Prize: Gold Medal
Promising Novel Gene Therapy and Pharmacological Approaches for GSD 1a: Prime Editing, mRNA Delivery and Ataluren
One of the rare diseases throughout the world is Glycogen Storage Disease which appears due to problems in glycogen metabolism. Among various subtypes of GSD, GSD Type 1a is the most abundant one of GSD Type 1, seen in approximately 80%, caused by different kinds of mutations in glucose-6-phosphatase (G6PC) gene in human chromosome 17q21. G6PC gene encodes for glucose-6-phosphatase (G6Pase) protein, which cleaves glucose-6-phosphate into glucose and inorganic phosphate (Pi), and GSD Type 1a patients fail to breakdown glucose-6-phosphate due to several mutations in G6PC gene. In our study, we aim to create new therapeutic approaches for GSD 1a. We collected mutation data of 57 GSD Type 1a patients from Turkey from Intergen Genetic and Rare Disease Diagnosis Research and Application Center. According to the data, 16 types of mutations were observed in G6PC gene. Allele frequencies of these mutations are calculated as 59% for R83C/H, 11% for W160*, 7% for G270V and 28% for others which have less frequency. Up to now, tertiary protein structure of G6Pase has not been structured yet. To understand the possible impacts of these mutations, we statistically obtained possible tertiary structure predictions of G6Pase by running 5 different tools. At the end of the study, we suggest two effective and promising therapeutic methods for GSD 1a, Prime Editing for R83C/H mutations, and mRNA delivery, for other mutations, in addition to a promising, commercially available drug suggestion for patients with W160*, W86* and S15* mutations, although the drug belongs to another disease. These gene therapy systems will be delivered in hepatocyte-targeting lipid nanoparticles (LNP).
Cemre Uçaryılmaz has graduated from Molecular Biology and Genetics, Boğaziçi University in 2019.
Cemre Uçaryılmaz is a masters student at Koc University, Cellular and Molecular Medicine.
Sezgin Mengi has graduated from Molecular Biology and Genetics, Boğaziçi University in 2019.
Sezgin Mengi is a masters student at Sabancı University, Molecular Biology, Genetics and Bioengineering.
Aysun Mantaş has graduated from Nevsehir Hacı Bektas Veli University
Department of Molecular Biology and Genetics.
Fatma Nur Güler
Fatma Nur Güler has graduated from Nevşehir Hacı Bektaş Veli University Department of Molecular Biology and Genetics in 2020.
Büşra Şeniz Demir
Büşra Şeniz Demir has graduated from Nevşehir Hacı Bektaş Veli University Department of Molecular Biology and Genetics in 2020.
Büşra Şeniz Demir is a masters student at Erciyes University, Medical Biology.