Unik design av nanopartiklar innehållande guanidinium för att möjliggöra transport och frisättning av RNA-molekyler som cancerbehandlingar

Tidsperiod: 2017-01-01 till 2019-12-31

Projektledare: Johan Karlsson

Finansiär: Vetenskapsrådet

Bidragstyp: Bidrag för anställning eller stipendier

Budget: 3 150 000 SEK

A clinical strategy that has immense potential as treatment for many major human diseases is to control intracellular protein synthesis by using small interfering RNA (siRNA) or messenger RNA (mRNA) as therapeutic agents. However, yet as polar poly-anions they do not cross the non-polar membrane of cells. Clinical applications of RNA therapeutics have been hampered by the lack of delivery technologies that can facilitate effective delivery into cells. The proposed project will be carried out in the Wender group at Stanford University and they have from insights of how nature provide transport across cellular membranes developed Guanidinium-rich molecular transporters (GR-MoTrs). Not only does the guanidinium content enable cell-penetration, it is also positively charged and thereby able to complex RNA (negatively charged), and upon cell entry it becomes non-charged and thus releases the cargo. I will design GR-MoTrs to complex, deliver, and intracellularly release siRNA and mRNA in tumor cells. The objective with this novel delivery system is to achieve RNA therapeutic treatments for cancer. I will use siRNA molecules to suppress genes associated with the disease and I will use mRNA as a new approach of cancer immunotherapy. This project will involve material synthesis, material characterization, cell culture experiments, and pre-clinical studies, to create a MoTr that would serve as the next generation drug delivery system for RNA-therapeutic treatments of cancer.