The N/P ratio is crucial in transfection, especially with mRNA and lipid nanoparticles (LNPs). This ratio, representing nitrogen to phosphate, significantly impacts nanoparticle properties such as size and encapsulation efficiency.

What is the N/P Ratio?

The N/P ratio indicates the molar ratio between the amine groups (N) of the ionizable lipid and the phosphate groups (P) of the cargo. For RNA, there's one phosphate group per base, and for DNA, there are two phosphate groups per base. Typical N/P ratios range from three to six, varying with the cargo and ionizable lipid used. Notably, Pfizer and Moderna use a 6:1 N/P ratio in their mRNA vaccine formulations.

How to Calculate the N/P Ratio

Significance of the N/P Ratio

Optimizing the N/P ratio is vital as it influences LNP efficiency. A higher N/P ratio generally results in nanoparticles with more positive charges, enhancing interaction with negatively charged cell membranes, potentially increasing transfection efficiency and affecting cytotoxicity.

References:

1. Maier, M. A., et al. (2019). Biochemistry and pharmacology of mRNA. Mol Ther.
2. Payload distribution and capacity of mRNA lipid nanoparticles. ResearchGate.
3. The effect of lipid nanoparticles on mRNA delivery and biodistribution. ScienceDirect.
4. Recent advances in lipid nanoparticle formulations for mRNA delivery. PMC.