Targeted Delivery

In recent years, tremendous progress has been made in the field of RNA-based therapeutics, and the first therapeutics have already been tested in clinical trials. Despite a large number of promising preclinical and clinical studies, the effective and safe delivery of these RNA-based therapeutics in clinical trials has not yet been fully realized. Challenges to realization in clinical settings include off-target effects, inefficient uptake due to their surface charge and size, degradation by nucleases, or adverse immune responses. Therefore, in order to efficiently and specifically target the desired organ or cell type, packaging systems are essential. Of particular interest in our research group are magnetic nanoparticles such as SPIONs (Superparamagnetic Iron Oxide based Nanoparticles) for RNA or compound delivery, which due to their inherent magnetic moments can be controlled, heated, and tracked within the body using external magnetic fields. Magnetic fields penetrate the tissue without attenuation and allow non-contact manipulation and quantitative imaging deep inside the body.

Lipid nanoparticles (LNPs) can be directed to specific organs or cell types using one of two general strategies:

  1. Active Targeting: This approach involves attaching specific targeting ligands to lipids on the LNP surface, either before or after formulation. These ligands, such as antibodies, antibody fragments, peptides, sugars, or small molecules, bind to specific receptors expressed on target cells, facilitating receptor-mediated endocytosis of LNPs.
  2. Passive Targeting: This method leverages lipid composition by varying lipid subtypes and their molar ratios. This results in biophysically distinct particles with altered tissue tropism, enabling preferential accumulation in specific organs or cell types.

At IMTTS, in collaboration with Fraunhofer ITEM, we are actively developing LNP formulations for targeted RNA delivery using both active and passive targeting strategies. Additionally, by employing DNA barcoding techniques, we can evaluate multiple LNP formulations in parallel, significantly enhancing throughput while reducing the number of laboratory animals required, in line with the 3R principles (Replace, Reduce, Refine).

Key references:

Juchem M, Cushman S, Lu D, Chatterjee S, Bär C, Thum T. (2024) Encapsulating In Vitro Transcribed circRNA into Lipid Nanoparticles Via Microfluidic Mixing. Methods Mol Biol. 2765:247-260. https://doi.org/0.1007/978-1-0716-3678-7_14

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