Towards Targeted Delivery Systems: Ligand Conjugation Strategies for mRNA Nanoparticle Tumor Vaccines.

Kyle K L Phua

doi:10.1155/2015/680620

Abstract

The use of nanoparticles encapsulating messenger RNA (mRNA) as a vaccine has recently attracted much attention because of encouraging results achieved in many nonviral genetic antitumor vaccination studies. Notably, in all of these studies, mRNA nanoparticles are passively targeted to dendritic cells (DCs) through careful selection of vaccination sites. Hence, DC-targeted mRNA nanoparticle vaccines may be an imminent next step forward. In this brief report, we will discuss established conjugation strategies that have been successfully applied to both polymeric and liposomal gene delivery systems. We will also briefly describe promising DC surface receptors amenable for targeting mRNA nanoparticles. Practicable conjugation strategies and receptors reviewed in this paper will provide a convenient reference to facilitate future development of targeted mRNA nanoparticle vaccine.

Highlights

Messenger RNA has achieved great success in an increasing number of biological applications
The notion of nonviral genetic vaccination is increasingly associated with Messenger RNA (mRNA) instead of DNA
dendritic cells (DCs)-targeted nanoparticle gene delivery systems may be an imminent step forward for nonviral tumor vaccine delivery. In this brief report, established conjugation strategies for both polymeric and liposomal gene delivery systems will be described. This will be followed by a brief discussion on three promising DC receptors that are suitable for targeted delivery of mRNA nanoparticles for tumor vaccination

Summary

Introduction

Messenger RNA (mRNA) has achieved great success in an increasing number of biological applications. They include the optimization of the mRNA molecular structure [6, 7], direct in vivo administration of mRNA [8, 9], delivery routes [3, 4], evaluation of rationally designed gene carriers [10,11,12,13,14], and, recently, self-replicating RNA [15] Along this developmental trajectory, DC-targeted nanoparticle gene delivery systems may be an imminent step forward for nonviral tumor vaccine delivery. This will be followed by a brief discussion on three promising DC receptors that are suitable for targeted delivery of mRNA nanoparticles for tumor vaccination

Ligand Conjugation Strategies for Gene Delivery Systems

Targeting mRNA Nanoparticles via Selective Endocytic Pathways

Conclusion