Lipid nanoparticles (LNPs) enhance RNA stability primarily by providing a protective environment that shields the fragile RNA molecules from degradation. RNA is inherently unstable and easily degraded by enzymes like ribonucleases (RNases), which are abundant in biological systems. Here's how LNPs contribute to RNA stability:
1. Protection from RNases:
LNPs encapsulate RNA molecules, preventing exposure to RNases that would otherwise rapidly degrade the RNA. The lipid bilayer acts as a physical barrier, keeping the RNA safe from enzymatic degradation.
2. Preventing Hydrolysis:
RNA is also vulnerable to hydrolysis (breaking apart in water), particularly at physiological pH levels. The encapsulation within the hydrophobic core of the lipid nanoparticle reduces direct interaction between RNA and aqueous environments, thereby slowing down hydrolysis.
3. Reducing Immunogenicity:
Without protection, RNA can trigger immune responses, leading to its clearance and degradation. LNPs help mask the RNA from the immune system, reducing the likelihood of immune detection and degradation.
4. Facilitating Cellular Uptake:
LNPs enhance the delivery of RNA into cells by promoting cellular uptake through endocytosis. Once inside the cell, the LNPs help release the RNA into the cytoplasm, where it can perform its function, such as translating into a protein. This controlled release prevents premature degradation during transit.
5. Stabilizing mRNA Structure:
LNPs can also help stabilize the secondary structure of RNA. The lipid environment can prevent RNA from adopting unstable or reactive conformations that would otherwise contribute to its breakdown.
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