"Mobilitas järeldoktori uurimistoetus" projekt MJD242
MJD242 (MJD242) "Targeted exosomes for the delivery of splice-switching oligonucleotides (SSOs) to muscle and brain (1.12.2011−30.11.2014)", Imre Mäger, Tartu Ülikool, Loodus- ja tehnoloogiateaduskond, Tartu Ülikooli Tehnoloogiainstituut.
MJD242
Targeted exosomes for the delivery of splice-switching oligonucleotides (SSOs) to muscle and brain
1.12.2011
30.11.2014
Teadus- ja arendusprojekt
Mobilitas järeldoktori uurimistoetus
ETIS klassifikaatorAlamvaldkondCERCS klassifikaatorFrascati Manual’i klassifikaatorProtsent
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 jt50,0
1. Bio- ja keskkonnateadused1.1. BiokeemiaP310 Proteiinid, ensümoloogia1.5. Bioteadused (bioloogia, botaanika, bakterioloogia, mikrobioloogia, zooloogia, entomoloogia, geneetika, biokeemia, biofüüsika jt50,0
PerioodSumma
01.12.2014−30.11.2014100 580,00 EUR
100 580,00 EUR

There are many neuromuscular disorders that have been associated, at least partly, with defects in pre-mRNA splicing, e.g. Duchenne muscular dystrophy (DMD), spinal muscular atrophy (SMA) and myotonic dystrophies, which remain untreatable with the current methods. There have been successful attempts to modulate splicing patterns by using splice switching antisense oligonucleotides (SSOs), some of them have even reached clinical trials, but they still have limitations. Firstly, high doses are required to achieve biologically relevant effects, and secondly, their uniform delivery to each target tissue and, furthermore, systemic delivery has remained an obstacle. Moreover, efficient strategies are lacking for their delivery over the blood-brain barrier (BBB). I aim to test several strategies to tackle the aforementioned limitations. Mainly I will concentrate on the use of exosomes as delivery vehicles of SSOs and develop targeted exosome strategies (e.g. the expression of targeting peptide ligands, including muscle and BBB targeting sequences, as fusions to exosome-bound proteins or by exogenously coating unmodified exosomes with peptides or nucleic acid aptamers). I will study different tools for loading exosomes with SSOs and different SSO chemistries will be tested. Also the possibilities for loading the exosomes with minicircles and circular ssDNA, which would be able to express SSOs upon reaching intracellular environment, will be investigated.