Researchers developing an new tools for editing genetic code offer; hope for new treatments for inherited diseases, some cancers, and even stubborn viral infections. But the typical method for delivering gene therapies; to specific tissues in the body can be complicating and may cause troubling side effects. So study addressing many of those problems by packing a gene-editing payload into a tiny customizable, synthetic nanocapsule.
Editing the wrong tissue in the body after injecting gene therapies is of grave concern; but also a UW-Madison biomedical engineering professor and steering committee co-chair for a nationwide consortium on genome editing with $190 million in support from the National Institutes of Health. If reproductive organs are inadvertently edited; then the patient would pass on the gene edits to their children and every subsequent generation.
Editing genetic code
Most genome editing is done with viral vectors, according to Gong. Viruses have billions of years of experience invading cells and co-opting the cell’s own machinery to make new copies of the virus. In gene therapy, viruses can be altering to carry genome-editing machinery rather than their own viral genes into cells. The editing machinery can then alter the cell’s DNA to, say, correct a problem in the genetic code that causes or contributes to disease.
Viral vectors are attractive because they can be very efficient, but they are also associating with a number of safety concerns including undesirable immune responses. New cell targeting can also require laborious alterations of viral vectors; and manufacturing tailoring viral vectors can be complicating. Gene therapy payload namely, a version of the gene-editing tool CRISPR-Cas9 with guide RNA designed in Saha’s lab with a thin polymer shell, resulting in a capsule about 25 nanometers in diameter.
Thin polymer shell
The surface of the nanocapsule can be decorating with functional groups; such as peptides which give the nanoparticles the ability to target certain cell types. The nanocapsule stays intact outside cells in the bloodstream, for example only to fall apart inside the target cell when triggered by a molecule called glutathione. The freed payload then moves to the nucleus to edit the cell’s DNA.
Because the nanocapsules can be freeze-dry, they can be conveniently purifying; stored, and transported as a powder, while providing flexibility for dosage control. The researchers, with the Wisconsin Alumni Research Foundation, have a patent pending on the nanoparticles. The small size, superior stability, versatility in surface modification; and high editing efficiency of the nanocapsules make them a promising platform for many types of gene therapies.