| Using nanotechnology that enabled mRNA-based COVID-19 vaccines, a new approach to gene therapy may improve how physicians treat inherited forms of blindness. | |
| A collaborative team of researchers with Oregon Health & Science University and Oregon State University have developed an approach that uses lipid nanoparticles — tiny, lab-made balls of fat — to deliver strands of messenger ribonucleic acid, or mRNA, inside the eye. To treat blindness, the mRNA will be designed to create proteins that edit vision-harming gene mutations. | |
| In a study published in Science Advances (“Peptide-guided lipid nanoparticles deliver mRNA to the neural retina of rodents and nonhuman primates”), the team demonstrates how its lipid nanoparticle delivery system targets light-sensitive cells in the eye, called photoreceptors, in both mice and nonhuman primates. The system’s nanoparticles are coated with a peptide that the researchers identified as being attracted to photoreceptors. | |
| “Our peptide is like a zip code, and the lipid nanoparticles are similar to an envelope that sends gene therapy in the mail,” explained the study’s corresponding author, Gaurav Sahay, Ph.D., an associate professor in the OSU College of Pharmacy who also has a joint research appointment at the OHSU Casey Eye Institute. “The peptide ensures mRNA is precisely delivered to photoreceptors — cells that we haven’t been able to target with lipid nanoparticles until now.” | |
| “More than 250 genetic mutations have been linked to inherited retinal diseases, but only one has an approved gene therapy,” added study co-author Renee Ryals, Ph.D., an assistant professor of ophthalmology in the OHSU School of Medicine and a scientist at the OHSU Casey Eye Institute. “Improving the technologies used for gene therapy can provide more treatment options to prevent blindness. Our study’s findings show that lipid nanoparticles could help us do just that.” |
| In 2017, the Food and Drug Administration approved the first gene therapy to treat an inherited form of blindness. Many patients have experienced improved vision and have been spared blindness after receiving the therapy, which is sold under the brand name Luxturna. It uses a modified version of the adeno-associated virus, or AAV, to deliver gene-revising molecules. | |
| Today’s gene therapies largely rely on AAV, but it has some limitations. The virus is relatively small and can’t physically contain gene-editing machinery for some complex mutations. And AAV-based gene therapy can only deliver DNA, which results in the continual creation of gene-editing molecules that may lead to unintended genetic edits. | |
| Lipid nanoparticles are a promising alternative because they don’t have size constraints like AAV. Additionally, lipid nanoparticles can deliver mRNA, which only keeps gene-editing machinery active for a short period of time, so could prevent off-target edits. The potential of lipid nanoparticles was further proved by the success of mRNA-based COVID-19 vaccines, which also use lipid nanoparticles to deliver mRNA. They also were the first vaccines to be authorized for COVID-19 in the United States, thanks to the speed and volume at which they can be manufactured. | |
| In this study, Sahay, Ryals and colleagues demonstrated that a peptide-covered lipid nanoparticle shell can be directed toward photoreceptor cells in the retina, tissue in the back of the eye that enables sight. As a first proof of concept, mRNA with instructions to make green fluorescent protein was placed inside nanoparticles. | |
| After injecting this nanoparticle-based gene therapy model into the eyes of mice and nonhuman primates, the research team used a variety of imaging techniques to examine the treated eyes. The animals’ retinal tissue glowed green, illustrating that the lipid nanoparticle shell reached photoreceptors and that the mRNA it delivered successfully entered the retina and created green fluorescent protein. This research marks the first time that lipid nanoparticles are known to have targeted photoreceptors in a nonhuman primate. | |
| The scientists are currently working on follow-up research to quantify how much of the green fluorescent protein is expressed in animal retinal models. They’re also working to develop a therapy with mRNA that carries the code for gene-editing molecules. |
News
New book from NanoappsMedical Inc – Molecular Manufacturing: The Future of Nanomedicine
This book explores the revolutionary potential of atomically precise manufacturing technologies to transform global healthcare, as well as practically every other sector across society. This forward-thinking volume examines how envisaged Factory@Home systems might enable the cost-effective [...]
A Virus Designed in the Lab Could Help Defeat Antibiotic Resistance
Scientists can now design bacteria-killing viruses from DNA, opening a faster path to fighting superbugs. Bacteriophages have been used as treatments for bacterial infections for more than a century. Interest in these viruses is rising [...]
Sleep Deprivation Triggers a Strange Brain Cleanup
When you don’t sleep enough, your brain may clean itself at the exact moment you need it to think. Most people recognize the sensation. After a night of inadequate sleep, staying focused becomes harder [...]
Lab-grown corticospinal neurons offer new models for ALS and spinal injuries
Researchers have developed a way to grow a highly specialized subset of brain nerve cells that are involved in motor neuron disease and damaged in spinal injuries. Their study, published today in eLife as the final [...]
Urgent warning over deadly ‘brain swelling’ virus amid fears it could spread globally
Airports across Asia have been put on high alert after India confirmed two cases of the deadly Nipah virus in the state of West Bengal over the past month. Thailand, Nepal and Vietnam are among the [...]
This Vaccine Stops Bird Flu Before It Reaches the Lungs
A new nasal spray vaccine could stop bird flu at the door — blocking infection, reducing spread, and helping head off the next pandemic. Since first appearing in the United States in 2014, H5N1 [...]
These two viruses may become the next public health threats, scientists say
Two emerging pathogens with animal origins—influenza D virus and canine coronavirus—have so far been quietly flying under the radar, but researchers warn conditions are ripe for the viruses to spread more widely among humans. [...]
COVID-19 viral fragments shown to target and kill specific immune cells
COVID-19 viral fragments shown to target and kill specific immune cells in UCLA-led study Clues about extreme cases and omicron’s effects come from a cross-disciplinary international research team New research shows that after the [...]
Smaller Than a Grain of Salt: Engineers Create the World’s Tiniest Wireless Brain Implant
A salt-grain-sized neural implant can record and transmit brain activity wirelessly for extended periods. Researchers at Cornell University, working with collaborators, have created an extremely small neural implant that can sit on a grain of [...]
Scientists Develop a New Way To See Inside the Human Body Using 3D Color Imaging
A newly developed imaging method blends ultrasound and photoacoustics to capture both tissue structure and blood-vessel function in 3D. By blending two powerful imaging methods, researchers from Caltech and USC have developed a new way to [...]
Brain waves could help paralyzed patients move again
People with spinal cord injuries often lose the ability to move their arms or legs. In many cases, the nerves in the limbs remain healthy, and the brain continues to function normally. The loss of [...]
Scientists Discover a New “Cleanup Hub” Inside the Human Brain
A newly identified lymphatic drainage pathway along the middle meningeal artery reveals how the human brain clears waste. How does the brain clear away waste? This task is handled by the brain’s lymphatic drainage [...]
New Drug Slashes Dangerous Blood Fats by Nearly 40% in First Human Trial
Scientists have found a way to fine-tune a central fat-control pathway in the liver, reducing harmful blood triglycerides while preserving beneficial cholesterol functions. When we eat, the body turns surplus calories into molecules called [...]
A Simple Brain Scan May Help Restore Movement After Paralysis
A brain cap and smart algorithms may one day help paralyzed patients turn thought into movement—no surgery required. People with spinal cord injuries often experience partial or complete loss of movement in their arms [...]
Plant Discovery Could Transform How Medicines Are Made
Scientists have uncovered an unexpected way plants make powerful chemicals, revealing hidden biological connections that could transform how medicines are discovered and produced. Plants produce protective chemicals called alkaloids as part of their natural [...]
Scientists Develop IV Therapy That Repairs the Brain After Stroke
New nanomaterial passes the blood-brain barrier to reduce damaging inflammation after the most common form of stroke. When someone experiences a stroke, doctors must quickly restore blood flow to the brain to prevent death. [...]
