ESR10: Optimisation, delivery and tolerability of antisense oligonucleotides to treat STGD1 patients with the most common splice mutations in ABCA4
|
Melita Kaltak
My name is Melita Kaltak and I will be joining the StarT crew the 1st of September as a PhD student within ProQR located in Leiden, the Netherlands. It will be the first time for ProQR to be involved in a Marie Curie Network, and I am super happy to be part of that! I am 24 years old, originally coming from Croatia, but I lived for many years in Italy and Sweden while studying. Recently I graduated in Functional Genomics at the University of Trieste in Italy, and, since then, I am working as a Laboratory Engineer within a research group at the Sahlgrenska Cancer Center in Gothenburg, Sweden. I have many hobbies, but I would say that I am most passionate about music. In my free time I play the drums, and I like to attend concerts and music festivals. Most of the time you can spot me among the first rows checking the drum player’s technique. Beside music, I love sports and spending time outdoors in the nature. Before discovering science, for many years I played tennis and was part of a volleyball club in the first Croatian league. I am very excited for having the opportunity to work with ProQR and being part of an important European project such as StarT, and I will be more than happy for contributing with my knowledge in all missions and challenges together with other 13 PhD students and their supervisors. |
Abstract
ProQR is currently in Phase IIa clinical development with a splice modulating AON (QR-110) targeting the deep-intronic c.2991+1655A>G mutation in LCA type 10. In addition, they have two additional AON programs in Usher syndrome targeted all exon-13 mutations (QR-421a) and c.7595-2144A>G (QR-411a), respectively, in pre-IND/CTA enabling studies. ProQR is also in the discovery phase with regards to an intronic ABCA4 mutation (c.5461-10T>C), one of the most frequent mutations underlying STGD1 that results in the exclusion of exon 39, or exon 39 and exon 40 together, from the mRNA, leading to a frameshift. ESR10 will continue this program and optimise the sequence and chemistry of the final molecule to generate a clinical development candidate. This lead candidate will be further optimised by determining the extent of target engagement using digital-droplet PCR, immune-profiling against human donor T-lymphocyte panels, delivery to photoreceptors tolerability and pharmacokinetic parameters following intravitreal injection of mouse and rabbit models.
ProQR is currently in Phase IIa clinical development with a splice modulating AON (QR-110) targeting the deep-intronic c.2991+1655A>G mutation in LCA type 10. In addition, they have two additional AON programs in Usher syndrome targeted all exon-13 mutations (QR-421a) and c.7595-2144A>G (QR-411a), respectively, in pre-IND/CTA enabling studies. ProQR is also in the discovery phase with regards to an intronic ABCA4 mutation (c.5461-10T>C), one of the most frequent mutations underlying STGD1 that results in the exclusion of exon 39, or exon 39 and exon 40 together, from the mRNA, leading to a frameshift. ESR10 will continue this program and optimise the sequence and chemistry of the final molecule to generate a clinical development candidate. This lead candidate will be further optimised by determining the extent of target engagement using digital-droplet PCR, immune-profiling against human donor T-lymphocyte panels, delivery to photoreceptors tolerability and pharmacokinetic parameters following intravitreal injection of mouse and rabbit models.
