Scientists at the ICAHN Medical School on Mount Sinai have developed a lipid nanopartic system capable of delivering the messenger RNA (mRNA) to the brain through intravenous injection, a challenge that has long been confined to the protective nature of the blood barrier.
Findings, in mice models and isolated human brain tissue, were published in the online issue of February 17th Materials [10.1038/s41563-024-02114-5]. They show the potential of this technology to pave 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, incorporating potentially beneficial therapies-from the achievement of the brain. While previous research from Mount Sinai introduced a platform for the transportation of large biomolecules such as proteins and oligonucleotides to the central nervous system, this new study focuses on a different approach: using specially designed lipid nanoparticles .
Taking mRNA to the brain could allow scientists to guide brain cells to produce therapeutic proteins that can help treat or prevent the disease by replacing missing proteins by reducing harmful or activating the defenses of the body.
Our study shows that these lipid nanoparticles that cross the blood -brain barrier (BLNPS) can safely and effectively deliver the mRNA to the brain. This could open opportunities for use of MRNA -based treatments for a variety of neurological and psychiatric disorders. ”
Yizhou Dong, Phd, Co-athleted senior writer, Professor of Immunology and Immunotherapy and a member of the ICAHN GENOMICS Institute and the Jenschultz Accuracy Institute
The research team designed and examined a lipid library to optimize their ability to cross the blood -brain barrier. Through a series of structural and functional analyzes, they identified a lead synthesis, called MK16 BLNP, which presented significantly higher MRNA delivery effectiveness than existing lipid nanoparticles approved by the Food and Drug Administration (FDA). This system takes advantage of natural transport mechanisms within the blood-brain barrier, including Caveolae-and C-Sekretase mediated to move nanoparticles throughout the barrier, the researchers say.
In studies using disease mouse models, the BLNP platform has successfully handed MRNAS therapeutic to the brain, proving its capabilities for clinical application.
“Our lipid nanopartic system represents an important step in trying to develop MRNA -based treatments for central nervous system disorders,” says Dr. Dong. “The study provides a proof of the concept that such an approach is sustainable and can be adapted for a number of diseases where gene therapy or therapeutic mRNA can play a role.”
Researchers note that additional studies are needed to evaluate long -term safety and efficiency, including toxicology studies in accordance with FDA guidelines. Future research will focus on improving clinical translation technology.
“Our findings highlight the potential of lipid nanoparticles to overcome one of the most important challenges for the treatment of brain diseases,” says senior writer Eric J. Nestler, MD, Director of the Friedman Brain, Dean for Academic Affairs and Professor of the NASH family in the Department of Neuroscience of the NASH family at the ICAHN School of Medicine on Mount Sinai and the head of the Mount Sinai Health System. “We are very excited to continue to evaluate this new platform for wider therapeutic applications.”
The document is entitled “Lipid nanoparticles that cross blood-brain to supply mRNA to the central nervous system”.
The authors of the study, as mentioned in the magazine, 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 Drug Abuse Institute (P01DA047233) and Biogen.
Source:
Magazine report:
Wang, C., et al. (2025). The lipid nanoparticles that cross the blood-brain to supply mRNA to the central nervous system. Materials. Doi.org/10.1038/S41563-024-02114-5.
