Researchers on the Icahn Faculty of Drugs at Mount Sinai have developed a lipid nanoparticle system able to delivering messenger RNA (mRNA) to the mind by way of intravenous injection, bypassing the blood-brain barrier. The examine demonstrates the potential of this know-how for treating situations similar to drug dependancy, mind most cancers, amyotrophic lateral sclerosis, and Alzheimer’s illness.
The blood-brain barrier restricts the passage of many substances, together with therapeutic brokers, into the mind. Earlier analysis at Mount Sinai launched a platform for delivering massive biomolecules, similar to proteins and oligonucleotides, into the central nervous system. This examine takes a special strategy by utilizing particularly designed lipid nanoparticles to move mRNA throughout the barrier.
Delivering mRNA to the mind may allow the manufacturing of therapeutic proteins by mind cells, doubtlessly stopping or treating illnesses by enhancing protecting mechanisms, changing faulty proteins, or decreasing dangerous ones.
Our examine exhibits that these blood-brain barrier-crossing lipid nanoparticles (BLNPs) can safely and effectively ship mRNA into the mind. This might open up alternatives to make use of mRNA-based therapies for quite a lot of neurological and psychiatric problems.
Yizhou Dong, Examine Co-Corresponding Creator and Professor, Immunology and Immunotherapy, The Mount Sinai Hospital
Dong is a member of the Icahn Genomics Institute and the Marc and Jennifer Lipschultz Precision Immunology Institute on the Icahn Faculty of Drugs at Mount Sinai.
To reinforce the power of lipid nanoparticles to cross the blood-brain barrier, the analysis group designed and examined a library of lipids. Structural and useful analyses recognized a lead formulation, MK16 BLNP, which demonstrated considerably greater mRNA supply effectivity in comparison with FDA-approved lipid nanoparticles.
The researchers report that this technique makes use of the blood-brain barrier’s endogenous transport mechanisms, together with γ-secretase- and caveolae-mediated transcytosis, to facilitate nanoparticle switch throughout the barrier.
The BLNP platform has proven potential for medical utility by efficiently delivering therapeutic mRNAs to the mind in mouse fashions of illness.
Dr. Dong says, “Our lipid nanoparticle system represents an vital step within the effort to develop mRNA-based remedies for central nervous system problems. The examine gives proof of idea that such an strategy is viable and could possibly be tailored for a spread of illnesses the place gene remedy or mRNA therapeutics may play a job.”
The researchers emphasize that additional research, together with FDA-compliant toxicology assessments, are mandatory to guage long-term security and efficacy. Future analysis will concentrate on advancing the know-how towards medical utility.
Our findings spotlight the potential of lipid nanoparticles in overcoming one of many main challenges in treating mind illnesses. We’re very excited to proceed evaluating this novel platform for broader therapeutic functions.
Eric J. Nestler, Examine Co-Corresponding Senior Creator, The Mount Sinai Hospital
J. Nestler is the Director of The Friedman Mind Institute, Dean for Tutorial Affairs, and Nash Household Professor within the Nash Household Division of Neuroscience on the Icahn Faculty of Drugs at Mount Sinai. He additionally serves as Chief Scientific Officer of the Mount Sinai Well being System.
Co-authors of the examine embody 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 analysis was supported by the Nationwide Institute of Normal Medical Sciences, the Nationwide Institute on Drug Abuse, and Biogen.
Journal Reference:
Wang, C., et al. (2025) Blood–brain-barrier-crossing lipid nanoparticles for mRNA supply to the central nervous system. Nature Supplies. doi.org/10.1038/s41563-024-02114-5.
