscular injection with a 10:1 PEG/polymer ratio.
PEG density significantly impacts mRNA translation efficiency and tissue targeting.

Conclusions:

Diethylenetriamine-substituted poly(aspartic acid) nanoparticles are effective carriers for mRNA delivery.
Surface PEGylation density is a critical factor for achieving tissue-specific protein expression via mRNA.
Tailoring PEG density is essential for optimizing mRNA therapies for different delivery routes and therapeutic goals.