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Olen nõus
"Muu" projekt SARMP12219T
SARMP12219T "miRNA-põhise asendusteraapia meetodite arendamine (1.09.2012−31.08.2015)", Ana Rebane, Tartu Ülikool.
3.2.0701.12-0052
SARMP12219T
miRNA-põhise asendusteraapia meetodite arendamine
Development of miRNA replacement therapy methods
Development of miRNA replacement therapy methods
1.09.2012
31.08.2015
Teadus- ja arendusprojekt
Muu
ValdkondAlamvaldkondCERCS erialaFrascati Manual’i erialaProtsent
1. Bio- ja keskkonnateadused1.12. Bio- ja keskkonnateadustega seotud uuringud, näiteks biotehnoloogia, molekulaarbioloogia, rakubioloogia, biofüüsika, majandus- ja tehnoloogiauuringudT490 Biotehnoloogia 1.5. Bioteadused (bioloogia, botaanika, bakterioloogia, mikrobioloogia, zooloogia, entomoloogia, geneetika, biokeemia, biofüüsika jt100,0
AsutusRollPeriood
Tartu Ülikoolkoordinaator01.09.2012−31.08.2015
AsutusRiikTüüp
SA Archimedes
PerioodSumma
01.09.2012−31.08.2015252 972,65 EUR
252 972,65 EUR
Biotehnoloogia teadus- ja arendustegevuse toetamine

MicroRNAs (miRNAs) are recently discovered 21-23 nucleotides long single-stranded RNAs, which function together with partner proteins and mainly cause gene silencing by degradation of target mRNAs or inhibition of translation. Each particular miRNA has numerous targets and each target mRNA is frequently regulated by multiple miRNAs. The importance of miRNAs in human health is becoming increasingly clear, since aberrant regulation of miRNAs is functionally linked to many human disorders, including inflammatory diseases and cancer. Thus, modification of the expression of miRNAs via either over-expression or inhibition can potentially be used in therapeutic purposes. However, this is not yet widely used mainly because of complicated delivery issues. Major obstacles for in vivo clinical applications of oligonucleotides, including miRNAS, are the poor permeability of plasma membrane to nucleic acids and the sensitivity of oligonucleotides to enzymatic degradation. Hence, various delivery vehicles have been developed to ensure the transduction of oligonucleotides into cells. Among these, the cell-penetrating peptides have gained quickly broadening popularity as promising non-viral transmembrane delivery vectors. They have been used for delivery of siRNAs and miRNA inhibitors. The aim of the current project is to develop peptide-miRNA conjugation based method(s) to target stem cells, cancer initiator cells and primary cells. To develop peptide based vehicles for delivery of miRNAs into the cells and organisms, we propose a stepwise approach. We first test ability of peptide-miRNA conjugates to enter and function in various cell lines, primary cells and stem cells. Second, we will use 3D cultures and patient samples, and third, we test miRNA-peptide conjugates in in vivo mouse models. In addition, we plan to develop efficient and simple qPCR-based platform, which would enable to quickly analyze efficiency of miRNA functions in various study systems in collaboration with the partner company. We propose that current project leads to development of optimal complexing method(s) and delivery conditions for the peptide-miRNA conjugates depending on cell types as well as we will identify several miRNAs that have the strongest and desired impact on cellular phenotype and are most promising candidates for initiation of clinical trial in the future. The long-term vision of the current project is to develop miRNA replacement therapeutics.
MicroRNAs (miRNAs) are recently discovered 21-23 nucleotides long single-stranded RNAs, which function together with partner proteins and mainly cause gene silencing by degradation of target mRNAs or inhibition of translation. Each particular miRNA has numerous targets and each target mRNA is frequently regulated by multiple miRNAs. The importance of miRNAs in human health is becoming increasingly clear, since aberrant regulation of miRNAs is functionally linked to many human disorders, including inflammatory diseases and cancer. Thus, modification of the expression of miRNAs via either over-expression or inhibition can potentially be used in therapeutic purposes. However, this is not yet widely used mainly because of complicated delivery issues. Major obstacles for in vivo clinical applications of oligonucleotides, including miRNAS, are the poor permeability of plasma membrane to nucleic acids and the sensitivity of oligonucleotides to enzymatic degradation. Hence, various delivery vehicles have been developed to ensure the transduction of oligonucleotides into cells. Among these, the cell-penetrating peptides have gained quickly broadening popularity as promising non-viral transmembrane delivery vectors. They have been used for delivery of siRNAs and miRNA inhibitors. The aim of the current project is to develop peptide-miRNA conjugation based method(s) to target stem cells, cancer initiator cells and primary cells. To develop peptide based vehicles for delivery of miRNAs into the cells and organisms, we propose a stepwise approach. We first test ability of peptide-miRNA conjugates to enter and function in various cell lines, primary cells and stem cells. Second, we will use 3D cultures and patient samples, and third, we test miRNA-peptide conjugates in in vivo mouse models. In addition, we plan to develop efficient and simple qPCR-based platform, which would enable to quickly analyze efficiency of miRNA functions in various study systems in collaboration with the partner company. We propose that current project leads to development of optimal complexing method(s) and delivery conditions for the peptide-miRNA conjugates depending on cell types as well as we will identify several miRNAs that have the strongest and desired impact on cellular phenotype and are most promising candidates for initiation of clinical trial in the future. The long-term vision of the current project is to develop miRNA replacement therapeutics.
TegevusProtsent
Rakendusuuring100,0