Triggering RNAi with multifunctional RNA nanoparticles and their delivery

Abstract

in the bloodstream, poor cellular uptake, and inefficient intracellular release. In an attempt to solve these issues, different types of RNAi therapeutic delivery strategies including multifunctional RNA nanoparticles are being developed. In this mini-review, we will briefly describe some of the current approaches.Keywords: RNA nanotechnology, RNA nanoparticles, RNA/DNA hybrids, RNA interference, siRNA, delivery IntroductionAccording to the Social Security Administration, average Americans that reach age 65 today most likely will live to be 84 years old [1]. However, with older age, the chances of contracting deadly diseases, such as cancer, increases dramatically. Some cancers (e.g. breast cancer) can be removed surgically but this does not guarantee that the disease will not return within a patient's lifetime. For other types of cancer (e.g. chronic lymphocytic leukemia), surgery may have very little effect (http://www. cancer.org). Other available treatments are chemo-and immunotherapies. However, these alternatives lack target specificity and cause severe toxic side effects affecting the growth of hair, nails, loss of appetite and blood cell count, just to name a few (http://www.cancer.org). Therefore, the advancements in biomedical technologies that provide safe and effective cancer treatment are in demand. Among the novel approaches is the recognition and use of specific intracellular RNA signatures (e.g. an overexpression of certain genes) that are especially important in detection and personalized treatments of cancers as well as viral infections, and autoimmune diseases [2][3][4]. The wide use of novel therapeutics based on target specific RNA-mediated gene silencing, called RNA interference or RNAi, will likely become the next breakthrough in cancer therapy. The first successful therapeutic knockdown of the endogenous gene, apolipoprotein B (ApoB), occurred in a 2004 study [5], only a few years after the original discovery of RNAi [6]. In 2010, DOI 10.1515/rnan-2015-0001 Received April 6, 2015 accepted May 6, 2015 Abstract: Proteins are considered to be the key players in structure, function, and metabolic regulation of our bodies. The mechanisms used in conventional therapies often rely on inhibition of proteins with small molecules, but another promising method to treat disease is by targeting the corresponding mRNAs. In 1998, Craig Mellow and Andrew Fire discovered dsRNA-mediated gene silencing via RNA interference or RNAi. This discovery introduced almost unlimited possibilities for new gene silencing methods, thus opening new doors to clinical medicine. RNAi is a biological process that inhibits gene expression by targeting the mRNA. RNAi-based therapeutics have several potential advantages (i) a priori ability to target any gene, (ii) relatively simple design process, (iii) sitespecificity, (iv) potency, and (v) a potentially safe and selective knockdown of the targeted cells. However, the problem lies within the formulation and delivery of RNAi therapeutics including rapid excretion, instab...

Toll-Like Receptor-Mediated Recognition of Nucleic Acid Nanoparticles (NANPs) in Human Primary Blood Cells

“…Nucleic acid nanoparticles (NANPs) have recently evolved as an innovative type of therapeutic in which RNA and/or DNA strands serve as the basis for constructing novel nanomaterials, generating limitless possibilities of novel bottom-up nanoarchitectures [8,9,10,11,12,13,14,15,16]. Unlike other nanocarriers [17], NANPs have unique properties which create a niche for these materials in the current biomedical field.…”

RNA–DNA fibers and polygons with controlled immunorecognition activate RNAi, FRET and transcriptional regulation of NF-κB in human cells

“…Although up to seven active siRNAs can be released from a single pair of hybrids, the resulting byproduct—long dsDNAs—becomes immunostimulatory (14). We could avoid the formation of long dsDNAs while still maintaining a higher number of split functionalities by embedding up to six hybrids in various RNA and DNA nanoparticles and mixing them with cognate hybrids (15,28,29,31). This technique, however, requires the simultaneous presence of seven assemblies and may be inefficient due to potential problems with intracellular compartmentalization.…”

The immunorecognition, subcellular compartmentalization, and physicochemical properties of nucleic acid nanoparticles can be controlled by composition modification

“…NANPs can be engineered to perform a variety of therapeutic and diagnostic functions due to the natural biological roles of RNA and DNA ( 1 , 2 , 11 , 15 , 31 , 32 ). However, the transition of NANPs to clinical use has been limited due to issues regarding production, chemical instability, intracellular delivery and off-target stimulation of the immune system ( 12 , 33 , 34 ).…”