Lipid Nanoparticles, a New Direction for Genetic Vector Development

January 7, 2022 | | 6 min read

Cationic Lipids – Cationic Lipids are positively charged lipids that help form the nanoparticle around the mRNA. This works because of the attractive forces between the cationic lipid and the negative charges in the phosphate backbone of mRNA8. The DOTMA depicted above is an example of a commonly used cationic lipid. Note the nitrogen with a positive charge due to the four alkyl groups coming off of it, making the lipid cationic.

PEGylated Lipids – Polyethylene Glycol (PEG), a polymer with repeating units of [CH2-CH2-O], can be anchored onto a lipid and incorporated into the lipid nanoparticle. The polyethylene forms a layer of long hairs on the outer surface of the nanoparticle, shielding it from the environment. This increases the nanoparticle lifetime in circulation but unfortunately also reduces the chances of the nanoparticle entering the cell.8 The DSPE-PEG2000 depicted above is an example of a commonly used PEGylated Lipid. Note the region in brackets with the number 45, which is the PEG component of the molecule with 45 repeating units of the [CH2-CH2-O] motif.

Overall, lipid nanoparticles have almost no downsides in comparison to viral vectors. Much more research needs to be done to expand on and improve the functionalization of these lipid nanoparticles for more controllable and effective targeting to improve their adaptability as a genetic vector. While still a relatively new technology, lipid nanoparticles provide a promising new vector that delivers DNA or RNA that may overtake the applications of viral vectors.

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