Nanoscience: 3rd generation of nanoparticles is coming…

Well… It is no joke! The 3^rd generation of LNP (lipid nanoparticle) is on the way to be launched! The only problem is that nobody clearly understands this technology (see also here and here), even its 1^st or 2^nd generations. Let’s see for the explanation:

LNP technology for indications involved with the liver is the most mature delivery system within RNAi therapeutics. Current LNP (lipid nanoparticle) technology is in its 2nd generation (such as ALN-PCS, ALN-TTR02) which has ~100-fold increased potency and better safety than 1st generation (such as ALN-VSP, ALN-TTR1) offerings.

One of the issues with the current 2nd generation LNP is that they have long elimination half-lives in plasma and tissues. It is suspected that they might accumulate over time and lead to cytotoxicity in target cells with chronic dosing. Specifically, they end up building up in the liver and spleen.

The idea behind the new 3rd generation LNP technology being researched by Alnylam (ALNY) is to create a rapidly eliminating LNP formulation (reLNP). The idea behind reLNP is to have them be rapidly biodegradable so this accumulation cannot occur. Observe these preclinical results of how these rapidly eliminating LNP are eliminated in the plasma, liver and spleen. It looks like 2 reLNP lipids are being evaluated with different elimination half-lives. I assume that 2 reLNPs are being researched so further experimentation can find the sweet spot for therapeutic application.

Then we can see a lot of experimental pics in the rest of the article clearly convincing us in the advantages of the 3^rd generation of LNP. Basically I think it is worth to continue developing the new generations of LNP if the former ones were not efficient in the creation of new efficient drugs. I hope that 30^th or 50^th generation will be definitively successful – just not to give up!