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

  1. Ugarte Uribe, Begoña
Supervised by:
  1. Itziar Alcorta Calvo Director

Defence university: Universidad del País Vasco - Euskal Herriko Unibertsitatea

Fecha de defensa: 28 May 2012

Committee:
  1. Alicia Alonso Izquierdo Chair
  2. César Augusto Martín Plágaro Secretary
  3. Ramón Eritja Casadellà Committee member
  4. Soledad Penadés Ullate Committee member
  5. Juan Carlos Morales Sánchez Committee member
Department:
  1. Bioquímica y Biología Molecular

Type: Thesis

Teseo: 115730 DIALNET lock_openADDI editor

Abstract

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 into membrane-model and cell systems.