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Efficient Transfection of In vitro Transcribed mRNA in Cultured Cells Using Peptide-Poloxamine Nanoparticles

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Non-viral mRNA delivery to the lungs.

Lauren Healy¹, Breanna Y Seto¹, Haissi Cui¹

¹Department of Chemistry, University of Toronto, Toronto, Ontario, M5S 3H6, Canada. bw.li@utoronto.ca.

Biomaterials Science

|April 23, 2025

Summary

Advancing messenger RNA (mRNA) therapies for lung diseases requires overcoming delivery barriers. This review explores novel nanoparticle strategies to improve targeted mRNA delivery to the lungs, enhancing treatment potential.

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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

Area of Science:

Biotechnology
Nanomedicine
Respiratory Medicine

Background:

Messenger RNA (mRNA) therapeutics show great promise, accelerated by COVID-19 vaccine success.
Non-viral delivery systems are crucial for mRNA therapies but face challenges in lung targeting.
Biological barriers like pulmonary mucus and off-target accumulation impede effective lung delivery.

Purpose of the Study:

To review current strategies for enhancing lung-targeted mRNA delivery.
To identify key challenges in delivering mRNA therapeutics to the lungs.
To provide a roadmap for advancing clinical translation of lung mRNA therapies.

Main Methods:

Focus on lipid nanoparticles (LNPs), polymeric nanoparticles, lipid-polymer hybrids, and peptide/protein conjugates.
Discuss bioinspired design principles for nanoparticles.
Examine nanoparticle reformulation techniques to improve lung delivery.

Main Results:

Emerging nanoparticle strategies show potential to overcome lung delivery barriers.
Bioinspired design and reformulation can enhance nanoparticle stability and targeting.
Targeted delivery is key to reducing off-target accumulation, particularly in the liver.

Conclusions:

Overcoming lung-specific delivery challenges is essential for realizing mRNA therapy potential in respiratory diseases.
Advanced nanoparticle formulations offer promising solutions for targeted lung delivery.
Further research in bioinspired design and reformulation will accelerate clinical translation of lung mRNA therapies.