A recent study reveals a novel biomedical tool capable of delivering genetic material to edit faulty genes in developing fetal brain cells. Conducted on mice, this technology may halt the progression of genetic neurodevelopmental disorders, such as Angelman syndrome and Rett syndrome, prior to birth.
Senior author Aijun Wang, a professor at UC Davis, emphasizes the potential of this tool to correct genetic anomalies during critical brain development phases. The collaborative study, involving the Wang Lab and the Murthy Lab at UC Berkeley, has been published in ACS Nano.
The innovative delivery system utilizes lipid nanoparticles (LNPs) to transport messenger RNA (mRNA) into cells, which then translates into functional proteins. This approach, which has gained attention through its application in COVID-19 vaccines, aims to address challenges in delivering proteins directly to cells.
In a recent publication in Nature Nanotechnology, the researchers described a new LNP formulation designed for safe and efficient mRNA delivery. These nanoparticles are engineered to degrade within cells, enhancing the release of mRNA where it can be utilized for protein synthesis.
Wang notes that the efficiency of this delivery method is crucial, as low uptake can necessitate higher doses, potentially leading to toxicity. The study demonstrated that the LNP method significantly improves mRNA translation efficiency, reducing the risk of adverse immune responses.
The researchers applied this LNP technology to deliver Cas9 mRNA, an enzyme essential for gene editing, to treat genetic diseases affecting the central nervous system in utero. By injecting LNPs into the fetal brain, they successfully edited the gene associated with Angelman syndrome.
The findings indicate that the LNP tool effectively transfected 30% of brain stem cells in the mouse model, with the potential for these edited cells to proliferate and migrate, offering hope for correcting neurodevelopmental conditions before birth.
Wang's team collaborates with the UC Davis MIND Institute to further explore the application of LNP technology in various neurological disorders, aiming for future trials in larger animal models and, eventually, humans.
The research received funding from multiple institutions, including Shriners Children's and the National Institutes of Health.