PNAS: Novel nanoparticles target gene therapy directly to the lungs

Researchers at Tufts University School of Engineering are pinpointing drug delivery

Even before LNP delivery made its splashy debut with a COVID-19 vaccine, Qiaobing Xu and his team are applying the technology to a wider range of diseases with treatments that target specific tissues and organs, which could help reduce the risk of infection in other healthy parts of the body.

In a study published in the Proceedings of the National Academy of Sciences, a team led by Tufts University researcher Qiaobing Xu found that Tsc2 occurs in individuals with a rare disease called lymphangioleiomyomatosis (LAM).

"This effect is very impressive," said the study's corresponding author, Professor Qiaobing Xu, professor of biomedical engineering at Tufts University.

This remarkable achievement builds on earlier groundbreaking research in which the research team created LNPs that carry gene-editing packages that enter the immune system or liver cells, or even wear Cross the blood-brain barrier to reach specific areas of the brain

"We were able to show that we could deliver gene editing to the lung, but it occurred in the liver, in which case the size and composition of the gene editing kit may have affected the ability of the LNPs to selectively target the lung

You might wonder how they transfer lnp to the lungs

By testing many combinations of heads, tails and connections, as well as other components of LNPs, such as cholesterol or polyethylene glycol, the researchers were able to target not only the brain or immune system, but also the spleen, liver, and even specific cell types

The two main lungs targeting LNPs, 306-N16B and 113-N16B, have linkers containing nitrogen atoms, which appear to be critical for targeting the lungs

"We found that the molecules that make up LNPs acquire proteins and other molecules from plasma, and it is the 'top' of this substance that interacts with the target tissue, organ or cell," Xu said

By analyzing the plasma proteins attached to the LNPs, the researchers narrowed down to 14 proteins that may contribute to adhesion and absorption into the lungs, including ApoE, albumin, fibrinogen beta and fibrinogen gamma

"Finding the right targeted combination is really a process of trial and error, but we can certainly find it in the time frame needed to discover treatments for multiple diseases

article title

Lung-selective mRNA delivery of synthetic lipid nanoparticles for the treatment of pulmonary lymphangioleiomyomatosis