LNP-CRISPR is a delivery mechanism for Luc-mRNA. The LNP consists of either Luc or Cas9 mRNA/sgRNA, and it has a chemical structure. The same mice were examined multiple times. The total data is plotted as a single line per mouse. Credit: DOI: 10.1038/s41467-021-26714-w
Many intractable diseases are the result of a genetic abnormality. New treatments for patients are promised by genome editing technology. Getting the technology to the cells that need the correction is a major challenge. A new study led by CiRA Junior Associate Professor Akitsu Hotta and in collaboration with the T-CiRA Joint Research Program shows how the use of lipid nanoparticles can be used to treat Duchenne muscular dystrophy in mice.
The impact of genome editing technology was solidified last year when the discoverers of CRISPR-Cas9 won the chemistry prize. Most media attention is on its medical potential, despite the fact that it can be applied to agriculture and livestock for more robust crops. Researchers think they can cure many diseases with the use of the CRISPR-Cas9.
Oligonucleotide drugs are available for DMD, but they have short-term effects and have to be treated weekly. Hotta said that the effects of theCas9 are long lasting.
Muscular Dystrophy causes progressive muscle atrophy throughout the body. Patients usually show symptoms such as falling easily and being unable to run before school age, and are usually on a respirator before they are grown up.
Multiple injections are important for a disease like DMD because it is necessary to target a broad range of muscles. The delivery systems that use nonpathogenic viruses to deliver CRISPR-Cas9 are currently investigated.
These reactions can be prevented by conjugates. The name of the particles suggests they are less than 0.1 m in diameter and made up of lipids that change their properties in response to acidity. This feature allows them to stay intact outside the cell, but once inside they can release their content, such as CRISPR-Cas9 which can be used to correct a genetic flaw. The utility of levitating particles for genome editing therapy is still being investigated. Hotta has been working with genome editing technology to deliver it to the cell.
The study reported a novel lipid nanoparticle that targets muscle cells in mice.
The study shows that the effect on muscle lasted beyond one year, unlike the effects on mice, who had their effects diminish after a few months.
The effects were visible even when delivering the particles with multiple injections, whereas the delivery of the virus failed to have an effect after the second injection. In addition, the therapeutic benefit of the nanoparticles was seen on multiple muscle tissues.
"CRISPR-Cas9 disappeared from the body within a few days," Hotta said. The risk of off-target genome editing is minimal, but the effects last a long time.
Eriya Kenjo and her team have shown that the low immunity of LNP allows repeated administrations of CRISPR-Cas9 in mice. There is a DOI titled: 10.1038/s41467-021-26714-w.
Nature Communications is a journal.
The news about genome editing in multiple muscles was retrieved fromphys.org on December 9, 2021.
The document is copyrighted. Any fair dealing for the purpose of private study or research cannot be reproduced without written permission. The content is not intended to be used for anything other than information purposes.
