High-throughput approach for improving RNA nanoparticles as drug delivery agents

The ability of RNA to assemble into nanoparticles of different sizes and shapes has been exploited by academic and industrial research groups for drug delivery. In this project, the expertise of the candidate will be **combined** with **Sixfold Bioscience PODS and the robotic platforms in ROAR to develop a customised self-assembled RNA nanoparticle for cancer treatment.** Different RNA strands will be designed with personalised nucleotides attached. The research will focus on the **modification with clickable group**s compatible with the RNA synthesis. These will not interfere in the natural folding of the RNA structure, so its bioactivity will be preserved. In all cases, a HT approach will be followed. The moieties will be attached following sequential procedure after the PODS assembly; like how one would assemble LEGO(r) pieces.

The project will focus on **three aspects**:

**Study the cell internalization of the therapeutic agents**. Often PODS get trapped in liposomes after cell internalization. Multiple endosomal escape compounds will be tested for their release in the inner cells.

**Click-chemistry functionalization**: Different click chemistry reactions and conditions will be tested. The development will be done using HT. This methodology allows testing multiple variables in parallel using a minimum amount of reagents.

**PODS multi-functionalization**: Once the reaction conditions are optimized, multiple therapeutic functionalities will be introduced into the PODS structure.

Using ROAR facilities and Sixfold know-how, the candidate will be able to perform high-quality research that will lead to a breakthrough in the field of genetic therapies. The results obtained will not only open the door to a new therapeutic approach, but it will also give insight into how these systems operate in vivo.