Lipid Nanoparticles - How do they work - Structure of LNPs - LNPs in mRNA vaccine Pfizer/Moderna

Summary

In this informative lecture, Dr. Hazard explains the critical role of lipid nanoparticles (LNPs) in delivering mRNA for vaccines, particularly against COVID-19. He outlines how LNPs protect mRNA from degradation by enzymes, enabling it to enter cells where it can instruct the immune system to recognize the virus. The mechanism involves cationic lipids that bind to mRNA, forming a transport vehicle that facilitates cell entry through endocytosis. Once inside, the mRNA is released, allowing for the production of the viral spike protein, thereby training the immune response. This understanding highlights the innovative technology behind effective mRNA vaccines.

Takeaways

• 😀 Lipid nanoparticles (LNPs) are essential for delivering mRNA into cells effectively.
• 😀 Naked mRNA struggles to penetrate cell membranes due to its negative charge.
• 😀 LNPs protect mRNA from degradation by RNases present in extracellular fluid.
• 😀 The structure of LNPs includes ionizable cationic lipids that temporarily acquire a positive charge in acidic environments.
• 😀 At physiological pH, ionizable cationic lipids lose their charge, minimizing toxicity.
• 😀 PEGylated lipids in LNPs help prevent premature clearance by the immune system.
• 😀 LNPs can be designed to be either non-specific or specific to particular cell types.
• 😀 The process of endocytosis allows LNPs to enter cells by forming an endosomal sac.
• 😀 Inside the endosome, protons are pumped in, increasing the positive charge of cationic lipids.
• 😀 The release of mRNA occurs when cationic lipids fuse with the endosomal membrane, allowing mRNA to enter the cytoplasm.

Q & A

What are lipid nanoparticles?

Lipid nanoparticles are tiny, fat-like substances used to transport mRNA into cells, protecting it from degradation and facilitating its entry into the cell.

Why is mRNA not able to enter cells on its own?

Naked mRNA cannot efficiently cross cell membranes due to its negative charge and the presence of RNA-digesting enzymes in the extracellular fluid.

How do lipid nanoparticles protect mRNA?

Lipid nanoparticles protect mRNA from RNA-digesting enzymes and aid in its transport into cells by encapsulating it.

What role do cationic lipids play in lipid nanoparticles?

Cationic lipids are positively charged components that bind to negatively charged mRNA, allowing for encapsulation and protection during transport.

Why are ionizable cationic lipids preferred over permanently charged cationic lipids?

Ionizable cationic lipids are preferred because they are non-toxic at physiological pH, while permanently charged cationic lipids can disrupt cell membranes.

What is the function of polyethylene glycol (PEG) in lipid nanoparticles?

PEG helps to prevent the fusion and clumping of lipid nanoparticles and decreases their early clearance by immune cells, allowing for prolonged action in the body.

How do lipid nanoparticles enter cells?

Lipid nanoparticles enter cells through a process called endocytosis, where the cell membrane invaginates to engulf the nanoparticles as if they were nutrients.

What happens to lipid nanoparticles after they enter the cell?

Inside the cell, the lipid nanoparticles interact with the endosomal membrane, causing their structure to disrupt and release the encapsulated mRNA into the cytoplasm.

What triggers the release of mRNA from lipid nanoparticles?

The pumping of protons into the endosome increases the positive charge of the ionizable cationic lipids, leading to their fusion with the endosomal membrane and the release of mRNA.

What implications do lipid nanoparticles have for vaccine development?

Lipid nanoparticles enhance the delivery of mRNA in vaccines, improving the efficacy of immune responses against pathogens like the coronavirus.