Kirill A Afonin

Kirill A Afonin
University of North Carolina at Charlotte | UNC Charlotte · Department of Chemistry I afoninlab.com

PhD

About

125
Publications
12,626
Reads
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2,858
Citations
Additional affiliations
July 2019 - present
University of North Carolina at Charlotte
Position
  • Professor (Associate)
January 2011 - December 2014
NCI-Frederick
Position
  • Research Associate
January 2011 - December 2014
National Cancer Institute (USA)
Position
  • Research Associate

Publications

Publications (125)
Preprint
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) surface spike glycoprotein - a major antibody target - is critical for virus entry via engagement of human angiotensin-converting enzyme 2 (ACE2) receptor. Despite successes with existing vaccines and therapies that primarily target the receptor binding domain (RBD) of the spike protein,...
Article
RNA fibers are a class of biomaterials that can be assembled using HIV-like kissing loop interactions. Because of the programmability of molecular design and low immunorecognition, these structures present an interesting opportunity to solve problems in nanobiotechnology and synthetic biology. However, the experimental tools to fully characterize a...
Article
Recent advances in nanotechnology now allow for the methodical implementation of therapeutic nucleic acids (TNAs) into modular nucleic acid nanoparticles (NANPs) with tunable physicochemical properties which can match the desired biological effects, provide uniformity, and regulate the delivery of multiple TNAs for combinatorial therapy. Despite th...
Article
Poly(ethylene glycol) or PEG has a long history of use in medicine. Many conventional formulations utilize PEG as either an active ingredient or an excipient. PEG found its use in biotechnology therapeutics as a tool to slow down drug clearance and shield protein therapeutics from undesirable immunogenicity. Nanotechnology field applies PEG to crea...
Article
With numerous recent advances, the field of therapeutic nucleic acid nanotechnology is now poised for clinical translation supported by several examples of FDA-approved nucleic acid nanoformulations including two recent mRNA-based COVID-19 vaccines. Within this rapidly growing field, a new subclass of nucleic acid therapeutics called nucleic acid n...
Article
The International Society of RNA Nanotechnology and Nanomedicine (ISRNN) hosts an annual meeting series focused on presenting the latest research achievements involving RNA-based therapeutics and strategies, aiming to expand their current biomedical applications while overcoming the remaining challenges of the burgeoning field of RNA nanotechnology...
Article
Precise control over the assembly of biocompatible three-dimensional (3D) nanostructures would allow for programmed interactions within the cellular environment. Nucleic acids can be used as programmable crosslinkers to direct the assembly of quantum dots (QDs) and tuned to demonstrate different interparticle binding strategies. Morphologies of sel...
Article
Full-text available
The relatively straightforward methods of designing and assembling various functional nucleic acids into nanoparticles offer advantages for applications in diverse diagnostic and therapeutic approaches. However, due to the novelty of this approach, nucleic acid nanoparticles (NANPs) are not yet used in the clinic. The immune recognition of NANPs is...
Article
Full-text available
Silver has a long history of antibacterial effectiveness. The combination of atomically precise metal nanoclusters with the field of nucleic acid nanotechnology has given rise to DNA-templated silver nanoclusters (DNA-AgNCs) which can be engineered with reproducible and unique fluorescent properties and antibacterial activity. Furthermore, cytosine...
Article
Contractile forces within the planar interface between T cell and antigen-presenting surface mechanically stimulate T cell receptors (TCR) in the mature immune synapses. However, the origin of mechanical stimulation during the initial, i.e., presynaptic, microvilli-based TCR activation in the course of immune surveillance remains unknown and new to...
Article
With recent advances in nanotechnology and therapeutic nucleic acids (TNAs), various nucleic acid nanoparticles (NANPs) have demonstrated great promise in diagnostics and therapeutics. However, the full realization of NANPs’ potential necessitates the development of a safe, efficient, biocompatible, stable, tissue-specific, and non-immunogenic deli...
Article
Radiation induces the generation of Platelet-activating factor receptor (PAF-R) ligands, including PAF and oxidized phospholipids. Alternatively, PAF is also synthesized by the biosynthetic enzymes lysophosphatidylcholine acyltransferases (LPCATs) which are expressed by tumor cells including melanoma. The activation of PAF-R by PAF and oxidized lip...
Article
Nucleic acid nanoparticles (NANPs) represent a highly versatile molecular platform for the targeted delivery of various therapeutics. However, despite their promise, further clinical translation of this innovative technology can be hindered by immunological off-target effects. All human cells are equipped with an arsenal of receptors that recognize...
Article
Full-text available
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 ap...
Article
Full-text available
Nucleic acid nanoparticles (NANPs) have become powerful new platforms as therapeutic and diagnostic tools due to the innate biological ability of nucleic acids to identify target molecules or silence genes involved in disease pathways. However, the clinical application of NANPs has been limited by factors such as chemical instability, inefficient i...
Article
This protocol assesses proinflammatory properties of nucleic acid nanoparticles (NANPs) using a validated preclinical model, peripheral blood mononuclear cells (PBMCs), that is highly predictive of cytokine responses. The experimental procedure details the preparation of pyrogen-free NANPs, isolation of PBMCs from freshly collected human blood, and...
Article
Programmable nucleic acid nanoparticles (NANPs) with precisely controlled functional compositions can regulate the conditional activation of various biological pathways and responses in human cells. However, the intracellular delivery of NANPs alone is hindered by their susceptibility to nuclease activity and inefficient crossing of biological memb...
Article
Full-text available
RNAi-based therapeutics have shown biomedical potential; however, safe and efficient delivery of RNA remains a barrier for clinical applications. Nucleic acid-based nanoparticles (NANPs) programmed to self-assemble into structures with multiple therapeutic nucleic acids (TNAs) are attractive for therapeutics, especially the ability to manipulate th...
Article
Recent clinical successes using therapeutic nucleic acids (TNAs) have accelerated the transition of nucleic acid nanotechnology toward therapeutic applications. Significant progress in the development, production, and characterization of nucleic acid nanomaterials and nucleic acid nanoparticles (NANPs), as well as abundant proof-of-concept data, ar...
Article
Combining atomically resolved DNA-templated silver nanoclusters (AgNCs) with nucleic acid nanotechnology opens new exciting possibilities for engineering bioinorganic nanomaterials with uniquely tunable properties. In this unforeseen cooperation, nucleic acids not only drive the formation of AgNC but also promote their spatial organization in supra...
Article
Communicating the flow of genetic information (DNA → RNA → protein) is not only a basis of biochemical education, but also is the essential foundation for understanding the complexity of biological processes. The described laboratory exercise demonstrates that the information encoded into different DNA sequences can be transformed into various silv...
Article
Nucleic acids have been utilized to construct an expansive collection of nanoarchitectures varying in design, physicochemical properties, cellular processing and biomedical applications. However, the broader therapeutic adaptation of nucleic acid nanoassemblies in general, and RNA-based nanoparticles in particular, have faced several challenges in...
Article
Full-text available
Background: Bacterial meningitis and meningoencephalitis are associated with devastating neuroinflammation. We and others have demonstrated the importance of glial cells in the initiation of immune responses to pathogens invading the central nervous system (CNS). These cells use a variety of pattern recognition receptors (PRRs) to identify common...
Article
Full-text available
Small interfering RNAs (siRNAs) are potential therapeutic substances due to their gene silencing capability as exemplified by the recent FDA’s approval of the first siRNA therapeutic agent (Patisiran). However, the delivery of naked siRNAs is challenging because of their short plasma half-lives and poor cell penetrability. In this study, we used ve...
Article
The unknown immune stimulation by nucleic acid nanoparticles (NANPs) has become one of the major impediments to a broad spectrum of clinical developments of this novel technology. Having evolved to defend against bacterial and viral nucleic acids, mammalian cells have established patterns of recognition that are also the pathways through which NANP...
Article
Programmable nucleic acid nanoparticles (NANPs) provide controlled coordination of therapeutic nucleic acids (TNAs) and other biological functionalities. Beyond multivalence, recent reports demonstrate that NANP technology can also elicit a specific immune response, adding another layer of customizability to this innovative approach. While the deli...
Article
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The use of nucleic acids (RNA and DNA) offers a unique and multifunctional platform for numerous applications including therapeutics, diagnostics, nanodevices, and materials [...]
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Nucleic acid-based technologies are an emerging research focus area for pharmacological and biological studies because they are biocompatible and can be designed to produce a variety of scaffolds at the nanometer scale. The use of nucleic acids (ribonucleic acid (RNA) and/or deoxyribonucleic acid (DNA)) as building materials in programming the asse...
Article
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Besides being a passive carrier of genetic information, DNA can also serve as an architecture template for the synthesis of novel fluorescent nanomaterials that are arranged in a highly organized network of functional entities such as fluorescent silver nanoclusters (AgNCs). Only a few atoms in size, the properties of AgNCs can be tuned using a var...
Article
Full-text available
Nucleic acids are programmable and biocompatible polymers that have beneficial uses in nanotechnology with broad applications in biosensing and therapeutics. In some cases, however, the development of the latter has been impeded by the unknown immunostimulatory properties of nucleic acid-based materials, as well as a lack of functional dynamicity d...
Article
Full-text available
Infusion reactions (IRs) create a translational hurdle for many novel therapeutics, including those utilizing nanotechnology. Nucleic acid nanoparticles (NANPs) are a novel class of therapeutics prepared by rational design of relatively short oligonucleotides to self-assemble into various programmable geometric shapes. While cytokine storm, a commo...
Article
Multifunctional hybrid nanoparticles are being developed to carry a wide variety of therapeutic and imaging agents for multiple biomedical applications. Polysilsesquioxane (PSilQ) nanoparticles is a promising hybrid platform with numerous advantages to be used as delivery system. In this report, we demonstrate the ability of a stimuli-responsive PS...
Article
Full-text available
Nucleic acid-based assemblies that interact with each other and further communicate with the cellular machinery in a controlled manner represent a new class of reconfigurable materials that can overcome limitations of traditional biochemical approaches and improve the potential therapeutic utility of nucleic acids. This notion enables the developme...
Article
Full-text available
RNA aptamers selected to bind fluorophores and activate their fluorescence offer a simple and modular way to visualize native RNAs in cells. Split aptamers which are inactive until the halves are brought within close proximity can become useful for visualizing the dynamic actions of RNA assemblies and their interactions in real time with low backgr...
Article
Full-text available
RNA is a versatile biomaterial that can be used to engineer nanoassemblies for personalized treatment of various diseases. Despite promising advancements, the design of RNA nanoassemblies with minimal recognition by the immune system remains a major challenge. Here, an approach is reported to engineer RNA fibrous structures to operate as a customiz...
Article
RNA is now widely acknowledged not only as a multifunctional biopolymer but also as a dynamic material for constructing nanostructures with various biological functions. Programmable RNA nanoparticles (NPs) allow precise control over their formulation and activation of multiple functionalities, with the potential to self-assemble in biological syst...
Article
RNA is now widely acknowledged not only as a multifunctional biopolymer but also as a dynamic material for constructing nanostructures with various biological functions. Programmable RNA nanoparticles (NPs) allow precise control over their formulation and activation of multiple functionalities, with the potential to self-assemble in biological syst...
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Full-text available
With the advancement of ribonucleic acid (RNA) research in the field of biochemistry, ensuring that undergraduate students have both the theoretical and practical knowledge of current, cutting-edge experimental techniques is of marked importance. Many current biochemistry experiments demonstrate various basic molecular biological techniques includi...
Article
Nucleic acid nanoparticles (NANPs) have evolved as a new class of therapeutics with the potential to detect and treat diseases. Despite tremendous advancements in NANPs’ development, their immunotoxicity, one of the major impediments in clinical translation of traditional therapeutic nucleic acids (TNAs), has never been fully characterized. Here, w...
Chapter
According to the WHO, we can expect the rise of around 24 million new cases of cancer per year by around 2030 worldwide, which is a 70% increase from 2012. The molecular key players leading to cancer are heterogeneous in respect to tissue origin and may vary from patient to patient, calling for an individualized approach. Nucleic acid biopolymers (...
Article
RNA is an attractive biopolymer for engineering self-assembling materials suitable for biomedical applications. Previously, programmable hexameric RNA rings were developed for the controlled delivery of up to six different functionalities. To increase the potential for functionalization with little impact on nanoparticle topology, we introduce gaps...
Article
When light is used to excite electronic transitions in a material, non-radiative energy during relaxation is often released in the form of heat. In this work, we show that photoexcitation of a silicon nitride nanopore using a focused visible laser results in efficient localized photothermal heating, which reduces the nearby electrolyte viscosity an...
Article
In the past few years, the study of therapeutic RNA nanotechnology has expanded tremendously to encompass a large group of interdisciplinary sciences. It is now evident that rationally designed programmable RNA nanostructures offer unique advantages in addressing contemporary therapeutic challenges such as distinguishing target cell types and ameli...
Article
Nucleic acid nanoparticles (NANPs) are an emerging class of programmable structures with tunable shape and function. Their promise as tools for fundamental biophysics studies, molecular sensing, and therapeutic applications, necessitates methods for their detection and characterization at the single-particle level. In this work, we study electropho...
Chapter
RNA nanoparticles consisting of multiple RNA strands of different sequences forming various three-dimensional structures emerge as promising carriers of siRNAs, RNA aptamers, and ribozymes. In vitro transcription of a mixture of dsDNA templates encoding all the subunits of the RNA nanoparticle may result in cotranscriptional self-assembly of the na...
Chapter
Human immunodeficiency virus Type 1 (HIV-1) is the major cause of acquired immune deficiency syndrome (AIDS). In 2014, it was estimated that 1.2 million people died from AIDS-related illnesses. RNA interference-based therapy to block HIV replication is a field that, as of now, is without any FDA-approved drugs available for clinical use. In this ch...
Chapter
RNA has gained great interest for use in biomedical and therapeutic applications. This is due in part to RNA’s ability to perform multiple functions, including the regulation of endogenously expressed genes. However, the ability of RNA based drugs to distinguish target diseased cells from healthy tissue remains challenging. Here we present methods...
Article
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Correction for 'Programmable RNA microstructures for coordinated delivery of siRNAs' by Jaimie Marie Stewart et al., Nanoscale, 2016, 8, 17542-17550.
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We introduce a new concept that utilizes cognate nucleic acid nanoparticles which are fully complementary and functionally-interdependent to each other. In the described approach, the physical interaction between sets of designed nanoparticles initiates a rapid isothermal shape change which triggers the activation of multiple functionalities and bi...
Article
RNA nanotechnology employs synthetically modified ribonucleic acid (RNA) to engineer highly stable nanostructures in one, two, and three dimensions for medical applications. Despite the tremendous advantages in RNA nanotechnology, unmodified RNA itself is fragile and prone to enzymatic degradation. In contrast to use traditionally modified RNA stra...
Article
The targeted and conditional activation of pharmaceuticals is an increasingly important feature in modern personalized medicine. Nucleic acid nanoparticles show tremendous potential in this exploit due to their programmability and biocompatibility. Among the most powerful nucleic acid specific treatments is RNA interference-based therapeutics. RNA...
Article
We demonstrate the first biosensing strategy that relies on quantum dot (QD) fluorescence blinking to report the presence of a target molecule. Unlike other biosensors that utilize QDs, our method does not require the analyte to induce any fluorescence intensity or color changes, making it readily applicable to a wide range of target species. Inste...
Article
RNA is a natural multifunctional polymer, and is an essential component in both complex pathways and structures within the cellular environment. For this reason, artificial self-assembling RNA nanostructures are emerging as a powerful tool with broad applications in drug delivery and metabolic pathway regulation. To date, coordinated delivery of fu...
Article
RNA nanostructures have capabilities to simultaneously incorporate different defined functions, such as specific binding to a ligand, or programmable regulation of gene expression. Self-assembling nanostructures containing functional RNAs provide further options for nanobiology applications. This review is focused on four growing lists of importanc...
Article
Designing self-assembling RNA ring structures based on known 3D structural elements connected via linker helices is a challenging task due to the immense number of motif combinations, many of which do not lead to ring-closure. We describe an in silico solution to this design problem by combinatorial assembly of RNA 3-way junctions, bulges, and kiss...
Article
Current work reports the use of single-stranded RNA toeholds of different lengths to promote the reassociation of various RNA-DNA hybrids, which results in activation of multiple split functionalities inside human cells. The process of reassociation is analyzed and followed with a novel computational multistrand secondary structure prediction algor...
Article
RNA is an attractive material for the creation of molecular logic gates that release programmed functionalities only in the presence of specific molecular interaction partners. Here we present HyperFold, a multistrand RNA/DNA structure prediction approach for predicting nucleic acid complexes that can contain pseudoknots. We show that HyperFold als...
Article
Our research on nucleic acids-based functional nanostructures includes computational design, modeling and characterization of their dynamic behavior. Computational simulations also include characterization of the delivery agents, complementing the in vitro and in vivo experiments. siRNAs capable of knocking down genes of interest in cancer cells, f...
Article
Recently, we developed a novel technique based on RNA/DNA hybrid reassociation that allows conditional activation of different split functionalities inside diseased cells and in vivo. We further expanded this idea to permit simultaneous activation of multiple different functions in a fully controllable fashion. In this chapter, we discuss some nove...
Article
In this study we have investigated a new class of cationic lipids - "bolaamphiphiles" or "bolas" for their ability to efficiently deliver small interfering RNAs (siRNAs) to cancer cells. The bolas of this study consist of a hydrophobic chain with one or more positively charged head groups at each end. Recently, we reported that micelles of the bola...