Poly(aspartic Acid)-Based Polymeric Nanoparticle for Local and Systemic MRNA Delivery

Overview

Journal Mol Pharm

Publisher American Chemical Society

Specialty Pharmacology

Date 2022 Nov 21

PMID 36409995

Authors

Youngrong Park

Abraham S Moses

Ananiya A Demessie

Prem Singh

Hyelim Lee

Tetiana Korzun

Olena R Taratula

Adam W G Alani

Oleh Taratula

Affiliations

Soon will be listed here.

Abstract

Recently, therapeutics based on mRNA (mRNA) have attracted significant interest for vaccines, cancer immunotherapy, and gene editing. However, the lack of biocompatible vehicles capable of delivering mRNA to the target tissue and efficiently expressing the encoded proteins impedes the development of mRNA-based therapies for a variety of diseases. Herein, we report mRNA-loaded polymeric nanoparticles based on diethylenetriamine-substituted poly(aspartic acid) that induce protein expression in the lungs and muscles following intravenous and intramuscular injections, respectively. Animal studies revealed that the amount of polyethylene glycol (PEG) on the nanoparticle surface affects the translation of the delivered mRNA into the encoded protein in the target tissue. After systemic administration, only mRNA-loaded nanoparticles modified with PEG at a molar ratio of 1:1 (PEG/polymer) induce protein expression in the lungs. In contrast, protein expression was detected only following intramuscular injection of mRNA-loaded nanoparticles with a PEG/polymer ratio of 10:1. These findings suggest that the PEG density on the surface of poly(aspartic acid)-based nanoparticles should be optimized for different delivery routes depending on the purpose of the mRNA treatment.

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