RNA-based therapeutics have been under development for over 30 years however, the COVID-19 pandemic has rapidly accelerated their development, chiefly with mRNA-based vaccines against the SARS-Cov2 virus by Moderna and BioNTech/Pfizer. A key part of the technology are the lipid nanoparticles (LNPs) used to deliver RNA. Naked RNA cannot simply be injected as it is immunogenic, easily susceptible to enzymatic degradation, and is not taken up by cells. To overcome these problems, RNA is packaged up in LNPs that protect it from degradation while circulating, allow it to enter cells, then release the contents into the cytoplasm so the RNA can be used by ribosomes for protein synthesis.
ALC-0315 is an ionizable lipid which has been used to form lipid nanoparticles for delivery of RNA. ALC-0315 is one of the components in the BNT162b2 vaccine against SARS-CoV-2 in addition to ALC-0159, DSPC, and cholesterol.
cKK-E12 has been used to deliver siRNA in mice, rats, and primates. It shows low toxicity and is selective for liver parenchymal cells over liver, heart, lung, and kidney endothelial cells.
SM-102 is an ionizable lipid used in lipid nanoparticles (LNPs) and can be found in some formulations of mRNA based vaccines.
The LNP Trailblazer Kits LNP Trailblazer Kits are designed for quick assembly and assessment of RNA-LNPs in biological systems. Each kit includes a buffer for preparation of RNA cargo and the necessary lipids to form lipid nanoparticles.
Ionizable lipids are lipid molecules that have neutral charge at physiological pH, but obtain a positive charge when there is a shift to low due to protonation. The pH-dependent charge of these lipids improves their capacity for cargo delivery to cells as their neutral charge decreases the number of interactions with the anionic membranes of most cells.
When trafficked to low-pH cellular compartments such as the endosome, they become protonated and shift to a positive charge. This is thought to destabilize the local organelle membrane and allow for escape of nanoparticles into the cytosol where their cargo can be delivered.
LNPs are typically composed of four types of lipids: ionizable lipid, PEGylated lipid, cholesterol, and neutral phospholipids. The PEGylated lipids account for 0.5-3% of the lipid content of the LNP and are incorporated to increase the circulatory half-life in the body. Cholesterol is a structural “helper” lipid that makes up a significant part of the LNP (40-50%) and improves efficacy possibly by promoting membrane fusion and promoting endosomal escape. Similarly, the synthetic phospholipids (~10%) are also commonly used as structural “helper” lipids in LNP formulation to promote cell binding.
LNPs have already displayed great therapeutic benefit as seen with the recent development of mRNA based vaccines. Given their success with delivering nucleic acid cargo such as RNA, many drug developers and pharmaceutical companies are hoping that they may provide a more efficient mechanism for delivering novel gene therapies. Read more on our blog ⇒
LNPs have already displayed great therapeutic benefit as seen with the recent development of mRNA based vaccines. Given their success with delivering nucleic acid cargo such as RNA, many drug developers and pharmaceutical companies are hoping that they may provide a more efficient mechanism for delivering novel gene therapies. Read more on our blog ⇓