Use of miRNA in gene therapy

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.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