Molecular therapy. Nucleic acidsJan 26, 2026

Improved delivery of genetic material to brain cells after injury using targeted nanoparticles

mRNA Technology Weekly Brief ↗PubMed ↗DOI ↗

Updated Feb 1, 2026

Abstract

The optimal time for delivering lipid nanoparticles (LNPs) carrying mRNA to the injured brain is 24 hours post-injury.

Traumatic brain injury (TBI) results in significant nervous tissue loss and long-term neurological deficits.
Lipid nanoparticles can access the affected nervous tissue due to a temporary disruption of the blood-brain barrier following TBI.
Transfection primarily occurs in astrocytes and endothelial cells, with minimal effects observed in neurons.
Functionalizing LNPs with the peptide RVG increases neuronal transfection by 6.4 times compared to untargeted LNPs.
These findings suggest specific delivery timelines and strategies for enhancing gene delivery to neurons in the injured brain.

Simplified

The consequence of traumatic brain injury (TBI) is significant loss of nervous tissue that leads to long-term neurological deficits. Nucleic acid payloads offer potential treatments that can address the complex pathophysiology that unfolds after injury. TBI causes a transient disruption of the blood-brain barrier, allowing access of systemically administered nanoparticles to the affected nervous tissue. In this work, we evaluated the dosing window post-injury in which lipid nanoparticles (LNPs) carrying mRNA can access and transfect the injured brain after systemic administration and identified 24 h post-injury as a delivery time that achieves both LNP access and transfection activity. We observed that transfected cell types were majorly astrocytes and endothelial cells with no appreciable transfection of neurons. To increase neuronal transfection, we functionalized LNPs with the peptide RVG and were able to increase the proportion of neurons transfected 6.4-fold over untargeted LNPs. These results identify timelines in which LNPs can access the injured brain parenchyma to mediate gene expression and strategies to achieve neuron-specific gene delivery.

Full Text

We can’t show the full text here under this license.

View Full Text ↗

Funding

Competing interests

The authors declare no competing interests.

PubMed

Improved delivery of genetic material to brain cells after injury using targeted nanoparticles

Abstract

Full Text

Funding

Competing interests

You found one interesting study. We’ll send the next 7.

What Lands in Your Inbox Each Week:

Recent issues from the mrna technology brief

Abstract

Full Text

Funding

Competing interests

Related papers

You found one interesting study. We’ll send the next 7.

What Lands in Your Inbox Each Week:

Recent issues from the mrna technology brief