Modulating Immune Response with Nucleic Acid Nanoparticles

Abstract

Nano-objects made of nucleic acids are becoming promising materials in the biomedical field. This is, in part, due to DNA and RNA self-assembly properties that can be accurately computed to fabricate various complex nanoarchitectures of 2D and 3D shapes. The nanoparticles can be assembled from DNA, RNA, and chemically modified oligonucleotide mixtures which, in turn, influence their chemical and biophysical properties. Solid-phase synthesis allows large-scale production of individual oligonucleotide strands with batch-to-batch consistency and exceptional purity. All of these advantageous characteristics of nucleic-acid-based nanoparticles were known to be exceptionally useful as a nanoplatform for drug delivery purposes. Recently, several important discoveries have been achieved, demonstrating that nucleic acid nanoparticles (NANPs) can also be used to modulate the immune response of host cells. The purpose of this review is to briefly overview studies demonstrating architectural design principles of NANPs, as well as the ability of NANPs to control immune responses.

DNA‐Based Nanoarchitectures as Eminent Vehicles for Smart Drug Delivery Systems

“…Immunotherapy is a methodology to treat diseases through the promotion of native immune system of the body, and is characterized by low side effects and high specificity. [228,229] It is now well known that cytidine-phosphate-guanosine sequences (CpG) in DNA bind to Toll-like receptors, and elicit a strong systemic immune reaction. [230][231][232] With the use of a cyclic template involving many CpG sequences on rolling circle amplification (RCA), DNA nano-cocoon for cancer immunotherapy was prepared.…”

Improved Nucleic Acid Therapy with Advanced Nanoscale Biotechnology

“…193,194 The unmethylated cytosine-phosphate-guanosine (CpG) oligodeoxynucleotides (ODNs) is known as an immunostimulant. [195][196][197] The size and shape have been reported to play vital roles in pharmacokinetic profile and biodistribution of NPs. Compared with RNA monomers, locally administered compact RNA globular structures with intramolecular connectivity induced more interferon (IFN) production.…”

“…193 This means that by adjusting the assembling of NAs and introducing nanoscaffolds, the desirable immunostimulatory effects or undesirable immunostimulation could be fine-tuned. 196,197 Taken together, since NANPs can be designed and programmed to exhibit no, low, or high immunostimulation, their application should not be limited by immunotoxicity.…”

Nucleic Acid Nanostructure Assisted Immune Modulation

“…29 Among the many different types of nanomaterials explored for delivering nucleic acids, the programmable nucleic acidbased nanostructures are emerging as unique and novel materials to modulate the immune reactions. 17, 30,31 The unique self-assembling characteristics of nucleic acids are attractive in using them as building materials for higher ordered nanostructures. 32−34 In fact, nucleic acids, especially DNA, are excellent building blocks in constructing threedimensional nanostructures with unprecedent complexity and precision over size, shape, and valency.…”

“…Among the many different types of nanomaterials explored for delivering nucleic acids, the programmable nucleic acid-based nanostructures are emerging as unique and novel materials to modulate the immune reactions. ,, The unique self-assembling characteristics of nucleic acids are attractive in using them as building materials for higher ordered nanostructures. − In fact, nucleic acids, especially DNA, are excellent building blocks in constructing three-dimensional nanostructures with unprecedent complexity and precision over size, shape, and valency. Particularly, recent studies demonstrated that nucleic acid-based nanostructures can overcome multiple biological and molecular barriers associated with delivering the unformulated nucleic acids. , Here we review the recent studies in the design of nucleic acid nanostructures for immune system modulation.…”