Oligo-Oleyl-Spermine Oligonucleotide Conjugate, Cationic-Amphiphiles, and Low-Molecular-Weight-Hydrogelators for Development of siRNA Delivery Systems
- Oligo-Oleyl-Spermine Oligonucleotide Conjugate, Cationic-Amphiphiles, and Low-Molecular-Weight-Hydrogelators for Development of siRNA Delivery Systems
- Patil, Sachin Prakash
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- Small interfering RNA (siRNA) represents the latest entry into the oligonucleotides therapeutics class. This technology is based on post- transcriptional gene silencing, more commonly referred to as RNAi, an endogenous, evolutionarily conserved, common pathway for regulation of gene expression. In the 1990s it was discovered that RNAi can be tapped artificially by addition of exogenous synthetic double-stranded small RNA sequences which, when exhibiting perfect complementarity to the mRNA sequence, lead to efficient mRNA cleavage (siRNA effect). Since this Nobel Prize-winning discovery, RNAi has become a widely used tool to probe gene function, routinely applied to cell culture systems and lower-organism models. However, siRNA itself cannot cross the cell membrane due to its inherent instability, large molecular weight and anionic nature. For this reason, a carrier that protects, delivers and unloads siRNA is required for successful gene silencing. The goal of this research was to develop potential siRNA delivery systems for their in vitro and in vivo applications based on cationic amphiphiles. Furthermore the delivery systems were constructed in three different ways (i) Oligo-oleyl-spermine oligonucleotide conjugate (ii) Cationic amphiphiles from nucleoside and phosphorylethanolamine (iii) Low molecular weight hydrogelators (LMWGs) from vitamins and nucleosides.
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