Advanced Therapeutic Platforms based on Non-Classical Tripodal Interfering RNA Structural Format

S Sajeesh ,Dong-Ki Lee

doi:10.14800/rd.708

Abstract

The flexibility of human RNAi (RNA interference) machinery to accommodate unconventional structures has opened the way for the development of novel RNAi triggering formats, suitable for advanced therapeutic applications. Non-classical siRNA structural variants show improved functional features over the conventional siRNA formats including increased potency, reduced non-specific responses, and enhanced cellular delivery. These non-classical RNAi structures with enhanced structural and functional properties, in combination with appropriate delivery vehicles, can be an effective therapeutic module. Here we summarize our recent efforts on expanding the structural repertoire of classical siRNAs, using tripodal interfering RNA formats, to develop novel RNAi based therapeutics for advanced health-care applications.

Highlights

Ever since the significance of RNAi technology was established on a clinical setting, wide range of gene delivery systems have been evaluated for their systemic delivery [3].An ideal delivery technology, which can effectively regulate the therapeutic response of small interfering RNAs (siRNAs), seems a key factor in developing clinically relevant therapeutic RNAi platforms
Chemical conjugation and/or complementary hybridization strategies have been employed to generate polymeric siRNAs resembling the feature of long plasmid DNA, and this allowed the formation of stable polyelectrolyte complexes upon interaction with the cationic carriers [5,6,7]
Combination of three single stranded RNA (ssRNA) resulted in the formation of Y-shaped double stranded RNA (dsRNA) structures, with three different siRNA sequences embedded at each arm (Figure 1)

Summary

Introduction

Ever since the significance of RNAi technology was established on a clinical setting, wide range of gene delivery systems have been evaluated for their systemic delivery [3].An ideal delivery technology, which can effectively regulate the therapeutic response of siRNAs, seems a key factor in developing clinically relevant therapeutic RNAi platforms. Non-classical siRNA structural variants show improved functional features over the conventional siRNA formats including increased potency, reduced non-specific responses, and enhanced cellular delivery. These non-classical RNAi structures with enhanced structural and functional properties, in combination with appropriate delivery vehicles, can be an effective therapeutic module.

Results

Conclusion