diplomsko delo
Mateja Žvipelj (Author), Uroš Petrovič (Mentor), Uroš Petrovič (Thesis defence commission member), Mojca Žerjav-Tanšek (Thesis defence commission member), Polona Jamnik (Thesis defence commission member), Mojca Narat (Thesis defence commission member), Mojca Žerjav-Tanšek (Co-mentor)

Abstract

Glikogenoza tipa Ib je redka dedna bolezen z izstopajočimi metabolnimi in imunološkimi zapleti. Zaradi okvare prenašalnega proteina G6pt je onemogočena zadnja reakcija presnove glikogena v glukozo: pretvorba glukoze-6-fosfat v glukozo. Poglavitna posledica je življenjska ogroženost, saj se organizem med obroki ne more oskrbovati iz zalog glikogena in tako vzdrževati homeostaze krvnega sladkorja. Ker je G6pt v vseh celicah izražen protein, niso prizadeta le jetra kot glavno metabolno skladišče glikogena, temveč tudi funkcionalnost nevtrofilcev, ki vodi v nevtropenijo. Zapleti pa se pojavljajo še na številnih drugih nivojih. Zdravila za GSD Ib še ni, idealno pa bi popravilo okvaro gena za protein G6pt in želeno spremembo vneslo v vse celice telesa. Zanimivo osnovo za tovrstno rešitev predstavlja sistem CRISPR-Cas9, za glavnino mutacij dotičnega gena predvsem mehanizma prime editing (angl.) in base editing (angl.). Kljub vse pogostejši uporabi sistema CRISPR-Cas9 je ta po večini še vedno omejena na bazične raziskave. Tehnologija namreč še ni na stopnji, ki bi bila primerna (dovolj varna, učinkovita) za gensko terapijo. Poleg tega trenutno ne obstaja dovolj zadovoljiv (velikostno zmogljiv, varen) dostavni mehanizem, ki bi konstrukt z enako učinkovitostjo vnesel v najbolj prizadete organe oziroma tkiva, kaj šele v vse celice telesa. Vir napredka pa so vsekakor nadaljnje raziskave.

Keywords

glikogenoza tipa Ib;sistem CRISPR-Cas9;genska terapija;

Data

Language: Slovenian
Year of publishing:
Typology: 2.11 - Undergraduate Thesis
Organization: UL BF - Biotechnical Faculty
Publisher: [M. Žvipelj]
UDC: 606:616-056.7:602.6:599.892.3:602.64(043.2)
COBISS: 27677443 Link will open in a new window
Views: 612
Downloads: 112
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Other data

Secondary language: English
Secondary title: ǂThe ǂuse of CRISPR-CaS9 gene therapy for a treatment of glycogenosis in humans.
Secondary abstract: Gliyogenosis type Ib is a rare genetic disorder, mainly comprising metabolic and immunological issues. Due to deficiency of the G6PT transporter, the very last reaction of glycogen degradation to glucose, i.e. the conversion of glucose-6-phosphate to glucose is blocked. The principal consequence is life-threatening hypoglycemia as inability of utilizing glycogen storages between meals prevents the organism to maintain blood glucose homeostasis. Since G6PT is expressed ubiquitously, not only the liver, as the main glycogen reservoir, are affected, but also there are additional consequences, such as neutropenia. Currently there is no treatment for GSD Ib, however an ideal one would be able to correct the pathogenic mutation of the affected gene and insert the desired change in every single cell of the patient’s organism. CRISPR-Cas9 system would be an interesting technology towards this solution, especially prime editing and base editing mechanisms. However, current applications of CRISPR-Cas9 are mainly limited to basic research, as technology has not yet achieved an appropriate safety and efficacy level for gene therapy. Moreover, existing delivery mechanisms are confronted with similar safety and size capacity issues and are currently unable to reach all cells with the same efficacy. Regardless of all the challenges, new investigations are still the source of progress.
Secondary keywords: glycogenosis type Ib;CRISPR-Cas9 system;gene therapy;
Type (COBISS): Bachelor thesis/paper
Study programme: 0
Thesis comment: Univ. v Ljubljani, Biotehniška fak., Študij biotehnologije
Pages: VIII, 22 str., [5] str. pril.
ID: 12021440