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Related Experiment Video

Updated: May 10, 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

Manufacturing mRNA-Loaded Lipid Nanoparticles with Precise Size and Morphology Control.

Cedric Devos¹, Aniket Udepurkar¹, Peter Sagmeister¹

¹Department of Chemical Engineering, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, Massachusetts 02139, United States.

|September 15, 2025

Summary

This study introduces a new method for producing lipid nanoparticles (LNPs) for nucleic acid therapeutics. The technique offers precise control over LNP size and morphology, enhancing transfection efficacy.

Keywords:

formulation lipid nanoparticle mRNA mixing morphology nucleic acid size

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Area of Science:

Biotechnology
Materials Science
Pharmaceutical Sciences

Background:

Lipid nanoparticles (LNPs) are crucial for delivering nucleic acid therapeutics.
Current LNP production methods often oversimplify self-assembly into a single mixing step, limiting control over LNP properties.
The relationship between process inputs and LNP characteristics remains poorly understood in conventional manufacturing.

Purpose of the Study:

To develop a method for producing mRNA-loaded LNPs with independent and predictive control over size and morphology.
To decouple LNP particle design from mixing parameters and formulation adjustments.
To enable the rational engineering of LNPs with specific, desired properties.

Main Methods:

Utilized mixing under high fusogenicity conditions by modulating solvent composition.
Employed timed post-injection of an aqueous buffer to kinetically arrest LNPs.
Demonstrated the method using benchmark LNP formulations in an impinging jet mixer.

Main Results:

Achieved independent and predictive control over LNP size and morphology.
Produced LNPs with up to an 8-fold increase in in vitro transfection efficacy compared to conventional methods.
Maintained other essential quality attributes without compromise.

Conclusions:

The presented method allows for rational engineering of LNPs with defined properties.
This approach facilitates enhanced quality control, predictive modeling, and rational process translation for LNP manufacturing.
The findings pave the way for more effective nucleic acid therapeutics delivery systems.