Editing Faulty Genes Before Birth? Biomedical Tool May Help, Study Reveals - Video

A new study shows that a biomedical tool can successfully deliver genetic material to edit faulty genes in developing fetal brain cells. A complex transportation system with a revolutionary delivery method. The scientists found a way to deliver messenger RNA (mRNA) to cells that will be translated to functional proteins. This delivery method uses a unique lipid nanoparticle (LNP) formulation to carry mRNA. The objective is to introduce or transfect mRNA genetic material into the cells. The mRNA then would translate instructions to build proteins.

In a recent Nature Nanotechnology paper, Wang, Murthy and their team described a new lipid nanoparticle formulation to safely and efficiently deliver mRNA. lipid nanoparticle carrying mRNA need to arrive at the cells, where they will be taken in through a process known as endocytosis. There, the cell breaks the lipid nanoparticle carrier, which allows the mRNA cargo to be released. The study showed that the lipid nanoparticle method is more efficient at mRNA translation, reducing the need for potentially toxic doses.

The researchers injected the lipid nanoparticle with the mRNA into the fetal brain's ventricles in a mouse model. The mRNA translates into CAS9, a protein that works like scissors for gene editing. The produced CAS9 will edit the gene responsible for Angelman syndrome. The study showed that the lipid nanoparticle tool was very efficient in delivering the mRNA that translated into CAS 9.

Using tracers, the researchers could see all the neurons that were edited inside the brain. Their study showed that the nanoparticles were taken up by the brain’s developing neural stem and progenitor cells. The nanoparticles led to gene edits in 30% of the brain stem cells in the mouse model. In the study, as the fetal development continued, the stem cells proliferated and migrated to form the central nervous system.

Reference: Widespread Gene Editing in the Brain via In Utero Delivery of mRNA Using Acid-Degradable Lipid Nanoparticles. Kewa Gao, Hesong Han, Matileen G. Cranick, Sheng Zhao, Shanxiu Xu, Boyan Yin, Hengyue Song, Yibo Hu, Maria T. Clarke, David Wang, Jessica M. Wong, Zehua Zhao, Benjamin W. Burgstone, Diana L. Farmer, Niren Murthy, and Aijun Wang. ACS Nano Article ASAP. DOI: 10.1021/acsnano.4c05169