Researchers have developed LNPs that can precisely deliver mRNA to lung tissue. The therapy of mRNA delivered by LNPs significantly reduced the disease burden of lymphangioleiomyomatosis in animal models.

1. Biopharma PEG https://www.biochempeg.com
New Progress In Lipid Nanoparticles
Technology
Lipid nanoparticles (LNPs) are delivery vehicles for currently two widely used
mRNA COVID-19 vaccines. It has also shown good results in delivering genetic
information to the liver. However, precise delivery of packaged "goods" into tissues other
than the liver remains a challenge. In a recent paper published recently in the
Proceedings of the National Academy of Sciences (PNAS), Dr. Qiaobing Xu's group in the
Department of Bioengineering at Tufts University, along with partners at Harvard
University and the University of Massachusetts, have developed LNPs that can
precisely deliver mRNA to lung tissue. The therapy of mRNA delivered by LNPs
significantly reduced the disease burden of lymphangioleiomyomatosis in animal
models.
It has been shown that by altering the structure of the lipid molecules that make up LNP,
the specificity of their tissue targeting can be changed. By screening the library of lipid

2. Biopharma PEG https://www.biochempeg.com
molecular compounds, Dr. Xu's research group found a series of lipid molecules with
amide bonds at the tail of the lipid molecule, which constitute LNPS that have the
ability to selectively deliver mRNA to the lungs of mice.
Further research found that when lung-targeting LNPs enter the bloodstream, they cause
specific plasma proteins to attach to the surface of LNPs, giving them the ability to target
lung tissue. The researchers identified 14 proteins, including ApoE, albumin, fibrinogen β
and fibrinogen γ, that may contribute to specific absorption of LNPs in the lungs by liquid
chromatography-mass spectrometry.
To further verify the role of LNPs, the researchers used it to deliver mRNA encoding the
normal Tsc2 gene to mice with lymphangioleiomyomatosis due to an inactivating mutation
in the Tsc2 gene. The experimental results show that this LNP can highly efficiently
deliver Tsc2 mRNA into lung cells, restore Tsc2 function, and significantly reduce tumor
burden in mice.
mRNA can be delivered to lung tissue by aerosol inhalation. If administered
intravenously, the drug must avoid liver clearance, continuously interact with lung
endothelial cells, and cross the basement membrane into other types of lung cells. In
contrast, for aerosol inhalation, the drug must diffuse through mucus and avoid
phagocytosis by specialized lung immune cells. Optimizing a systemic mRNA
delivery system differs from optimizing a nebulized drug delivery system due to
differences in delivery barriers. For example, the researchers optimized the delivery of
atomized LNP-mRNA, and the resulting LNP [called Nebulized Lung Delivery 1 (NLD1)]
could deliver significantly more mRNA to the lungs than previously optimized LNPs for
systemic delivery. Therapeutic mRNA encoding the antibody was also delivered to protect
mice from lethal influenza.

3. Biopharma PEG https://www.biochempeg.com
After systemic administration, mRNA can also be delivered to the lungs. A key
finding shows that by adding cationic lipids to common liver-targeting LNPs, two
groups independently demonstrated that these LNPs can be retargeted to the
lungs. The first group of researchers added the permanent cationic lipid DOTAP to LNPs
containing the degradable dendrimer ionizable lipid 5A2-SC8, DLin-MC3-DMA or the
ionizable lipid C12-200, results showed that LNPs containing 50% DOTAP could
effectively modulate lung-specific delivery, and that neither LNP required active targeting
ligands such as antibodies, peptides, or aptamers.
LNP is a highly individually designed nucleic acid delivery vehicle that shows great
potential in mRNA vaccine delivery. In addition, the potential value of LNPs in rare
disease and cancer therapy cannot be ignored. mRNA therapy can help produce
therapeutic proteins to restore the function of damaged tissues or organs.
As a reliable PEG derivatives supplier, Biopharma PEG has been focusing on the
development of a full range of medical applications and technologies for nanocarrier
systems (including various types of nanoparticles, liposomes, micelles, etc.), and offers an
extensive group of PEG-lipid conjugates (DSPE PEG) incorporating various
functionalized PEG terminal, like Biotin, Amine, Carboxylic acid, Azide, Aldehyde, Thiol,
and Hydroxy. We can produce and provide the some PEG products as ingredients used in

4. Biopharma PEG https://www.biochempeg.com
COVID-19 vaccines. For more information, please visit website at PEGs for COVID-19
Vaccines.
References:
[1] Targeting gene therapy directly into the lungs. Retrieved February 23, 2022, from
https://medicalxpress.com/news/2022-02-gene-therapy-lungs.html
[2] Qiu et al., (2022). Lung-selective mRNA delivery of synthetic lipid nanoparticles for the treatment of
pulmonary lymphangioleiomyomatosis. PNAS, https://doi.org/10.1073/pnas.2116271119
Related articles:
[1] Lipid Nanoparticles: Key Technology For mRNA Delivery
[2] Lipid Nanoparticles for Drug and Vaccine Delivery
[3] Overview of mRNA-Lipid Nanoparticle COVID-19 Vaccines
[4] Liposomes vs. Lipid Nanoparticles: Which Is Best for Drug Delivery?