Scientists from the Oregon State University (OSU) School of Pharmacy in the United States have demonstrated the possibility of using lipid nanoparticles and messenger RNA in animals, the technology on which COVID-19 vaccines are basedto treat blindness associated with a rare genetic disease.
The researchers developed nanoparticles capable of penetrating the neural retina and administer mRNA to the photoreceptor cells whose proper functioning makes vision possible, as published in the journal ‘Science Advances’.
The study, led by OSU Associate Professor of Pharmaceutical Sciences Gaurav Sahay, Oregon State doctoral student Marco Herrera-Barrera, and Oregon Health & Science University Assistant Professor of Limitation of Ophthalmology Renee Ryals, has passed the The main reason for using lipid nanoparticles (NPLs) to transport genetic material for vision therapy purposes: getting it to the back of the eye, where the retina is located.
Lipids are fatty acids and similar organic compounds, including many naturally occurring oils and waxes. Nanoparticles are tiny fragments of material that range in size from one to one hundred billionth of a meter. Messenger RNA instructs cells to make a certain protein.
The model with the coronavirus
In the case of coronavirus vaccines, the mRNA carried by PCNLs instructs cells to make a harmless fragment of the virus’s spike protein, triggering an immune response from the body. In the treatment of vision disorders due to hereditary retinal degeneration (DHR), the mRNA would instruct photoreceptor cells, defective due to a genetic mutation, to manufacture the proteins necessary for vision.
The DHR encompasses a group of disorders of varying severity and prevalence that occur in one in thousands of people worldwide.
mice and primates
The scientists demonstrated, in research with mice and non-human primates, that peptide-equipped NPLs were able to cross the barriers of the eye and reach the neural retina, where the light is transformed into electrical signals that the brain converts into images.
«We identified a new set of peptides capable of reaching the back of the eye,» explains Sahay. «We use these peptides as zip codes to transport nanoparticles with genetic material to the desired address within the eye.»
«The peptides we have discovered can be used as targeting ligands directly conjugated to silencing RNAs, small molecules for therapeutics, or as imaging probes,» adds Herrera-Barrera.
Sahay and Ryals have received a grant of 3.2 million dollars (almost 3 million euros) from the National Eye Institute of the United States to continue studying the promise of lipid nanoparticles in the treatment of hereditary blindness. They will lead research into using lipid nanoparticles to deliver a gene-editing tool that could remove defective genes from photoreceptor cells and replace them with properly functioning genes.
The goal of the research is to develop solutions to the limitations associated with the current main means of delivery for gene editing: a type of virus known as adeno-associated virus (AAV).
«AAV has limited packaging ability compared to NPLs and can elicit an immune system response,» Sahay explains. «In addition, it doesn’t express very well the enzymes that the editing tool uses like molecular scissors to cut DNA.» what is going to be editedR. use we we have learn to now about the NPL to development an improved system of Administration of editors genetics».