Researchers who work with tiny drug carriers often called lipid nanoparticles have developed a brand new variety of material able to reaching the lungs and the eyes, a crucial step toward genetic therapy for hereditary conditions like cystic fibrosis and inherited vision loss.
Findings of the study led by Gaurav Sahay and Yulia Eygeris of the Oregon State University College of Pharmacy and Renee Ryals of Oregon Health & Science University were published today within the Proceedings of the National Academy of Sciences.
Unlike other varieties of lipid nanoparticles that are likely to accumulate within the liver, those on this study, based on the compound thiophene, are capable of navigate their option to the tissues of the lungs and retina, where they deliver their therapeutic payload. The researchers confer with these latest lipids as Thio-lipids.
The collaboration demonstrated, through the use of animal models, the potential of using Thio-lipids in lipid nanoparticles to deliver messenger RNA, the technology underpinning COVID-19 vaccines, to combat genetic blindness and pulmonary disease.
“These nanoparticles stuffed with fatty lipids can encapsulate genetic medicines like mRNA and CRISPR-Cas9 gene editors, which could be used to treat and even cure rare genetic diseases,” said Eygeris, a senior research associate at OSU. “Chemical structures of the lipids determine how potent are the lipid nanoparticles and which organ they will reach from the bloodstream.”
Lipids are organic compounds containing fatty tails and are present in many natural oils and waxes, and nanoparticles are tiny pieces of fabric ranging in size from one- to 100-billionths of a meter. Messenger RNA delivers instructions to cells for making a specific protein.
With the coronavirus vaccines, the mRNA carried by the lipid nanoparticles instructs cells to make a harmless piece of the virus’ spike protein, which triggers an immune response from the body.
As a therapy for vision impairment resulting from inherited retinal degeneration, the mRNA would instruct cells within the retina — which don’t work right due to a genetic mutation — to fabricate the proteins needed for sight. Inherited retinal degeneration, commonly abbreviated to IRD, encompasses a bunch of disorders of various severity and prevalence that affect one out of each few thousand people worldwide.
An example of a genetic pulmonary condition is cystic fibrosis, a progressive disorder that ends in persistent lung infection and affects 30,000 people within the U.S., with about 1,000 latest cases identified yearly.
One faulty gene — the cystic fibrosis transmembrane conductance regulator, or CFTR — causes the disease, which is characterised by lung dehydration and mucus buildup that blocks the airway.
The thiophene-based lipid nanoparticle study, which involved mice and non-human primates, stems from a $3.2 million grant to Sahay and Ryals from the National Eye Institute. The grant’s purpose is addressing limitations related to the present primary technique of delivery for gene editing: a variety of virus often called adeno-associated virus, or AAV.
“AAV has limited packaging capability in comparison with lipid nanoparticles and it may prompt an immune system response,” said Sahay, a professor of pharmaceutical sciences. “It also doesn’t do fantastically well in continuing to specific the enzymes the editing tool uses as molecular scissors to make cuts within the DNA to be edited.”
Sahay calls the Thio-lipid findings “highly encouraging” but says more studies are needed, including research on the lipids’ long-term impact on retinal health.
“But we expect our results function a proof of concept and we’ll proceed to explore Thio-lipids in potential treatments of pulmonary and retinal genetic diseases,” he said.
Along with the National Eye Institute, funding and research support were provided by the Oregon National Primate Research Center and the Casey Eye Institute.
