Lipid nanoparticles (LNPs) are nanoscale delivery vehicles made primarily of lipids that self-assemble into stable particles. They are widely used for delivering nucleic acids like mRNA, siRNA, or DNA into cells, and have become especially prominent due to their role in mRNA vaccines (like the COVID-19 vaccines from Pfizer-BioNTech and Moderna). It is a valuable technique in transfection of cells where the mRNA that is delivered is used for protein translation.
What Are Lipid Nanoparticles?
LNPs are typically 50–150 nm in size and consist of a core-shell structure:
| Component | Function |
|---|---|
| Ionizable or cationic lipids | Bind to negatively charged nucleic acids; help with endosomal escape. |
| Phospholipids | Support membrane structure. |
| Cholesterol | Adds stability and fluidity. |
| PEG-lipids (polyethylene glycol) | Prevent aggregation, extend circulation time in vivo. |
How Do They Work?
-
Encapsulation of Nucleic Acid:
-
The LNPs are formed by rapidly mixing lipids (in ethanol) with nucleic acids (in aqueous buffer), causing self-assembly into nanoparticles that encapsulate the payload.
-
-
Cellular Uptake:
-
LNPs are taken up by cells via endocytosis.
-
-
Endosomal Escape:
-
Ionizable lipids become positively charged in acidic endosomes, destabilizing the membrane and enabling release of the nucleic acid into the cytoplasm.
-
-
Expression or Silencing:
-
mRNA is translated into protein.
-
siRNA or DNA performs its function depending on the design.
-
Applications of LNPs:
| Field | Use |
|---|---|
| Vaccines | mRNA delivery (e.g., SARS-CoV-2 spike protein). |
| Gene therapy | DNA, mRNA, or CRISPR-Cas9 delivery. |
| RNAi therapy | siRNA or miRNA delivery to silence genes. |
| Cancer therapy | Delivering therapeutic RNAs or drugs. |
Components Of Lipid Nanoparticles
Advantages:
-
Protects fragile RNA/DNA from degradation.
-
Non-viral — safer and less immunogenic than viral vectors.
-
Scalable and adaptable for different nucleic acids.
-
Can be targeted to specific tissues by modifying lipid composition.
Challenges and Considerations:
-
Immunogenicity – Some lipid formulations can trigger immune responses.
-
Tissue targeting – Most LNPs naturally target the liver, so modifications are needed for other organs.
-
Stability – PEG-lipids improve circulation but may reduce cellular uptake.
Real-World Example:
-
Pfizer-BioNTech & Moderna COVID-19 vaccines use LNPs to deliver mRNA encoding the SARS-CoV-2 spike protein.
-
Onpattro® (patisiran) – the first FDA-approved RNAi therapeutic, uses LNPs to deliver siRNA to treat hereditary transthyretin-mediated amyloidosis.
Leave a Reply