Solid-phase supported design of carriers for therapeutic nucleic acid delivery.

Ana Krhac Levacic,Stephan Morys,Ernst Wagner

doi:10.1042/bsr20160617

Abstract

Nucleic acid molecules are important therapeutic agents in the field of antisense oligonucleotide, RNA interference, and gene therapies. Since nucleic acids are not able to cross cell membranes and enter efficiently into cells on their own, the development of efficient, safe, and precise delivery systems is the crucial challenge for development of nucleic acid therapeutics. For the delivery of nucleic acids to their intracellular site of action, either the cytosol or the nucleus, several extracellular and intracellular barriers have to be overcome. Multifunctional carriers may handle the different special requirements of each barrier. The complexity of such macromolecules however poses a new hurdle in medical translation, which is the chemical production in reproducible and well-defined form. Solid-phase assisted synthesis (SPS) presents a solution for this challenge. The current review provides an overview on the design and SPS of precise sequence-defined synthetic carriers for nucleic acid cargos.

Highlights

Administration of nucleic acids with therapeutic potential offers a promising approach for the treatment of several human diseases that reached already for medical use [1,2,3,4,5]
We focus on the design of nucleic acid delivery carriers that were synthesized by Solid-phase assisted synthesis (SPS)
Significant progress has been made in the field of nucleic acid delivery vehicles

Summary

Introduction

Administration of nucleic acids with therapeutic potential offers a promising approach for the treatment of several human diseases that reached already for medical use [1,2,3,4,5]. A series of researchers have applied the well-established method of SPS (see Figure 1) for developing linear [45,46,47,48,49,50,51,52,53,54,55] and branched [56,57,58,59,60,61,62] peptide-based, lipid-based [63,64,65,66], or artificial oligomer-based [66,67,68,69,70,71,72,73,74,75,76,77,78] sequence-defined nucleic acid carriers.

Results

Conclusion