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Let $G$ be a torsion-free abelian group of rank two and let $\phi$ be an endomorphism of $G$, called a rank-two \emph{solenoidal endomorphism}. Then it is represented by a $2\times 2$-matrix $M_\phi$ with rational entries. The purpose of this article is to prove the following: The group, $\mathrm{coker}(\phi)$, of the cokernut of $\phi$ is finite if and only if $M_\phi$ is nonsingular, and if it is so, then we give an explicit formula for the order of $\mathrm{coker}(\phi)$, $[G:\mathrm{im}(\phi)]$, in terms of $p$-adic absolute values of the determinant of $M_\phi$. Since $G$ is abelian, the Reidemeister number of $\phi$ is equal to the order of the cokernut of $\mathrm{id}-\phi$ and, when it is finite, it is equal to the number of fixed points of the Pontryagin dual $\widehat\phi$ of $\phi$. Thereby, we solve completely the problem raised in \cite{Miles} of finding the possible sequences of periodic point counts for \emph{all} endomorphisms of the rank-two solenoids.

There has been a growing interest in RNA therapeutics globally, and much progress has been made in this area, which has been further accelerated by the clinical applications of RNA-based vaccines against severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). Following these successful clinical trials, various technologies have been developed to improve the efficacy of RNA-based drugs. Multimerization of RNA therapeutics is one of the most attractive approaches to ensure high stability, high efficacy, and prolonged action of RNA-based drugs. In this review, we offer an overview of the representative approaches for generating repetitive functional RNAs by chemical conjugation, structural self-assembly, enzymatic elongation, and self-amplification. The therapeutic and vaccine applications of engineered multimeric RNAs in various diseases have also been summarized. By outlining the current status of multimeric RNAs, the potential of multimeric RNA as a promising treatment strategy is highlighted.

Herein, we propose innovative deoxyribonucleic acid (DNA)-based gels and their applications in diverse optoelectronics. We prepared the optoelectronic DNA-based gels (supOp/supDNA Gel) through molecular complexation, that is, groove binding and ionic interactions of DNA and 1,1'-diheptyl-4,4'-bipyridinium (DHV). This process is feasible even with sequence-nonspecific DNA extracted from nature (ie.g/i., salmon testes), resulting in the expansion of the application scope of DNA-based gels.supOp/supDNA Gel possessed good mechanical characteristics (ie.g/i., high compressibility, thermoplasticity, and outstanding viscoelastic properties) that have not been observed in typical DNA hydrogels. Moreover, the electrochromic (EC) characteristics of DHV were not lost when combined withsupOp/supDNA Gel. By taking advantage of the facile moldability, voltage-tunable EC behavior, and biocompatibility/biodegradability ofsupOp/supDNA Gel, we successfully demonstrated its applicability in a variety of functional electrochemical systems, including on-demand information coding systems, user-customized EC displays, and microorganism monitoring systems. ThesupOp/supDNA Gel is a promising platform for the application of DNA-based biomaterials in electrochemical optoelectronics.

We derive averaging formulas for the Lefschetz coincidence numbers, the Nielsen coincidence numbers and the Reidemeister coincidence numbers of maps on infra-solvmanifolds modeled on a connected and simply connected solvable Lie group of type (R). As an application, we compare our formula for the Nielsen coincidence numbers with a result of Jezierski (1992) for pairs of maps on some infra-solvmanifolds of Sol. For all pairs of self-maps of a nonorientable infra-solvmanifold of Sol, we determine the sets of all possible values of the Nielsen coincidence numbers and the Reidemeister coincidence numbers.

Advances in the DNA nanotechnology have enabled the fabrication of DNA-based hydrogels with precisely controlled structures and tunable mechanical and biological properties. Compared to DNA hydrogel, preparation of RNA-based hydrogel remains challenging due to the inherent instability of naked RNA. To overcome these limitations, we fabricated a DNA-RNA hybrid hydrogel via stepwise dual enzymatic polymerization. Multimeric short hairpin RNAs (shRNAs) were hybridized with functional DNA aptamers for targeting and mechanical properties of the hydrogel. The obtained DNA-RNA hybrid hydrogel was ultrasoft, robust, and injectable hence reconfigurable into any confined structures. As a model system, the hydrogel was able to mimic microtubule structures under physiological conditions and designed to release the functional small interfering RNA (siRNA)-aptamer complex (SAC) sequentially. In addition, we encoded restriction enzyme-responsive sites in DNA-RNA hybrid hydrogel to boost the release of SAC. This novel strategy provides an excellent platform for systematic RNA delivery through double-controlled release, SAC release from hydrogel, and subsequent release of siRNA from the SAC, which has promising potential in RNA therapy.

Uncontrollable release and unexpected release limit the use of nitric oxide (NO). To overcome this problem, we introduce ZIF-8 as a pH-responsive NO carrier. The flexible framework of ZIF-8 under the high-pressure condition causes the physically NO adsorption inside the SOD cage. ZIF-8 maintain the excellent gas storage ability under the physiological environment. The results show good pH-responsive ability. The gas could not be released out until the particle is in an acid condition. At low pH conditions, half of the gas is released in 1% of the total release duration. Interestingly, the half-release (t1/2) increases to 10% when the phosphate species exist in the acid surrounding. The gradual release can occur under neutral conditions with the existence of phosphate (t1/2 33%). From these results, we expect this ZIF-8 loading NO nanoparticles is lead to the design of innovative gas therapeutic delivery platforms using the advantage of the flexible framework for loading and releasing the gas molecule.

We prove that the growth rate of an endomorphism of a finitely generated nilpotent group is equal to the growth rate of the induced endomorphism on its abelianization, generalizing the corresponding result for an automorphism in [T. Koberda, Entropy of automorphisms, homology and the intrinsic polynomial structure of nilpotent groups, In the Tradition of Ahlfors–Bers. VI, Contemp. Math. 590, American Mathematical Society, Providence 2013, 87–99].

Nanotechnology-based combination therapies, especially chemo-gene therapy, have been spotlighted as promising alternatives for cancer therapy. However, only a small amount of systemically administered nanomedicines reach the tumor site by the enhanced permeability and retention (EPR) effect, resulting in the limited therapeutic efficacy. Furthermore, the design of ideal drug delivery system for chemo-gene therapy has been impeded by the chemical and physical differences between nucleic acids and chemotherapeutics. Herein, we report a precisely designed nanocomplex which exhibits a focused ultrasound (FU)-responsive release and enhanced accumulation of released therapeutics to tumor site. After the nanocomplex composed of siRNA nanoparticles (siRNA-NP) and chemotherapeutics-loaded microbubbles was systemically injected, the nanocomplex was collapsed around the tumor tissue by FU exposure, and both siRNA-NP and chemotherapeutics were penetrated the dense extracellular matrix (ECM) of tumor site, leading to the enhanced chemo-gene therapeutic efficacy. The two-in-one nanocomplex is expected as a promising platform for combination therapy that can enhance the therapeutic efficiency of combination drugs at the cell and/or tissue levels with high drug loading ratio.

From simple 2-dimensional (2D) structures to highly complex 3-dimensional (3D) structures, DNA is widely used as a building block material. Despite this advancement, mass production of DNA nanostructures was a challenge due to the high cost that accompanies the preparation of diverse DNA strands. Rolling circle amplification (RCA) is one of the cost-effective methods for the mass production of repetitive DNA structures without using an expensive laboratory thermal cycler. Here, we report a DNA hydrogel containing various single-stranded DNA nanostructures (Y, X, Tetrahedron) in a one-pot system, prepared by RCA, and their selective separation with various restriction enzymes. Each DNA nanostructure in the DNA hydrogel contained distinctive restriction sites that were responsive to different kinds of restriction enzymes, achieving selective separation of Y-, X- and Tetrahedron-shaped DNA structures. This study has the potential to contribute towards DNA-based biomedical applications by employing mass production and precisely controlled release of DNA nanostructures.

The transdermal delivery of functional biomolecules has been widely achieved by microneedles in a non-invasive manner. However, establishing a simple and universal way to assure a stable loading of a large number of drugs is still imperative, particularly for the delivery of nucleic acid-based drugs. To address this issue, here, we present a universally applicable RNA membrane-coating system as a novel platform to manufacture purpose-oriented microneedles. Customization of RNA membrane-based microneedles is realized by large surface area, high cargo capacity, and controllable material properties of the RNA membrane and 3D-printing of customized scaffold microneedles in a purpose-oriented manner. In addition, simple covering with the RNA membrane facilitates the fabrication of RNA-coated microneedles regardless of the configuration and material of the scaffold. This study demonstrates the successful delivery of RNA along with various types of drugs by purpose-oriented microneedles. Taken together, our approach provides a general route towards the fabrication of tailor-made microneedles for efficient transdermal drug delivery.

DNA has been widely investigated as a carrier for drug delivery. Here, we describe a macroscopic DNA film that has been generated enzymatically. This DNA film was subsequently coated with thrombin (TB) using an aptamer-protein interaction, to expedite hemostasis over a large area. The DNA film coated with TB (DNA patch) significantly improved plasma hemostasis by acting as a coagulative scaffold for TB, as well as carrying localized TB. This study elucidates the benefits of using enzymatic amplification-based DNA structures in the context of topical drug treatment.

Small interference RNA (siRNA) delivery has gained much attention for specific regulation of target protein via RNA interference. However, it has been challenged by inherent instability of naked RNA. To address this issue, a variety of siRNA delivery methods have been developed. The synthesis of RNA nanoparticles (RNPs) by complementary rolling circle transcription (cRCT) has been introduced as a novel route for siRNA delivery, because of the enhanced stability in serum condition and the suitable size for enhanced permeation and retention (EPR) effect. However, RNPs are negatively charged due to the innate structure of RNA, resulting in an inefficient cellular uptake without using transfection agents. In this paper, we report a simple surface modification method of RNP with calcium ion. Calcium-layered RNA nanoparticles (CaRNPs) were generated and used to demonstrate enhanced efficiency of siRNA delivery to HeLa cells in vitro. The results revealed that this simple approach could enhance the cellular uptake efficiency of RNPs in contrast to the naked RNP. Moreover, this method is also applicable for other types of RNAs such as messenger RNA (mRNA), microRNA (miRNA), or single guide RNA (sgRNA), which will greatly enhance therapeutic potential of RNPs.

A coronavirus disease (COVID-19) outbreak associated with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been spreading widely through person-to-person transmission. Various detection approaches have been developed involving quantitative polymerase chain reaction (qPCR) methods, CRISPR-based systems, and direct targeting of specific coronavirus proteins. However, there have only been a few reports on the detection of RNA-dependent RNA polymerase (RdRP), the primer-independent RNA-replicable protein produced by the RNA genes of coronavirus. Here, we introduce a novel diagnostic methodology for COVID-19 using the RNA-directed and de novo RNA replicable function of RdRP. We devised an RNA platform for RdRP-induced transcription (RPRIT) that includes an RNA template that can be directly transcribed by RdRP. By utilizing RPRIT, the presence of RdRP can be readily confirmed within 30 min using isothermal incubation without PCR. This RdRP detection method can provide a new route for rapid diagnosis of RNA virus-infected patients.

A series of new naphthalene diimide (NDI) semiconducting derivatives with different N-phenyl bicyclic side groups were rationally designed and synthesized in this study. The solubility of the orthogonal-shaped NDI derivatives with 5-tetralinyl and 4-indanyl side groups was found to be up to two orders of magnitude higher than that of the linear-shaped NDI derivatives with 6-tetralinyl and 5-indanyl side groups. The orthogonal-shaped NDI derivative with a 5-tetralinyl side group exhibited excellent solution processability due to its high solubility (e.g., 4 g/100 g dichlorobenzene), high thermal stability (e.g., lowest phase transition temperature of 380 °C), and high vertical carrier mobility (e.g., space-current-limited-current electron mobility of 7 × 10−5 cm2/V·s). Therefore, the introduction of N-phenyl bicyclic side groups on organic semiconductors was confirmed to be a highly promising design strategy for achieving the desired physical properties.

Neurons derived from human induced pluripotent stem cells (hiPSCs) are powerful tools for modeling neural pathophysiology and preclinical efficacy/toxicity screening of novel therapeutic compounds. However, human neurons cultured in vitro typically do not fully recapitulate the physiology of the human nervous system, especially in terms of exhibiting morphological maturation, longevity, and electrochemical signaling ability comparable to that of adult human neurons. In this study, we investigated the potential for astrocyte-derived extracellular vesicles (EVs) to modulate survival and electrophysiological function of human neurons in vitro. Specifically, we demonstrate that EVs obtained from human astrocytes promote enhanced single cell electrophysiological function and anti-apoptotic behavior in a homogeneous population of human iPSC-derived cortical neurons. Furthermore, EV-proteomic analysis was performed to identify cargo proteins with the potential to promote the physiological enhancement observed. EV cargos were found to include neuroprotective proteins such as heat shock proteins, alpha-synuclein, and lipoprotein receptor-related protein 1 (LRP1), as well as apolipoprotein E (APOE), which negatively regulates neuronal apoptosis, and a peroxidasin homolog that supports neuronal oxidative stress management. Proteins that positively regulate neuronal excitability and synaptic development were also detected, such as potassium channel tetramerization domain containing 12 (KCTD12), glucose-6- phosphate dehydrogenase (G6PD), kinesin family member 5B (KIF5B), spectrin-alpha non-erythrocytic1 (SPTAN1). The remarkable improvements in electrophysiological function and evident inhibition of apoptotic signaling in cultured neurons exposed to these cargos may hold significance for improving preclinical in vitro screening modalities. In addition, our collected data highlight the potential for EV-based therapeutics as a potential class of future clinical treatment for tackling inveterate central and peripheral neuropathies.

Rolling circle transcription (RCT) has been studied for enhancing the delivery efficiency of therapeutic RNA by densely packing RNA strands with particle formation. This facile fabrication method has been successfully employed to generate RNA nanoballs containing functional short interference RNA. In addition, the nanoballs produced by RCT showed high stability from the nuclease degradation. With these advantages, using biotin-labeled ribonucleoside triphosphate (rNTP), target specific and non-toxic bubble RNA nanoball (BNB) was synthesized. To achieve tumor-targeting, epidermal growth factor receptor antibody (EGFR Ab) was used to target the tumor cells by labeling the target ligands with biotin–avidin interaction. Target gene silencing by EGFR Ab-labeled RNA nanoball was confirmed in vitro. Therefore, RNA nanoball can be utilized for tumor cell-targeting delivery of therapeutic RNA.

USE1 has been demonstrated to play crucial roles in the development and progression of human lung cancer. However, the antitumor efficacy of RNA interference (RNAi) targeting of USE1 has not yet been evaluated as a possible clinical application. We here synthesized USE1 targeting bubbled RNA-based cargo (BRC) composed of densely packed multimeric pre-siRNAs with specific Dicer cleavage sites to enable efficient siRNA release upon entry to target cells. The physical entanglement and continuous networking of RNAs via hybridization during enzymatic replication serve as a driving force for the self-assembly of BRCs. These molecules effectively suppressed the transcription of their target genes, leading to tumor growth suppression in vitro and in vivo. Moreover, their repeated intravenous administration efficiently inhibited the growth of A549 tumor xenografts. Based on these findings of a reduced cancer cell viability following a USE1 knockdown, we further explored cell cycle arrest and apoptosis pathways. The observed tumor cell growth suppression was found to be controlled by cell cycle arrest and apoptosis signals induced by the USE1 reduction. These results suggest that USE1 BRCs may have future clinical applications as an RNAi-based cancer therapy.

Metallic nanoparticle-based probes have been widely developed for cell detection. With the development of nucleic acid technology, the combination of DNA with metallic materials has drawn increased attention. However, the process of conjugating metal nanoparticles to a targeting moiety for sensing applications is inconvenient. We introduce the fabrication of DNA-iron oxide hybrid structures produced by co-precipitation. Using the rolling circle amplification method, highly porous and anionic DNA microsponges are produced. These exhibit numerous active sites for electrostatic interactions with cationic metal salts and produce DNA-templated hybrid structures. Iron oxide nanoparticles were homogeneously synthesized on an individual DNA scaffold without agglomeration. DNA microsponges with concentrated iron oxide nanoparticles exhibit the biological functions of DNA materials, such as cell targeting by aptamers, and can be detected by colorimetric assay via Prussian blue staining.

Under finite regular covering spaces, each preimage class of the base spaces is covered by some preimage classes of the covering spaces. We find an explicit relationship between those preimage classes in terms of covering transformation groups. Thereby we obtain a relationship of the homomorphism indices between them in terms of covering transformation groups. This is a local averaging formula and is the main result of our paper. The local formula gives rise to a global formula for the preimage homomorphism index and a formula for the preimage Reidemeister trace.

Let \({\mathcal {N}}_m\) be the group of \(m\times m\) upper triangular real matrices with all the diagonal entries 1. Then it is an \((m-1)\)-step nilpotent Lie group, diffeomorphic to \({\mathbb {R}}^{\frac{1}{2} m(m-1)}\). It contains all the integer matrices as a lattice \(\Gamma _m\). The automorphism group of \({\mathcal {N}}_m \ (m\ge 4)\) turns out to be extremely small. In fact, \(\mathrm {Aut}({\mathcal {N}})=\mathcal {I} \rtimes \mathrm {Out}({\mathcal {N}})\), where \(\mathcal {I}\) is a connected, simply connected nilpotent Lie group, and \(\mathrm {Out}({\mathcal {N}})={{\tilde{K}}}={(\mathbb {R}^*)^{m-1}\rtimes \mathbb {Z}_2}\). With a nice left-invariant Riemannian metric on \({\mathcal {N}}\), the isometry group is \(\mathrm {Isom}({\mathcal {N}})= {\mathcal {N}} \rtimes K\), where \(K={(\mathbb {Z}_2)^{m-1}\rtimes \mathbb {Z}_2}\subset {{\tilde{K}}}\) is a maximal compact subgroup of \(\mathrm {Aut}({\mathcal {N}})\). We prove that, for odd \(m\ge 4\), there is no infra-nilmanifold which is essentially covered by the nilmanifold \(\Gamma _m\backslash {\mathcal {N}}_m\). For \(m=2n\ge 4\) (even), there is a unique infra-nilmanifold which is essentially (and doubly) covered by the nilmanifold \(\Gamma _m\backslash {\mathcal {N}}_m\).

The cell reprogramming of somatic cells into pluripotent states and subsequent differentiation into certain phenotypes has helped progress regenerative medicine research and other medical applications. Recent research has used viral vectors to induce this reprogramming; however, limitations include low efficiency and safety concerns. In this review, we discuss how biomaterial methods offer potential avenues for either increasing viability and downstream applicability of viral methods, or providing a safer alternative. The use of non-viral delivery systems, such as electroporation, micro/nanoparticles, nucleic acids and the modulation of culture substrate topography and stiffness, has generated valuable insights regarding cell reprogramming.

Age-related macular degeneration (AMD) is the leading cause of blindness in developed countries and is characterized by the development of choroidal neovascularization (CNV). Therapies for AMD have focused on suppressing angiogenic factors, such as vascular endothelial growth factor (VEGF), mainly via conventional anti-VEGF antibody agents. However, additional efforts have been made to develop effective small-interfering RNA (siRNA)-based intracellular therapeutic agents. In this study, we have manufactured a novel siRNA-based anti-VEGF nanoball (siVEGF NB). The siVEGF NB was composed of a siRNA hydrogel with a core of anti-VEGF sequence siRNA coated with branched PEI (bPEI) and hyaluronic acid (HA) in order by applying an electrical force. The novel siVEGF NBs, which were employed in a laser-induced CNV mouse model, were optimized as a retinal and choroidal delivery system through the vitreous humor to the sub-retinal space via CD44 receptor endocytosis on the inner limiting membrane, and showed therapeutic effects via pathways bypassing the TLR3-induced siRNA-class effect. The therapeutic effects of siVEGF NBs lasted for 2 weeks after intravitreal injection showing high targeting efficiency to the sub-retinal space. Thus, the newly developed siVEGF NB may have great potential for the delivery of RNAi-based therapeutics for ocular diseases, including AMD.

3-D integration typically involves multiple chips stacking with large numbers of interconnections within each chip. There are several fundamental technology challenges that need to be addressed in order to realize 3-D integration, such as Cu through-silicon via (TSV) expansion, transistor degradation or open failures on Cu contamination, microbump stress, and so on. The reliability issues on TSV and microbumps are very critical not only for a stacked chip package, but also during wafer-level processes. In this paper, the authors successfully stacked six chips with a thickness of 50 $\mu \text{m}$ and assessed their reliability. Each chip consists of 122054 bumps with a bump diameter of $10~\mu \text{m}$ and a pitch of 20 $\mu \text{m}$ . These bumps were built directly on TSVs, which have a diameter of $5~\mu \text{m}$ . Measured electrical resistance is well matched with calculated electrical resistance. Finally, this paper presents the reliability results of the 3-D IC packages that are embedded in molding compound.

Control of the release properties of drugs has been considered a key factor in the development of drug delivery systems (DDSs). However, drug delivery has limitations including cytotoxicity, low loading efficiency, and burst release. To overcome these challenges, nano or micro-particles have been suggested as carrier systems to deliver chemical drugs. Herein, nano-sized DNA particles (DNAp) were manufactured to deliver netropsin, which is known to bind to DNA minor grooves. The rationally designed particles with exposed rich minor grooves were prepared by DNAp synthesis via rolling circle amplification (RCA). DNAp could load large quantities of netropsin in its minor grooves. An analytical method was also developed for the quantification of netropsin binding to DNAp by UV&ndash, visible spectrometry. Moreover, controlled release of netropsin was achieved by forming a layer of Ca2+ on the DNAp (CaDNAp). As a proof of concept, the sustained release of netropsin by CaDNAp highlights the potential of the DNAp-based delivery approach.

Cells secrete extracellular vesicles (EVs) to external environments to achieve cellular homeostasis and cell-to-cell communication. Their therapeutic potential has been constantly spotlighted since they mirror both cytoplasmic and membranous components of parental cells. Meanwhile, growing evidence suggests that EV engineering could further promote EVs with a maximized capacity. In this review, a range of engineering techniques as well as upscaling approaches to exploit EVs and their mimetics are introduced. By laying out the pros and cons of each technique from different perspectives, we sought to provide an overview potentially helpful for understanding the current state of the art EV engineering and a guideline for choosing a suitable technique for engineering EVs. Furthermore, we envision that the advances in each technique will give rise to the combinatorial engineering of EVs, taking us a step closer to a clinical translation of EV-based therapeutics.

We report a novel approach for generating nanosized DNA hollow spheres (HSs) using enzymatically produced DNA microsponges in a self-templating manner. In previous studies, preparation of DNA nanostructures with specified functions required multiple complicated steps. In this study, however, a simple treatment with the nucleophilic agent 4-dimethylaminopyridine (DMAP) enabled a gradual disentanglement of DNA in microsponges by electrostatic interactions between DMAP and DNA, and the DNA underwent a reassembly process to generate hollow shell structures without denaturation/annealing by thermal cycling. In addition, this synthetic process was conducted in a water-based system without organic solvents, enabling the synthesis of biologically and environmentally friendly products. Based on the benefits of hollow shell structures, which include their high surface-to-volume ratio and ability to encapsulate small molecules, we envision that this simple approach for synthesizing DNA HSs will provide a new platform for maximizing their potential use in drug delivery and bio-imaging.

Let M be a nilmanifold modeled on the standard filiform Lie group \(\mathcal {H}_{m+1}\) and let \(f:M\rightarrow M\) be a self-map. Using the averaging formulas, we compute the spectra of the Lefschetz, Nielsen, and Reidemeister (coincidence) numbers of maps f on M. Moreover, we give explicit formulas for a complete computation of the Nielsen type numbers \(N\mathrm {P}_n(f)\) and \(N\!\Phi _n(f)\). We also give a complete description of the sets of homotopy minimal periods of all such maps on M.

The development of RNA self-assemblies offers a powerful platform for a wide range of biomedical applications. The fabrication process has become more elaborate in order to achieve functional structures with maximized potential. As a facile means to control the structure, here, we report a new approach to manipulate the polymerization rate and subsequent self-assembly process through regulation of the reaction viscosity. As the RNA polymerization rate has a dependence on solution viscosity, the resulting assembly, crystallization, and overall sizes of the product could be manipulated. The simple and precise control of RNA polymerization and self-assembly by reaction viscosity will provide a way to widen the utility of RNA-based materials.

RNA interference (RNAi)-based gene therapy has drawn tremendous attention due to its highly specific gene regulation by selective degradation of any target mRNA. There have been multiple reports regarding the development of various cationic materials for efficient siRNA delivery, however, many studies still suffer from the conventional delivery problems such as suboptimal transfection performance, a lack of tissue specificity, and potential cytotoxicity. Despite the huge therapeutic potential of siRNAs, conventional gene carriers have failed to guarantee successful gene silencing in vivo, thus not warranting clinical trials. The relatively short double-stranded structure of siRNAs has resulted in uncompromising delivery formulations, as well as low transfection efficiency, compared with the conventional nucleic acid drugs such as plasmid DNAs. Recent developments in structural siRNA and RNAi nanotechnology have enabled more refined and reliable in vivo gene silencing with multiple advantages over naked siRNAs. This review focuses on recent progress in the development of structural DNA/RNA-based RNAi systems and their potential therapeutic applications. In addition, an extensive list of prior reports on various RNAi systems is provided and categorized by their distinctive molecular characters.

Nucleic acid-based therapeutics are being used increasingly for biomedical applications. Despite this, the development of nontoxic and cell-targetable delivery systems for practical use is still a challenge. This paper reports a novel enzymatic synthetic approach to produce cell-targetable RNA nanovectors. The RNA nanovectors were generated by the hybridization of DNA and RNA strands produced by temperature-dependent dual polymerization, which is also called stepwise dual enzyme polymerization. The RNA strands are designed to contain siRNA precursors, and the DNA strands include aptamers that bind specifically to the target molecules for cell-targeting. The RNA nanovector can also enhance the resistance to nuclease degradation and help overcome the limitations associated with the nature of RNA via DNA-RNA hybrids. Therefore, the proposed strategy, stepwise dual enzyme polymerization, is an innovative solution for successful carrier-free siRNA delivery.

First published online by Duke University Press 15 January 2010, subsequently published online by Cambridge University Press 11 January 2016, doi:10.1017/S0027763000009818

Here, we synthesized DNA microparticles comprised of thrombin binding aptamers via rolling circle amplification (RCA). These DNA aptamer particles could successfully load a number of thrombins and the complexes have shown improved thrombin activity. This new platform offers a protein loading and delivery system for medical applications.