Related Experiment Video
Updated: Jun 26, 2026
08:29
Generation of Cationic Nanoliposomes for the Efficient Delivery of In Vitro Transcribed Messenger RNA
Published on: February 1, 2019
10.1K
Lipid Nanoparticles Deliver mRNA to the Brain after an Intracerebral Injection.
Jan Tuma1,2, Yu-Ju Chen1, Michael G Collins1
1The Department of Cellular and Integrative Physiology, The University of Texas Health Science Center at San Antonio, San Antonio, Texas 78229, United States.
Biochemistry
|September 20, 2023
Summary
Lipid nanoparticles effectively deliver mRNA therapeutics to the adult mouse brain, targeting multiple cell types. This breakthrough offers new hope for treating neurological disorders.
Area of Science:
- Neuroscience
- Biotechnology
- Gene Therapy
Background:
- Neurological disorders are debilitating conditions lacking effective disease-modifying treatments.
- Current therapies are primarily palliative, highlighting the need for novel therapeutic strategies.
- Messenger RNA (mRNA) therapeutics show promise but face delivery challenges, especially to the brain.
Purpose of the Study:
- To evaluate the efficacy of MC3-based lipid nanoparticles (LNPs) for delivering mRNA into the adult mouse brain.
- To assess the transfection and gene-editing efficiency of LNP-delivered mRNA in key brain regions.
- To determine the cell-type specificity of LNP-mediated mRNA delivery in the brain.
Main Methods:
- Direct intracerebral injection of MC3-based LNPs carrying Cre mRNA or Cas9 mRNA/Ai9 sgRNA into adult Ai9 mice.
- Analysis of LNP distribution and transfection efficiency in the striatum and hippocampus.
- Assessment of gene editing efficiency using Cas9 mRNA/Ai9 sgRNA in targeted brain regions.
- Cell-type analysis to identify transfected cells, including neurons, astrocytes, and microglia.
Main Results:
- MC3-based LNPs successfully delivered mRNA throughout the striatum and hippocampus.
- High transfection efficiencies were observed: ~52% in the striatum and ~49% in the hippocampus for Cre mRNA.
- Demonstrated gene editing capabilities with ~7% efficiency in the striatum and ~3% in the hippocampus for Cas9 mRNA/Ai9 sgRNA.
- Confirmed LNP-mediated delivery to neurons, astrocytes, and microglia.
Conclusions:
- MC3-based LNPs are an effective vector for mRNA delivery to the adult brain.
- LNP-mediated mRNA delivery shows significant potential for treating complex neurological disorders.
- This approach opens new avenues for developing targeted therapies for brain diseases.
Related Concept Videos
02:22Regulated mRNA Transport
In eukaryotes, transcription and translation are compartmentalized; an mRNA is first synthesized in the nucleus and then selectively transported to the cytoplasm for protein synthesis. Before transport, a pre-mRNA undergoes several steps of post-transcriptional modifications including splicing, 5' capping, and the addition of a poly-adenine tail. Various proteins bind to the pre-mRNA during these modifications. The mRNA transport takes place with the help of multiple proteins playing specific...
01:25Nucleic Acid Structure
The pentose sugar in DNA is deoxyribose, while in RNA the pentose sugar is ribose. The difference between the sugars is the presence of the hydroxyl group on the ribose's second carbon and a hydrogen on the deoxyribose's second carbon. The phosphate residue attaches to the hydroxyl group of the 5′ carbon of one sugar and the hydroxyl group of the 3′ carbon of the sugar of the next nucleotide, which forms a 5′ to 3′ phosphodiester linkage.
DNA Structure
DNA has a double-helix structure. The...
DNA Structure
DNA has a double-helix structure. The...