Mother Nature provides new gene therapy strategy to reverse disease – Health Europa
By daniellenierenberg
Though the research was intended as a proof of concept, the experimental gene therapy slowed tumour growth and prolonged survival in mice with gliomas, which constitute about 80% of malignant brain tumours in humans.
The technique takes advantage of exosomes, fluid-filled sacs that cells release as a way to communicate with other cells.
The research was carried out by scientists at the Ohio State University and published in the journal Nature Biomedical Engineering.
While exosomes are gaining ground as biologically friendly carriers of therapeutic materials because there are a lot of them and they dont prompt an immune response the trick with gene therapy is finding a way to fit those comparatively large genetic instructions inside their tiny bodies on a scale that will have a therapeutic effect.
This new method relies on patented technology that prompts donated human cells such as adult stem cells to spit out millions of exosomes that, after being collected and purified, function as nanocarriers containing a drug.
When they are injected into the bloodstream, they know exactly where in the body to find their target even if its in the brain.
Senior study author L. James Lee, professor emeritus of chemical and biomolecular engineering at Ohio State University, said: Think of them like Christmas gifts: the gift is inside a wrapped container that is postage paid and ready to go. This is a Mother Nature-induced therapeutic nanoparticle.
In 2017, Lee and colleagues made waves with news of a regenerative medicine discovery called tissue nanotransfection (TNT). The technique uses a nanotechnology-based chip to deliver biological cargo directly into skin, an action that converts adult cells into any cell type of interest for treatment within a patients own body.
By looking further into the mechanism behind TNTs success, scientists in Lees lab discovered that exosomes were the secret to delivering regenerative goods to tissue far below the skins surface.
The scientists placed about one million donated cells on a nano-engineered silicon wafer and used an electrical stimulus to inject synthetic DNA into the donor cells. As a result of this DNA force-feeding, as Lee described it, the cells need to eject unwanted material as part of DNA transcribed messenger RNA and repair holes that have been poked in their membranes.
The electrical stimulation had a bonus effect of a thousand-fold increase of therapeutic genes in a large number of exosomes released by the cells, a sign that the technology is scalable to produce enough nanoparticles for use in humans.
Essential to any gene therapy is knowing what genes need to be delivered to fix a medical problem. For this work, the researchers chose to test the results on glioma brain tumours by delivering a gene called PTEN, a cancer-suppressor gene. Mutations of PTEN that turn off that suppression role can allow cancer cells to grow unchecked.
For Lee, founder of Ohio States Center for Affordable Nanoengineering of Polymeric Biomedical Devices, producing the gene is the easy part. The synthetic DNA force-fed to donor cells is copied into a new molecule consisting of messenger RNA, which contains the instructions needed to produce a specific protein. Each exosome bubble containing messenger RNA is transformed into a nanoparticle ready for transport, with no blood-brain barrier to worry about.
The testing in mice showed the labelled exosomes were far more likely to travel to the brain tumours and slow their growth compared to substances used as controls.
Because of exosomes safe access to the brain, Lee said, this drug-delivery system has promise for future applications in neurological diseases such as Alzheimers and Parkinsons disease.
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Mother Nature provides new gene therapy strategy to reverse disease - Health Europa
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