Register for the upcoming PNI Teatime Webinar

 

Please fill out this form to register for the upcoming PNI Teatime Webinar Series: Beyond APOE and the LDLR: Identification of proteins regulated by ionizable lipid nanoparticles for RNA in liver and serum, presented by PD Dr. Matthias Bartneck from RWTH Aachen University.

 

Date: Wednesday, May 4

Time: 2:30pm GMT | 3:30pm CET

 

 

Webinar Abstract:

RNA therapeutics have emerged as important tools in vaccinations of billions of people. Prior to the mRNA-based vaccines, the first siRNA-based drug was approved in 2018. These RNA-based drugs are formulated as ionizable lipid nanoparticles (RNA-iLNP). Ionizable lipid nanoparticles (iLNP) represent the backbone of approved RNA therapeutics, enabling in vivo delivery for instance of messenger RNA (mRNA) and small interfering RNA (siRNA). The RNA-iLNP use a naturally existing transport system consisting of lipoprotein receptors and apoplipoprotein ligands to find their way into cells. The most commonly explored route for iLNP transport in the body is based on Apolipoprotein E (APOE) that binds to the iLNP and directs the RNA-iLNP to the LDLR expressed by liver cells (hepatocytes and other cell types).

 

Recently, we have discovered that specific immune cells express the LDLR in a dynamic fashion, a process that is regulated by APOE and RNA-iLNP. We thus studied the biodistribution of RNA-iLNP using non-invasive 3D whole body imaging. While it is known that Ldlr-/- mice exhibit a reduced uptake of RNA-iLNP, we observed that a specific inhibitor in Ldlr-/- mice leads to a restoration of RNA-iLNP uptake into the liver. A lack of Apolipoprotein receptor function also increases the uptake of RNA-iLNP by myeloid immune cells. Proteomics studies indicate that various proteins that are known to function i.e. in RNA binding and biological transport processes are regulated by RNA-iLNP. Furthermore, our analyses of the serum proteome indicates that there are pronounced and significant reductions of specific serum proteins that are known to potentially bind to the RNA-iLNP. Our data indicate that the transport of RNA-iLNP in the body involves many other proteins apart from APOE.