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Related Experiment Video

Updated: Jan 12, 2026

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

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

Published on: February 1, 2019

Virus-Inspired mRNA Delivery Vehicle Enabled by a Multilayered Nucleic Acid Nanocapsule.

Suman Pal¹, Divya Singla¹, Rachelle C Canete¹

¹Department of Chemistry, University of Connecticut, 55 North Eagleville Rd, Storrs, Connecticut 06269, United States.

|November 5, 2025

Summary

We developed a novel nanocapsule formulation to improve messenger RNA (mRNA) stability and delivery. This virus-inspired system enhances mRNA shelf life and enables targeted delivery for potential clinical applications.

Keywords:

aptamer enzyme-responsive intracellular delivery mRNA nanocarrier

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Published on: March 31, 2021

Area of Science:

Biotechnology
Nanomedicine
Drug Delivery Systems

Background:

Chemical instability of messenger RNA (mRNA) hinders its clinical use, posing challenges in storage, handling, and patient delivery.
Existing mRNA delivery methods face limitations in stability and targeted cellular uptake.

Purpose of the Study:

To develop a novel nanocapsule formulation for enhanced mRNA stability and targeted delivery.
To address limitations in mRNA storage, handling, and cellular expression.

Main Methods:

A multilayered delivery carrier was designed, featuring a liposomal core stabilized by a metal-organic framework and encapsulated within a nucleic acid nanocapsule.
The formulation incorporates pH and enzyme-specific triggers for controlled mRNA release, mimicking viral delivery mechanisms.
In vitro and in vivo studies were conducted to evaluate mRNA stability, cellular delivery, and therapeutic efficacy.

Main Results:

The nanocapsule formulation demonstrated sustained mRNA expression at room temperature for approximately 14 days and maintained mRNA structural integrity for over 100 days at -20 °C.
Efficient mRNA delivery to the cytosol was achieved using pH and enzyme-specific triggers in vitro and in vivo.
Therapeutic efficacy was shown in an avian influenza model, and homogeneous protein expression was observed in a tumor microenvironment using aptamer-mediated targeting.

Conclusions:

The developed liposomal metal-organic framework-nucleic acid nanocapsule system significantly enhances mRNA stability and shelf life.
This formulation enables targeted, efficient mRNA delivery to specific cell receptors, overcoming key limitations for clinical translation.
The system offers a promising approach for advancing mRNA-based therapeutics.