From the day I started to study, my fascination about how the human body works in health and disease was born. Early drug development is what drives me in my professional life. The main focus throughout my career, so far, has been directed towards finding a therapeutic drug for Duchenne muscular dystrophy (DMD). During my Ph.D., I have worked on improving the delivery of exon skipping antisense oligonucleotides for treating DMD using tissue-homing peptides. Currently, I am investigating a hit-and-run delivery system seeking to introduce CRISPR-Cas9 complexes into muscle progenitor cells and, in doing so, repair defective DMD alleles. I will do this by investigating the feasibility and utility of hijacking the cellular entry processes finely orchestrated by adenoviral capsids to deliver, in a temporally controlled manner, strict amounts of Cas9 proteins and/or gRNAs into target cells.
I started my career in 2006 at the VUMC, Amsterdam, as a research technician and, as such, I have subsequently joined the LUMC in 2008. I started my Ph.D. in 2012 in the DMD Genetic Therapy Group of Prof. Annemieke Aartsma-Rus, at the Department of Human Genetics at the LUMC. I obtained my Ph.D. degree in July 2017. My Ph.D. focused on improving the delivery of 2’-O-methylphosphorothioate antisense oligonucleotides (AONs) to skeletal and cardiac muscles for treating Duchenne muscular dystrophy. I used my knowledge on phage display technology and next generation sequencing to identify tissue-specific homing peptides to improve AON delivery. I continued my career as a bioanalytical scientist/project leader at the Centrum for Human Drug Research, in Leiden. There I studied the mechanism of action of an anti-microbial peptide compound. In November 2018, I joined the Department of Cell and Chemical Biology at the LUMC as a Postdoctoral fellow.
Cyclic Peptides to Improve Delivery and Exon Skipping of Antisense Oligonucleotides in a Mouse Model for Duchenne Muscular Dystrophy.
Jirka SMG, 't Hoen PAC, Diaz Parillas V, Tanganyika-de Winter CL, Verheul RC, Aguilera B, de Visser PC, Aartsma-Rus AM.
Mol. Ther. 26, 132-147 (2018). doi: 10.1016/j.ymthe.2017.10.004.
Evaluation of 2’- deoxy-2’-fluoro antisense oligonucleotides for exon skipping in Duchenne muscular dystrophy
Jirka SMG, Tanganyika-de Winter CL, van der Meulen JW, van Putten M, Hiller M, Vermue R, de Visser PC and Aartsma-Rus AM.
Mol. Ther. Nucleic Acids 4, e265 (2015). doi: 10.1038/mtna.2015.39.
Peptide conjugation of 2'-O-methyl phosphorothioate antisense oligonucleotides enhances cardiac uptake and exon skipping in mdx mice.
Jirka SMG, Heemskerk H, Tanganyika-de Winter CL, Muilwijk, Pang KH, de Visser PC , Janson A, Karnaoukh TG, Vermue R, ‘t Hoen PAC, van Deutekom JCT, Aguilera B and Aartsma-Rus AM.
Nucleic Acid Ther. 24, 25-36 (2014). doi: 10.1089/nat.2013.0448.