Induction of Cytokines by Nucleic Acid Nanoparticles (NANPs) Depends on the Type of Delivery Carrier.

Yelixza I Avila,Jie Xu,Edward Cedrone,Kirill A Afonin,Morgan Chandler,Marina A Dobrovolskaia,Hannah S Newton,Neill J Liptrott,Melina Richardson,Jeffrey D Clogston

doi:10.3390/molecules26030652

Abstract

Recent insights into the immunostimulatory properties of nucleic acid nanoparticles (NANPs) have demonstrated that variations in the shape, size, and composition lead to distinct patterns in their immunostimulatory properties. While most of these studies have used a single lipid-based carrier to allow for NANPs’ intracellular delivery, it is now apparent that the platform for delivery, which has historically been a hurdle for therapeutic nucleic acids, is an additional means to tailoring NANP immunorecognition. Here, the use of dendrimers for the delivery of NANPs is compared to the lipid-based platform and the differences in resulting cytokine induction are presented.

Highlights

Laboratory for Cancer Research Sponsored by the National Cancer Institute, Frederick, MD 21702, USA; Department of Pharmacology and Therapeutics, Institute of Systems, Molecular and Integrative Biology, Abstract: Recent insights into the immunostimulatory properties of nucleic acid nanoparticles (NANPs) have demonstrated that variations in the shape, size, and composition lead to distinct patterns in their immunostimulatory properties
Our group has recently reported that biomarkers for NANP immunorecognition are type I and type III interferons (IFNs), which are produced by human primary blood cells only after NANPs are delivered with a widely used lipid-based carrier
Among other structure–activity relationships, we demonstrated that the IFN-inducing capability of NANPs depends on their composition (RNA-based NANPs are more potent than their DNA counterparts), shape

Summary

Introduction

Laboratory for Cancer Research Sponsored by the National Cancer Institute, Frederick, MD 21702, USA; Department of Pharmacology and Therapeutics, Institute of Systems, Molecular and Integrative Biology, Abstract: Recent insights into the immunostimulatory properties of nucleic acid nanoparticles (NANPs) have demonstrated that variations in the shape, size, and composition lead to distinct patterns in their immunostimulatory properties. While most of these studies have used a single lipid-based carrier to allow for NANPs’ intracellular delivery, it is apparent that the platform for delivery, which has historically been a hurdle for therapeutic nucleic acids, is an additional means to tailoring NANP immunorecognition. Our group has recently reported that biomarkers for NANP immunorecognition are type I and type III interferons (IFNs), which are produced by human primary blood cells only after NANPs are delivered with a widely used lipid-based carrier

Methods

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Discussion

Conclusion