Scientists of the Icahn Medicine School of Mount Sinai have developed a system of lipid nanoparticles capable of delivering messenger RNA (mRNA) to the brain via intravenous injection, a challenge that has long been limited by the protective nature of the Hémato-Encephalic barrier.
The results, in mouse models and isolated human brain fabrics were published in the online issue of February 17 of Nature materials (10.1038 / S41563-024-02114-5). They demonstrate the potential of this technology to open the way for future treatments for a wide range of conditions such as Alzheimer’s disease, amyotrophic lateral sclerosis, brain cancer and drug addiction.
The blood-brain barrier serves as a protective shield, preventing many substances, including potentially beneficial therapies to harm the brain. While the previous research of Mount Sinai has introduced a platform to transport large biomolecules such as proteins and oligonucleotides in the center nervous systemThis new study focuses on a different approach: using lipid nanoparticles specially designed to transport the mRNA through the barrier.
Bringing mRNA into the brain could allow scientists to indicate brain cells to produce therapeutic proteins that can help treat or prevent diseases by replacing missing proteins, reducing harmful proteins or activating the defenses of body.
Our study shows that these growing lipid nanoparticles of the hemato-encephalic barrier (BLNP) can deliver arnm in the brain. This could open up opportunities to use therapies based on mRNA for a variety of neurological and psychiatric disorders. “”
Yizhou Dong, Phd, co-corners of the main author, Professor of immunology and Immunotherapyand member of Icahn Genomics Institute and the Institute of Immunology of Precision Marc and Jennifer Lipschultz, Icahn School of Medicine in Mount Sinai
The research team has designed and tested a lipid library to optimize their ability to cross the blood-brain barrier. Thanks to a series of structural and functional analyzes, they identified a lead formulation, called MK16 BLNP, which had an effectiveness of administration of arnm significantly higher than the lipid nanoparticles existing by the Food and Drug Administration (FDA ). This system takes advantage of natural transport mechanisms in the blood-brain barrier, including mediated transcytosis by cavities and γ-secretase, to move nanoparticles through the barrier, the researchers said.
In studies using mouse disease models, the BLNP platform has successfully delivered therapeutic brain therapeutic mRNAs, demonstrating its clinical application potential.
“Our system of lipid nanoparticles represents an important step in the effort to develop mRNA -based treatments for central nervous system disorders,” said Dong Dong. “The study provides proof of concept that such an approach is viable and could be adapted to a range of diseases where gene therapy Or the Therapeutics mrnm could play a role. “”
Researchers note that additional studies are necessary to assess long -term safety and efficiency, including toxicology studies in accordance with FDA directives. Future research will focus on refining clinical translation technology.
“Our results highlight the potential of lipid nanoparticles to overcome one of the main challenges in the treatment of brain diseases,” said the main author Eric J. Nestler, MD, PHD, director of the Friedman Brain Institute, Dean of Academic Affairs, and Nash family teacher at the Nash Family Department of Neuroscience at the Icahn Medicine School of Mont Sinai and scientific director of Mount Sinai Health System. “We are very happy to continue to assess this new platform for wider therapeutic applications.”
The document is entitled “Lipid nanoparticles of blood crossing for the barrier for the delivery of mRNA to the central nervous system.”
The authors of the study, listed in the journal, are Chang Wang, Yonger Xue, Tamara Markovic, Haoyuan Li, Siyu Wang, Yichen Zhong, Shi du, Yuebao Zhang, Xucheng Hou, Yang Yu, Zhengwei Liu, Meng Tian, Diana D. Kang, Leiming Wang, Kaiyuan Guo, Dinglingge Cao, Jingyue Yan, Binbin Deng, David W. McComb, Ramon E. Parsons, Angelica M. Minier-Toribio, Leanne M. Holt, Jiayi Pan, Alice Hashemi, Brian H. Kopell, Alexander W. Charney, Eric J. Nestler, Paul C. Peng and Yizhou Dong.
The study was supported by the National Institute of General Medical Sciences (R35GM144117), the National Institute on Drugs Abuse (P01DA047233) and Biogen.
Source:
Journal reference:
Wang, C., et al. (2025). Lipid nanoparticles of cross-bloods crossing for the administration of mRNA with the central nervous system. Nature materials. DOI.org/10.1038/S41563-024-02114-5.