Tiny capsules offer alternative to viral delivery of gene therapy

Biology
Tiny capsules offer alternative to viral delivery of gene therapy
A graphic description of the nanocapsule delivery system. Credit: UW-Madison

More

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 complicated and may cause troubling side effects.

Researchers at the University of Wisconsin-Madison have addressed many of those problems by packing a gene-editing payload into a tiny customizable, synthetic . They described the and its cargo today (Sept. 9, 2019) in the journal Nature Nanotechnology.

“In order to edit a gene in a cell, the editing tool needs to be delivered inside the cell safely and efficiently,” says Shaoqin “Sarah” Gong, a professor of biomedical engineering and investigator at the Wisconsin Institute for Discovery at UW-Madison. Her lab specializes in designing and building nanoscale delivery systems for targeted therapy.

“Editing the wrong tissue in the body after injecting gene therapies is of grave concern,” says Krishanu Saha, 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 are inadvertently edited, then the patient would pass on the gene edits to their children and every subsequent generation.”

Most genome editing is done with , 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 altered to carry genome-editing machinery rather than their own viral 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 associated with a number of safety concerns including undesirable immune responses,” says Gong.

New cell targets can also require laborious alterations of viral vectors, and manufacturing tailored viral vectors can be complicated.

“It is very difficult—if not impossible—to customize many viral vectors for delivery to a specific cell or tissue in the body,” Saha says.

Gong’s lab coated a 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. The surface of the nanocapsule can be decorated with functional groups such as peptides which give the nanoparticles the ability to target certain .

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. The nanocapsules are expected to reduce unplanned genetic edits due to their short lifespan inside a cell’s cytoplasm.

This project is a collaboration combining UW-Madison expertise in chemistry, engineering, biology and medicine. Pediatrics and ophthalmology professor Bikash R. Pattnaik and comparative biosciences professor Masatoshi Suzuki and their teams worked to demonstrate gene editing in mouse eyes and skeletal muscles, respectively, using the nanocapsules.

Because the nanocapsules can be freeze-dried, they can be conveniently purified, 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 , superior stability, versatility in surface modification, and high editing efficiency of the nanocapsules make them a promising platform for many types of gene therapies,” says Gong.

The team aims to further optimize the nanocapsules in ongoing research for efficient editing in the brain and the eye.




Explore further

Researchers redefine the footprint of viral vector gene therapy


More information:
A biodegradable nanocapsule delivers a Cas9 ribonucleoprotein complex for in vivo genome editing, Nature Nanotechnology (2019). DOI: 10.1038/s41565-019-0539-2 , https://nature.com/articles/s41565-019-0539-2

Citation:
Tiny capsules offer alternative to viral delivery of gene therapy (2019, September 9)
retrieved 10 September 2019
from https://phys.org/news/2019-09-tiny-capsules-alternative-viral-delivery.html

This document is subject to copyright. Apart from any fair dealing for the purpose of private study or research, no
part may be reproduced without the written permission. The content is provided for information purposes only.

Articles You May Like

Nanostructures help to reduce the adhesion of bacteria
Experiment measures velocity in 3-D
Are California blackouts the new normal for the state?
Discovered: Unknown yellow colors from antiquity
Computer-Assisted Judging Is Being Tested at Gymnastics World Championships