A team of researchers working with small-scale drug delivery systems known as lipid nanoparticles has created a novel material that can target the lungs and eyes.
This breakthrough is a significant advancement towards genetic treatments for hereditary diseases such as cystic fibrosis and inherited vision loss.
The study, led by Gaurav Sahay, Yulia Eygeris from the College of Pharmacy at Oregon State University, and Renee Ryals from Oregon Health & Science University, has been published in the Proceedings of the National Academy of Sciences.
This new development is centered around lipid nanoparticles composed of a compound named thiophene, which unlike traditional lipid nanoparticles that mainly accumulate in the liver, have the unique ability to reach the lung and retinal tissues to deliver therapeutic agents. The research team has named these innovative lipids Thio-lipids.
By conducting experiments on animal models, the researchers demonstrated that Thio-lipids can effectively transport messenger RNA, a key element in the COVID-19 vaccines, to address genetic blindness and lung diseases.
Yulia Eygeris, a senior research associate at Oregon State University, explained that these Thio-lipid nanoparticles can encapsulate genetic treatments such as mRNA and CRISPR-Cas9 gene-editing tools. These treatments have the potential to address and possibly cure rare genetic disorders. The chemical makeup of the lipids influences the effectiveness of the nanoparticles and their ability to target specific organs through the bloodstream.
Lipids, which are organic compounds with fatty components, combine with nanoparticles—extremely small materials measuring between one to 100-billionths of a meter—to deliver messenger RNA that instructs cells to produce specific proteins.
For instance, in the case of coronavirus vaccines, the mRNA within the lipid nanoparticles prompts cells to produce a harmless segment of the virus’s spike protein, eliciting an immune response. For inherited retinal degeneration, a condition that impairs vision due to genetic mutations, mRNA would guide retinal cells to produce the necessary proteins for sight.
Cystic fibrosis, a genetic lung disorder affecting around 30,000 people in the U.S. annually, is another condition that could benefit from this technology. It is caused by a mutation in the cystic fibrosis transmembrane conductance regulator gene, leading to lung dehydration and mucus accumulation that obstructs airflow.
The research on thiophene-based lipid nanoparticles, which included studies on mice and non-human primates, aims to overcome the limitations of adeno-associated virus (AAV), the current primary delivery mechanism for gene editing. AAVs have limited capacity and can trigger immune responses, in addition to their inability to sustain long-term enzyme expression needed for DNA editing.
Although Sahay, a professor of pharmaceutical sciences, described the Thio-lipid results as “highly encouraging,” he acknowledged the need for further research on their long-term effects on retinal health. Nonetheless, he views these findings as a proof of concept for continuing to explore Thio-lipids as a treatment for genetic lung and eye diseases.
The study also involved contributions from other researchers at the Oregon State University College of Pharmacy, including Mohit Gupta, Jeonghwan Kim, Antony Jozic, Milan Gautam, Jonas Renner, Dylan Nelson, and Elissa Bloom.
