Upotreba miRNA u genskoj terapiji

undergraduate thesis

• Title (english): Use of miRNA in gene therapy
• Author: Lara Jankaš
• Mentor: Petra Korać (mentor)
• Granter: University of Zagreb; Faculty of Science; (Department of Biology); Zagreb
• Defense date and country: 2022-09-19, Croatia
• Scientific / art field, discipline and subdiscipline: NATURAL SCIENCES; Biology

Abstract

miRNA su nekodirajuće molekule RNA duljine oko 22 nukleotida koje reguliraju
ekspresiju gena na posttranskripcijskoj razini vežući se na molekulu mRNA. Saznanje o
promjeni ekspresije određenih molekula miRNA u raznim bolestima dovelo je do ideje
njihove upotrebe u genskoj terapiji. U slučajevima kada je bolest uzrokovana smanjenom
ekspresijom miRNA potrebno je ponovno uspostaviti njenu funkciju. U ovu svrhu mogu se
koristiti oponašatelji miRNA, miRNA-agomiri, prekursori miRNA te plazmidi s genom za
miRNA. S druge strane miRNA-inhibitori su razvijeni s ciljem inhibicije prekomjerne
ekspresije miRNA. Većina inhibitora, poput antimiR-a i miRNA-spužvi, dizajnirana je s
ciljem vezanja na prekomjerno eksprimiranu miRNA. miRNA-maskiranje je strategija kojom
se umjesto direktne inhibicije dizajnira miRNA-maska koja se veže na molekulu mRNA i
sprečava vezanje ciljane miRNA na nju. Nekolicina terapeutika temeljenih na funkciji
molekula miRNA trenutno prolazi kroz klinička istraživanja. No, iako je postignut veliki
napredak u području upotrebe miRNA u genskoj terapiji ova se tehnologija još suočava s
brojnim izazovima, poput dopreme terapeutika na ciljano mjesto, poboljšanja stabilnosti
terapeutika i njegove otpornosti na nukleaze te smanjenja toksičnog utjecaja na organizam.

Abstract (english)

miRNAs are approximately 22 nucleotides long non-coding RNA molecules that
regulate gene expression at the posttranscriptional level by binding to the mRNA molecule.
The knowledge about the change in the expression of specific miRNA molecules in several
diseases led to the idea of their use in gene therapy. In cases where the disease is caused by
reduced miRNA expression, it is necessary to restore its function. miRNA mimics, miRNA
agomirs, miRNA precursors and miRNA-expressing plasmids can be used for this purpose.
On the other hand, miRNA inhibitors have been developed with the aim of inhibiting the
overexpression of miRNA molecules. Most inhibitors, such as antimiRs and miRNA-sponges,
are designed to bind to overexpressed miRNA. miRNA-masking is a strategy by which,
instead of direct inhibition, a miRNA-mask binds to the mRNA molecule and prevents the
target miRNA from binding to it. Several therapeutics based on knowledge about miRNA
function are currently undergoing clinical trials. But, although great progress has been made
in the field of miRNA use in gene therapy, this technology still faces numerous challenges.
Some of the most important challenges include delivering therapeutics to the target site,
improving the stability of therapeutics and its resistance to nucleases and reducing the toxic
impact on the organism.

• Keywords: mikroRNA; terapeutici; oponašanje; inhibicija
• Keywords (english): microRNA; therapeutics; mimic; inhibition
• Language: croatian
• URN:NBN: urn:nbn:hr:217:941167
• Study programme: Title: Molecular Biology; Study programme type: university; Study level: undergraduate; Academic / professional title: sveučilišni/a prvostupnik/prvostupnica (baccalaureus/baccalaurea) molekularne biologije (sveučilišni/a prvostupnik/prvostupnica (baccalaureus/baccalaurea) molekularne biologije)
• Type of resource: Text
• File origin: Born digital
• Access conditions: Open access
• Created on: 2022-10-06 12:49:27