Related Experiment Video
Updated: Aug 6, 2026
08:29
Generation of Cationic Nanoliposomes for the Efficient Delivery of In Vitro Transcribed Messenger RNA
Published on: February 1, 2019
Ionizable Silyl Lipids with Distinct Membrane Fluidity and mRNA Delivery Profiles
Leah A Patterson1, Wendy N Tran1, Yuliia Humeniuk1
1Department of Chemistry, University of California, One Shields Avenue, Davis, California 95616, United States.
ACS Chemical Biology
|July 16, 2026
Summary
New silyl lipids offer tunable control over lipid nanoparticle properties. Single-chain variants enhance RNA encapsulation and mRNA transfection, demonstrating potential for optimized delivery systems.
Area of Science:
- Biochemistry
- Materials Science
- Nanotechnology
Background:
- Lipid nanoparticles (LNPs) are crucial for nucleic acid delivery.
- Ionizable lipids are key components controlling LNP stability and function.
- Modulating LNP properties like membrane fluidity is essential for optimizing delivery efficiency.
Purpose of the Study:
- To synthesize and evaluate novel ionizable silyl-lipids with single (MA) and double (DA) alkyl chains.
- To investigate the impact of silyl lipid structure on LNP properties, including RNA encapsulation efficiency (EE), mRNA transfection, particle size, and membrane fluidity.
- To explore the potential of these silyl lipids for rational modulation of LNP performance.
Main Methods:
- Synthesis of single-chain (MA) and double-chain (DA) ionizable silyl-lipids.
- Characterization of LNP properties: encapsulation efficiency (EE), particle size, and morphology (cryo-transmission electron microscopy - cryo-TEM).
- Assessment of membrane fluidity using C-Laurdan fluorescence assay.
- Evaluation of mRNA transfection efficiency in vitro.
Main Results:
- Silyl lipid tail substituents influenced LNP properties, membrane fluidity, and transfection efficiency.
- MA silyl lipids produced LNPs with more fluid membranes compared to DA lipids (similar to ALC-0315), which formed more rigid membranes.
- MA-based LNPs exhibited higher EE and distinct particle morphology.
- mRNA transfection efficiency varied with particle composition; MA lipids showed efficacy even without helper lipids.
- Phenyl-containing cationic silyl lipids significantly enhanced mRNA transfection compared to controls.
Conclusions:
- Single- and double-chain ionizable silyl lipids provide a means to rationally modulate LNP membrane fluidity and performance.
- MA silyl lipids offer advantages in RNA encapsulation and mRNA transfection, highlighting their potential for advanced delivery systems.
- The structural design of silyl lipids is critical for optimizing LNP characteristics and enhancing therapeutic efficacy.
More Related Videos
15:55Long-term Silencing of Intersectin-1s in Mouse Lungs by Repeated Delivery of a Specific siRNA via Cationic Liposomes. Evaluation of Knockdown Effects by Electron Microscopy
Published on: June 21, 2013
08:10Synthesizing Lipid Nanoparticles by Turbulent Flow in Confined Impinging Jet Mixers
Published on: August 23, 2024
Related Concept Videos
01:26Membrane Fluidity
Membrane fluidity is explained by the fluid mosaic model of the cell membrane, which describes the plasma membrane structure as a mosaic of components—including phospholipids, cholesterol, proteins, and carbohydrates—that gives the membrane a fluid character.
Mosaic nature of the membrane
The mosaic characteristic of the membrane helps the plasma membrane remain fluid. The integral proteins and lipids exist as separate but loosely-attached molecules in the membrane. The membrane is a relatively...
Mosaic nature of the membrane
The mosaic characteristic of the membrane helps the plasma membrane remain fluid. The integral proteins and lipids exist as separate but loosely-attached molecules in the membrane. The membrane is a relatively...
01:23Membrane Fluidity
Cell membranes are composed of phospholipids, proteins, and carbohydrates loosely attached to one another through chemical interactions. Molecules are generally able to move about in the plane of the membrane, giving the membrane its flexible nature called fluidity. Two other features of the membrane contribute to membrane fluidity: the chemical structure of the phospholipids and the presence of cholesterol in the membrane.Fatty acids tails of phospholipids can be either saturated or...
01:35Asymmetric Lipid Bilayer
Biological membranes show uneven distribution of different types of lipids in the inner and outer layers, resulting in transverse asymmetric membranes. The treatment of the erythrocyte membrane with the enzyme phospholipase confirmed the asymmetric nature of the lipid bilayer. The enzyme hydrolyzes lipids into fatty acids and hydrophilic groups. The phospholipase acts only on the outer layer of the membrane, while the inner layer remains intact. The phospholipase treatment resulted in 80%...
01:18Membrane Domains
The membrane domains concentrate specific lipids and proteins at one place within the membrane, which helps in cell signaling, adhesion, and other critical cellular processes. These domains can differ in size, composition, function, and lifespan.
Protein Domains
The membrane comprises a group of distinct proteins responsible for carrying out a cell's specific function. For example, the plasma membrane of the human sperm, or a single germ cell, contains a unique set of proteins in the anterior...
Protein Domains
The membrane comprises a group of distinct proteins responsible for carrying out a cell's specific function. For example, the plasma membrane of the human sperm, or a single germ cell, contains a unique set of proteins in the anterior...
02:30siRNA - Small Interfering RNAs
Small interfering RNAs, or siRNAs, are short regulatory RNA molecules that can silence genes post-transcriptionally, as well as the transcriptional level in some cases. siRNAs are important for protecting cells against viral infections and silencing transposable genetic elements.
In the cytoplasm, siRNA is processed from a double-stranded RNA, which comes from either endogenous DNA transcription or exogenous sources like a virus. This double-stranded RNA is then cleaved by the ATP-dependent...
In the cytoplasm, siRNA is processed from a double-stranded RNA, which comes from either endogenous DNA transcription or exogenous sources like a virus. This double-stranded RNA is then cleaved by the ATP-dependent...
01:19Fluid Mosaic Model
Scientists identified the plasma membrane in the 1890s and its principal chemical components (lipids and proteins) by 1915. The model for plasma membrane structure, proposed in 1935 by Hugh Davson and James Danielli, was the first model to be widely accepted in the scientific community. The model was based on the plasma membrane's "railroad track" appearance in early electron micrographs. Davson and Danielli theorized that the plasma membrane's structure resembled a sandwich with the analogy of...