Breaking Barriers in Drug Delivery with Better Lipid Nanoparticles

Researchers from Lawrence Berkeley National Laboratory (Berkeley Lab) and Genentech, a member of the Roche Group, have collaborated to develop an efficient lipid nanoparticle (LNP) delivery system for therapeutic agents.

LNPs are tiny spherical pouches made of fatty molecules that encapsulate drugs and deliver them to target cells. The success of LNPs in the Pfizer and Moderna mRNA COVID-19 vaccines has brought attention to their potential as a delivery system for other vaccines and therapeutic treatments.

The team, led by co-lead authors Chun-Wan Yen from Genentech and Greg Hura and Michal Hammel from Berkeley Lab, has been studying how to optimize LNP structure and properties for several years. They recently published a paper in ACS Nano detailing their high-throughput workflow that allows for rapid production and characterization of LNPs. The study also demonstrates the correlation between LNP structure and the activity of its contents, using an anti-sense oligonucleotide (ASO) as a test case.

ASOs are short RNA or DNA sequences that block gene expression and can be used to treat diseases caused by faulty proteins. The researchers found that LNPs with ordered, closely-packed internal structures showed better gene silencing activity in human neurons associated with a degenerative disease, compared to LNPs with a more disordered structure.

To generate a large dataset for analysis, the team developed a high-throughput method for LNP production, while Berkeley Lab’s advanced light source facility performed small-angle X-ray scattering (SAXS) to determine LNP structure and stability. The combined techniques allow for rapid screening and optimization of potential LNPs.

The researchers plan to expand their studies to investigate LNPs with different cargo types and their interactions with various target cells. The goal is to enhance understanding of LNPs and further improve their applications in drug delivery.

The study was supported by the Department of Energy Office of Science and the Office of Biological and Environmental Research.

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