Nature Review: Nebulized Inhalation of mRNA Vaccine

To quote Philip J.

This is a paper published in the journal Nature Biomedical Engineering in September 2021, entitled "Optimizing the delivery of aerosolized therapeutic messenger RNA from lipid nanoparticles to the lungs"

Research methods

Researchers have developed an iterative screening method based on live clustering (an iterative screening method based on live clustering)

The workflow is based on the definition of different chemical features, and each feature acts as an axis in the n-dimensional chemical space

These characteristics include the amount of polyethylene glycol (PEG) added to the lipid nanoparticles, the molecular structure of the lipid-polyethylene glycol, the charge of the phospholipid, and the presence or absence of cholesterol

This design is based on the oligomeric lipid co-linked compound 7C1, and defines 6 extreme groups with different molar ratios, components and charges, and each extreme group contains 8-12 lipid nanoparticles

Research result

These nanoparticles can pass through the nebulization reaction in the body while detecting the delivery efficiency of mRNA

Using this workflow, the authors discovered that PEG-lipid molecules, rather than cholesterol and auxiliary lipids, are the key to the formation of stable 7c1-based lipid nanoparticles

In addition, the combination of cationic auxiliary lipids and high mole percentages increased the delivery of mRNA after nebulization, indicating that the chemical properties of nanoparticles play a more important role in nebulization delivery than particle size

Based on these design rules, a new type of nanoparticle containing high polyPEG lipids and cationic auxiliary lipids was designed for lung delivery, called Nebulized Lung Delivery 1 (NLD1)

NLD1 can effectively deliver mRNA encoding the therapeutic antibody FI6, which binds to hemagglutinin to neutralize influenza viruses of different subtypes

NLD1 aerosol pretreatment can save the lives of mice vaccinated with H1N1 influenza virus

James E.

Summarize

The continuous mutation of SARS-CoV-2 puts forward higher requirements for continuous prevention and control

Traditional mRNA vaccines are injected intramuscularly, which puts forward higher requirements on dosage form stability, storage, transportation, and side-effect monitoring

It also limits the supply of vaccines in underdeveloped areas, which is a dead end for disease prevention and control
.

In contrast, aerosol inhalation of mRNA vaccines can increase the convenience of vaccine use, act on the upper respiratory tract, reduce the incidence of systemic adverse reactions, increase the vaccination rate in underdeveloped areas, and help eliminate the new coronavirus globally
.

However, aerosol inhalation also has its own unique technical requirements, such as stability under the action of aerosol shear and the effectiveness of messenger RNA delivery
.

Scientists from Georgia Institute of Technology and Emory University invented the LNP formula for lung-specific delivery of mRNA vaccines: high PEG lipids and cationic auxiliary lipids, laying the foundation for the development of mRNA atomized vaccines
.

Melissa P.
Lokugamage et al, Optimization of lipid nanoparticles for the delivery of nebulized therapeutic mRNA to the lungs, Nat Biomed Eng.
2021 Sep;5(9):1059-1068.

Christine Horejs, Nebulized lipid nanoparticles, Nat Rev Mater.
2021 Oct 18; 1.
doi: 10.
1038/s41578-021-00392-y.

Eygeris Y, Gupta M, Kim J, Sahay G.
Chemistry of Lipid Nanoparticles for RNA Delivery.
Acc Chem Res.
2021 Dec 1.
doi: 10.
1021/acs.
accounts.
1c00544.

Nature Biomedical Engineering: Nebulized Inhalation of mRNA Vaccine