Nat biotechnol: a novel nano capsule for efficient delivery of cas9 ribonucleic acid protein complex for genome editing in vivo

September 24, 2019 / Bio Valley bio on / -- a new tool for editing genetic codes brings hope for new therapies for genetic diseases, some cancers and even stubborn viral infections However, the typical way to transfer gene therapy to specific tissues of the body can be complex and can lead to disturbing side effects Researchers at the University of Wisconsin Madison solved many of these problems by loading gene editing payloads into customizable microsynthetic nanocapsules Recently, they described the new delivery system in the journal Nature Nanotechnology Photo source: Shaoqin "Sarah" Gong, a biomedical engineering professor and researcher at the UW Madison Institute for discovery at UW Madison, said: "in order to edit genes in cells, editing tools need to be implanted safely and effectively "Her lab specializes in designing and building nanoscale delivery systems for targeted therapy Krishanu Saha, a biomedical engineering professor at the University of Wisconsin Madison and co chair of the steering committee of the National Association of genome editors, said: "editing the wrong tissue in the body after gene therapy injection is a serious problem "The Association received $190 million in funding from the National Institutes of health "If the reproductive organs are inadvertently edited, patients will pass the edited genes on to their children and offspring "Gong said that most genome editing is done through viral vectors It has been billions of years of experience for viruses to invade cells and make new copies of viruses using their own mechanisms In gene therapy, viruses can be modified to carry genome editing mechanisms, rather than carrying their own viral genes into cells Then, the editing mechanism can change the DNA of the cell, for example, correcting a problem in the genetic code that causes or causes the disease "Viral vectors are attractive because they can be very effective, but they are also related to many security issues, including unwanted immune responses," said Gong New cell targets may also require laborious changes in viral vectors, and the manufacture of custom viral vectors may be complex "It's very difficult to customize many viral vectors to deliver to specific cells or tissues in the body," Saha said "Gong's lab wraps the gene therapy payload, a version of crispr-cas9, a gene editing tool designed by Saha lab, on a thin polymer shell to form a capsule about 25 nanometers in diameter The surface of nanocapsules can be decorated with polypeptides and other functional groups, so that nanoparticles can target certain cell types The nanocapsules remain intact outside the cell - in the blood, for example - only when the target cell is triggered by a molecule called glutathione Then, the released payload moves to the nucleus, editing the cell's DNA Due to the short life span of nanocapsules in cell cytoplasm, it is expected to reduce unexpected gene editing The project combines the University of Wisconsin Madison expertise in chemistry, engineering, biology and medicine Bikash R pattnaik, Professor of Pediatrics and Ophthalmology, and Masatoshi Suzuki, Professor of comparative biology, and their team demonstrated gene editing of mouse eyes and skeletal muscles with nanocapsules, respectively Because nanocapsules can be freeze-dried, they can be easily purified, stored and transported as powders, while providing flexibility for dose control Researchers at the Wisconsin Alumni Research Foundation are patenting nanoparticles "The small size, good stability, multifunctional surface modification and high editing efficiency of nanocapsules make them a promising platform for many gene therapies," said Gong "The team's goal is to further optimize the nanocapsules that effectively edit the brain and eyes in ongoing research Reference: Shaoqin Gong et al A biodegradable nanocapsule deliveries a cas9 ribonucleoprotein complex for in vivo genome editing Nature Nanotechnology (2019) DOI https://doi.org/10.1038/s41565-019-0539-2