PhD defence M.J.R. Ruigrok

siRNA in precision-cut lung slices: knocking down fibrosis?

Idiopathic pulmonary fibrosis (IPF) is a disease with a poor prognosis that is marked by excessive scarring in the lungs, leading to breathlessness and, ultimately, death. To slow the progression of IPF, physicians often prescribe drugs, such as nintedanib or pirfenidone. Unfortunately, these drugs can cause severe side effects, have a limited therapeutic effect, and do not cure the disease. As a result, there remains an unmet medical need for safer and more effective drugs. Developing such drugs, however, is difficult as the initial cause of IPF is unknown. To investigate or to treat IPF, small interfering RNA (siRNA) could be used. siRNA is part of a new class of compounds that can be used to lower the expression of specific genes, thereby decreasing the synthesis of specific proteins. The objective of Mitchel Ruigrok his research was to evaluate whether siRNA could be used to treat lung fibrosis. To address the poor translation from cell cultures to patients, he first developed a method to deliver siRNA into precision-cut lung slices - an experimental model that recapitulates many features of the lungs. After further optimizing lung slice culturing conditions, this method was applied to determine whether expression of a gene involved in the production of scar tissue could be lowered to alleviate fibrosis. Taken together, results presented in this thesis support the use of siRNA to investigate fibrosis in precision-cut lung slices.

Promotores: Prof.dr. H.W. Frijlink and Prof.dr. P. Olinga