This dime-sized chip transforms cells from one type to another with a small electrical pulse – creating a non-invasive, instantaneous way to repair injured tissue.
Scientists across the field of regenerative medicine are seeking novel ways to convert human cells from one kind to another. By activating different genes within a cell’s DNA, doctors can transform or augment a cell’s function to make it more useful for treating a patient’s injuries or ailments.
Current gene therapies offer targeted approaches for treating diseases such as leukemia; however, these are often invasive procedures, accompanied by major risks and side effects (such as fever and inflammation).
A nanotechnology solution developed by researchers at The Ohio State University is offering a non-invasive alternative in the form of a chip that sits on the surface of the skin. It is the fastest “reprogramming” method to date, capable of shooting genetic code directly into a cell in a fraction of a second.
The innovation loads genetic code — or targeted, cell-changing proteins — to a fingernail-sized chip that is then placed on a patient’s skin. Once the chip is activated by a small electrical current, it instantly begins reprogramming the cells beneath the surface, transforming skin cells into other useful cells necessary for care or life-saving treatment.
In tests on mice, the nanotechnology-based chip was first encoded with the DNA, RNA, or plasma molecules necessary to convert the skin cells into vascular cells. After being placed on the mice’s skin like a stamp, the researchers applied an electrical pulse to the chip to trigger its “biological cargo” to affect the tissue underneath. The zap opens up tiny pores on the cell membranes, through which the cell-transforming genes can enter.
The mice tested had severely damaged legs with little blood flow circulation. Within one week after the chip-based procedure, new vessels were born; in the second week, blood circulation was restored and the injured limbs were saved; and within three weeks, the mice were healed.
In their 4+ years of working on the technology, the researchers also conducted successful blood flow restoration experiments on pigs.
Human trials have yet to begin, but the research is a major breakthrough for emergency medicine. Since the “tissue nano-transfection” (TNT) treatment begins working immediately — and can be carried out without access to a lab or hospital — it could help save lives on the battlefield, after car crashes, or in any other situation where time is a crucial factor.
Many researchers have made advances in this area: for example, the FDA recently approved a leukemia treatment that uses patients’ genetically-altered immune cells to fight the disease.
But existing gene therapies are highly personalized, and the techniques for conducting them involve invasive cell harvesting procedures and lab-based (in vitro) manipulation of the cells. With the leukemia treatment, for example, doctors harvest stem cells and place them in petri dishes, inject genes into those cells while they are outside of the body, and then infuse the modified cells back into patients.
Other gene therapies utilize viral vectors in a similar manner. (Viral vectors are viruses that are stripped of their disease-causing genes and engineered in the lab to carry good genes into a cell.)
Both the stem cell and viral vector approaches come with side effects like fever or inflammation, and pose the risk of causing harmful gene mutations.
Because the TNT procedure utilizes a silicon-based chip that behaves like a miniaturized syringe, it bypasses the need to manipulate cells externally in a lab, instead allowing the process to happen within the body under the guidance of its own immune system.
This means that if the treatment were approved for use in humans, patients wouldn’t need to take immunosuppression (or antirejection) drugs to ensure gene therapies were effective, as they currently must do with the leukemia treatment and other therapies.
TNT also has the potential to be much faster, simpler, and more effective than existing approaches to gene therapy. In the study, first author Daniel Gallego-Perez found that the TNT technique worked with up to 98% effectiveness.
And while it’s far from risk-proof, the small size of the chip — and its immediate activation by a single electrical pulse — means it could become far more accessible and cost-effective than lab-based approaches to gene therapy.
“This process only takes less than a second and is non-invasive, and then you’re off. The chip does not stay with you, and the reprogramming of the cell starts,” said Chandan Sen, PhD.
In addition to the vascular cell experiment, the Ohio State researchers also used the chip to grow and harvest brain cells on the skin of mice that had experienced strokes. They were then able to implant the new nerve cells into the mice’s brains, enabling them to recover in just a few weeks — and leading the researchers to see potential applications for their technology in treating Alzheimer’s and other neurological diseases.
Though the study focused mainly on converting skin cells into other cell types (such as vascular cells or brain cells), the researchers say TNT works for any type of tissue — meaning it could be used to rapidly repair various organs, blood vessels, and nerves.
The Ohio State team continues to refine the TNT technology and associated procedure, but see few barriers to testing their non-invasive procedure in humans in the near future. They hope to start clinical trials next year.
The original article “Topical tissue nano-transfection mediates non-viral stroma reprogramming and rescue” was published in the journal Nature Nanotechnology. Full information is available here.
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