The Project

Chimeric Antigen Receptor T (CAR T) cell therapy is a type of immunotherapy based in the ex-vivo engineering of patient T-lymphocytes to produce special chimerical receptors on their surface that target specifically tumoral cells when re-introduced in the patient. CAR T cell therapy targeting CD19 is showing very promising results with recurrent and refractory Chronic Lymphocytic Leukaemia. However: i) since today’s CAR T lymphocytes stay active indefinitely, patients experience permanent eradication of normal B-cells and require monthly infusions of immunoglobulins for survival, ii) T-cells are modified using lenti- or retroviral vectors, which, though acceptably safe, they are not free of oncogenic insertional mutagenesis risk and consequent regulatory barriers.

To overcome permanent elimination of B-cells, mRNA transfections are more and more used as a tool for transient protein overexpression. Besides, it is recommended the use of abiotic delivery vehicles that involves no risks of insertional mutagenesis. The use of mRNA as an overexpression tool is challenging since isolated mRNA is easily degraded, and protein levels quickly decline after 24-48h, while the treatment should last for at least 2-3 weeks in order to eradicate tumoral cells from the patient. Current methods for non-viral mRNA delivery, especially lipofectamine or electroporation, are quite toxic.

We propose to bind the mRNA to Au (solid and hollow) NPs functionalized with amine terminated groups (for protein sponge and endosomal escape) as a safer way to transport mRNA to the cytosol via endocytosis. We will control the slow release of the loaded mRNA inside the cell, therefore extending the mRNA half-life and protein expression. AuNPs are of special interest for delivery due to their biocompatibility, tuneable surface chemistry, and their special optical and electronic properties that allow fine monitoring of the evolution, distribution and modifications of them and their chemical environment.