Nanotechnology

Drug delivery system overcomes circulatory obstacles that prevent gene therapy from reaching its target

Graphical summary. Credit: Cell (2024). DOI: 10.1016/j.cell.2024.07.023

Harnessing the remarkable ability of viruses to deliver gene therapy across previously circulatory obstacles is at the heart of a University of Alberta-led discovery that promises to reinvigorate the field of genetic medicine.

John Lewis, an oncologist in the School of Medicine and Dentistry and lead author of the study describing this advance, explains that the liver is the main obstacle to safely and effectively distributing therapeutic drugs throughout the body. .

“Current delivery systems are good in theory, but they have a major flaw in targeting the liver,” says Lewis, who is also a member of the Northern Alberta Cancer Institute. “You can make them work in a dish, but as soon as you inject the drug into a person, these techniques often fail.”

“If you’re treating a brain disease or a lung disease, you don’t want the drug to reach the liver. You need a solution that targets the right tissues and cells.”

Lewis said that current lipid nanoparticle (LNP) drug delivery technologies are loaded with components such as cholesterol, which are destined to accumulate in the liver, and that there are many potential applications, such as gene therapy, mRNA vaccines, and gene editing technologies. He explains that this is the reason why many proven genetic medicines have been created. It is expelled from the body before reaching its target.

To explore delivery mechanisms that bypass the liver, Lewis worked for decades with Roy Duncan, a virologist at Dalhousie University known for discovering a protein made by a unique fusogenic orthoreovirus that has the ability to fuse cells. We have cooperated over the years. The results of this study will be published in the journal Cell.

By combining this fusion protein with modified lipid nanoparticles designed to transport therapeutic substances, the research team was able to design a proteolipid vehicle platform known as FAST-PLV. This platform allows treatments to bypass the liver and more effectively target areas such as the brain and lungs. It is less toxic than current delivery platforms and also avoids immune system stimulation. This means repeated dosing is possible, which is important in addressing diseases that require continuous or multiple interventions.

To demonstrate that the new platform could deliver genetic payloads without being intercepted by the liver, Lewis’ team used a protein that aids muscle development, often associated with a particularly muscular breed of cattle known as the Belgian Blue. Developed gene therapy. When this platform was introduced into mice, the genetically engineered mice not only bypassed the liver but also had twice the muscle mass of untreated mice. This approach may be useful in debilitating conditions such as frailty and sarcopenia.

“This platform is a plug-and-play solution, so anyone developing new gene editing technologies or treatments for diseases other than the liver can use this platform to create medicines,” Lewis says. .

First on the agenda for Lewis and his team is a new coronavirus vaccine that is scheduled to enter Phase 2 clinical trials.

The development schedule for these additional treatments is also ambitious. Lewis said Stargardt disease trials could begin within the next two years, but research into cancer treatments is already underway.

“We were originally focused on cancer treatment and aimed to use genetics as an alternative to traditional chemotherapy,” he says.

Lewis also envisions treatments for diseases such as muscular dystrophy, cystic fibrosis, Alzheimer’s disease and Parkinson’s disease in the near future.

“Perhaps this technology could be used to treat all the terrible and debilitating rare diseases that affect children born with these mutations,” he says.

Lewis added that the platform’s impact extends far beyond just advancements in delivery technology. These represent a paradigm shift in the possibility of curing genetic diseases and could transform the lives of millions of people suffering from previously untreatable diseases.

“We are just at the beginning of what this technology can accomplish. With the right focus and collaboration, the sky is the limit.”

Further information: Douglas W. Brown et al, Safe and effective in vivo delivery of DNA and RNA using proteolipid vehicles, Cell (2024). DOI: 10.1016/j.cell.2024.07.023

Magazine information: Cell

Provided by University of Alberta

Citation: Drug delivery systems overcome circulatory obstacles that prevent gene therapies from reaching their targets (October 23, 2024) https://phys.org/news/2024-10-drug-delivery-circulatory- Retrieved October 23, 2024 from roadblock-gene.html

This document is subject to copyright. No part may be reproduced without written permission, except in fair dealing for personal study or research purposes. Content is provided for informational purposes only.

Related Articles

Leave a Reply

Your email address will not be published. Required fields are marked *

Back to top button