Journal of controlled release : official journal of the Controlled Release SocietyMar 22, 2025

Using Lipid Nanoparticles to Deliver mRNA for Treating Brain Degenerative Diseases

mRNA Technology Weekly Brief ↗PubMed ↗DOI ↗

Updated Apr 5, 2026

Abstract

Lipid nanoparticles (LNPs) may improve mRNA delivery to the central nervous system (CNS) for treating neurodegenerative diseases.

Neurodegenerative diseases (NDD) involve the progressive loss of neurons and impaired cellular functions.
Messenger RNA (mRNA) can encode proteins that are missing or dysfunctional, potentially halting NDD progression.
Effective delivery of mRNA to the CNS is challenged by the blood-brain barrier (BBB).
Lipid nanoparticles (LNPs) can encapsulate and protect mRNA, enhancing its transfection and delivery to cells.
Strategies for improving mRNA-LNP delivery include non-invasive methods and AI-guided design approaches.
LNP-mediated mRNA delivery could transform treatment options for various neurological disorders.

Simplified

Neurodegenerative diseases (NDD) are characterized by the progressive loss of neurons and the impairment of cellular functions. Messenger RNA (mRNA) has emerged as a promising therapy for treating NDD, as it can encode missing or dysfunctional proteins and anti-inflammatory cytokines or neuroprotective proteins to halt the progression of these diseases. However, effective mRNA delivery to the central nervous system (CNS) remains a significant challenge due to the limited penetration of the blood-brain barrier (BBB). Lipid nanoparticles (LNPs) offer an efficient solution by encapsulating and protecting mRNA, facilitating transfection and intracellular delivery. This review discusses the pathophysiological mechanisms of neurological disorders, including Parkinson's disease (PD), Alzheimer's disease (AD), multiple sclerosis (MS), Huntington's disease (HD), ischemic stroke, spinal cord injury, and Friedreich's ataxia. Additionally, it explores the potential of LNP-mediated mRNA delivery as a therapeutic strategy for these diseases. Various approaches to overcoming BBB-related challenges and enhancing the delivery and efficacy of mRNA-LNPs are discussed, including non-invasive methods with strong potential for clinical translation. With advancements in artificial intelligence (AI)-guided mRNA and LNP design, targeted delivery, gene editing, and CAR-T cell therapy, mRNA-LNPs could significantly transform the treatment landscape for NDD, paving the way for future clinical applications.

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Declaration of competing interest The authors declare no competing financial interest.

PubMed

Using Lipid Nanoparticles to Deliver mRNA for Treating Brain Degenerative Diseases

Abstract

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