Delivery of small nucleic acids by conjugation to carbohydrates and lipids as novel research and therapeutic tools

399 p. : il., graf.

Small nucleic acids present a great potential to silence specific genes or inhibit the biological activity of specific proteins. Unfortunately, their poor cellular accessibility presents a big challenge for developing an efficient delivery system. In this regard, conjugation of appropriate molecules to small nucleic improves their pharmacokinetic behaviours and cellular uptake efficiencies, endowing them with entirely new properties. In the present work different carbohydrate- and lipid-oligonucleotide conjugates have been studied as novel tools for targeted delivery and enhancement of cellular permeability. The results obtained in this work indicate that keeping a certain distance between DNA and sugar modification could be important for a better incorporation of this type of conjugates into the target cell. Also long or double-tailed lipid modifications are preferred for an enhanced incorporation of lipid-oligonucleotide conjugates into membrane-model and cell systems.