Abstract: A conductive channel-containing membrane includes a membrane layer, and a SPP1 connector polypeptide variant that is incorporated into the membrane layer to form an aperture through which conductance can occur when an electrical potential is applied across the membrane. A method of sensing a molecule, such as a polypeptide or nucleic acid molecule, makes use of the conductive channel-containing membrane. A method of DNA sequence makes use of the conductive channel-containing membrane.

Abstract: Disclosed herein are compositions comprising extracellular vesicles, such as exosomes, displaying an RNA nanoparticle on its surface. The RNA nanoparticle can target the extracellular vesicle to a given cell via a targeting moiety. The extracellular vesicle can also comprise a functional moiety, which can be used in treatment or diagnostics.

Abstract: The presently-disclosed subject matter relates to an artificial RNA nanostructure molecule and method to treat brain tumor in a subject. More particularly, the presently disclosed subject matter relates to a RNA nanostructure containing a multiple branched RNA nanoparticle, a brain tumor targeting module, and an effective amount of a therapeutic agent. Further, the presently disclosed subject matter relates to a method of using the RNA nanostructure composition to treat brain tumor in a subject having or at risk of having brain tumor.

Abstract: The present invention is directed towards an artificial RNA nanostructure comprising multiple external strands of RNA, each external strand comprising about 40-50 nucleotides; one internal strand of RNA comprising more than about 50 nucleotides; the internal strands and external strands assembled to form a triangle nanostructure, a square nanostructure, or a polygon nanostructure and a pRNA three-way junction (3WJ) motif at each vertex of the nanostructure. Such nanostructure can be provided in a composition together with an adjuvant for use in inducing the production of high affinity neutralizing antibodies or inhibitory antibodies, inducing the production of cytokines, inducing an immune response in a subject, or a combination thereof.

Abstract: RNA nanoparticles functionalized with a HER2-targeting RNA aptamer and at least one MED1 siRNA for targeted delivery of MED1 siRNA to human cancer cells via human epidermal growth factor receptor 2 (HER2) receptors, pharmaceutical compositions of the inventive RNA nanoparticles, and methods for treating breast, HER2-implicated cancers, and in particular therapeutic-resistant cancer such as tamoxifen-resistant breast cancer, by administering pharmaceutical compositions of the inventive RNA nanoparticles.

Abstract: The present invention is directed towards an artificial RNA nanostructure comprising multiple external strands of RNA, each external strand comprising about 40-50 nucleotides; one internal strand of RNA comprising more than about 50 nucleotides; the internal strands and external strands assembled to form a triangle nanostructure, a square nanostructure, or a polygon nanostructure and a pRNA three-way junction (3WJ) motif at each vertex of the nanostructure. Such nanostructure can be provided in a composition together with an adjuvant for use in inducing the production of high affinity neutralizing antibodies or inhibitory antibodies, inducing the production of cytokines, inducing an immune response in a subject, or a combination thereof.

Abstract: Disclosed herein are three-dimensional cage molecules, wherein the cage molecule is composed of RNA. Also disclosed is a composition including the three-dimensional cage molecule, as well as a pharmaceutical composition containing the three-dimensional cage molecule. Also disclosed herein are methods of administering a cage molecule, composition, or formulation thereof to a subject in need thereof.

Abstract: The presently-disclosed subject matter relates to RNA-based composition and method to treat breast cancer in a subject. More particularly, the presently disclosed subject matter relates to a RNA nanostructure and composition containing a multiple branched RNA nanoparticle, a breast cancer targeting module, and an effective amount of a breast cancer therapeutic agent. Further, the presently disclosed subject matter relates to a method of using the RNA nanoparticle composition to treat breast cancer in a subject having or at risk of having breast cancer.

Abstract: The presently-disclosed subject matter relates to an artificial RNA nanostructure molecule and method to treat brain tumor in a subject. More particularly, the presently disclosed subject matter relates to a RNA nanostructure containing a multiple branched RNA nanoparticle, a brain tumor targeting module, and an effective amount of a therapeutic agent. Further, the presently disclosed subject matter relates to a method of using the RNA nanostructure composition to treat brain tumor in a subject having or at risk of having brain tumor.

Abstract: Disclosed herein are RNA nanopores that can be used for single molecule sensing, disease diagnosis, and even protein sequencing.

Abstract: The presently-disclosed subject matter relates to an engineered T3 or T4 viral DNA-packaging motor connector protein that can be incorporated into a lipid membrane to form an electroconductive aperture, and which can be provided for other uses described herein.

Abstract: The presently-disclosed subject matter relates to RNA-based composition and method to treat gastric cancer in a subject. More particularly, the presently disclosed subject matter relates to a RNA nanostructure and composition containing a multiple branched RNA nanoparticle, a gastric cancer targeting module, and an effective amount of a therapeutic agent. Further, the presently disclosed subject matter relates to a method of using the RNA nanoparticle composition to treat gastric cancer in a subject having or at risk of having gastric cancer.

Abstract: Disclosed herein are compositions comprising extracellular vesicles, such as exosomes, displaying an RNA nanoparticle on its surface. The RNA nanoparticle can target the extracellular vesicle to a given cell via a targeting moiety. The extracellular vesicle can also comprise a functional moiety, which can be used in treatment or diagnostics.

Abstract: A method is described for the identification of multi-subunit biocomplex drug targets. The method includes identifying a target that performs a biological function, wherein the target comprises one or more subunits, wherein a minimum number of the one or more subunits is inactivated to inhibit the biological function. The method includes selecting a drug that binds specifically to each subunit of the one or more subunits with a target probability. The method describes a relationship between inhibition efficiency of the drug and total number of the one or more subunits using a binomial distribution, wherein the inhibition efficiency comprises a probability that the delivered drug blocks the biological function. The method includes confirming empirically the relationship using an experimental target. The method includes administering the drug to the target to treat a multi-drug resistant disease, wherein the target comprises a biological complex in a mammalian subject.

Abstract: The presently-disclosed subject matter relates to an artificial RNA nanostructure and method of use thereof. In particular, the presently-disclosed subject matter relates to RNA nanoparticles and RNA dendrimers, and methods of disease diagnosis and treatments using the RNA nanostructure and RNA dendrimers.

Abstract: A conductive channel-containing membrane includes a membrane layer, and a SPP1 connector polypeptide variant that is incorporated into the membrane layer to form an aperture through which conductance can occur when an electrical potential is applied across the membrane. A method of sensing a molecule, such as a polypeptide or nucleic acid molecule, makes use of the conductive channel-containing membrane. A method of DNA sequence makes use of the conductive channel-containing membrane.

Abstract: The present invention is directed towards an artificial RNA nanostructure comprising multiple external strands of RNA, each external strand comprising about 40-50 nucleotides; one internal strand of RNA comprising more than about 50 nucleotides; the internal strands and external strands assembled to form a triangle nanostructure, a square nanostructure, or a polygon nanostructure and a pRNA three-way junction (3WJ) motif at each vertex of the nanostructure. Such nanostructure can be provided in a composition together with an adjuvant for use in inducing the production of high affinity neutralizing antibodies or inhibitory antibodies, inducing the production of cytokines, inducing an immune response in a subject, or a combination thereof.

Abstract: Trifurcate RNA junction domains derived from phi29 pRNA are described that assemble with high affinity and that are stable in vitro and in vivo. Further expansion of trifurcated RNA domains to multiple way junction scaffolds via creative designs enable an array of toolkit to construct nanoparticle architectures with diverse shapes and angles. The scaffolds can be used to form RNA nanoparticles having a wide variety of uses, including promotion of RNA crystallization, creation of RNA aptamer with high affinity to mimic antibody, delivery of therapeutic and/or diagnostic agents such as biologically active RNA-based moieties, including siRNA, ribozymes, aptamers, and others.

Abstract: Compositions and methods are disclosed that exploit the unprecedented modification of double-stranded DNA virus DNA-packaging motor protein connector polypeptides to render them capable of stable incorporation into lipid membranes as a self-assembled homodocamer that forms an aperture through which conductance can occur when an electrical potential is applied across the membrane. The aperture permits use of the modified protein as a biosensor, for dsDNA sequencing, SNP detection and highly sensitive affinity capture and fingerprinting of analytes, and also finds use in electropotential-driven solute translocation, such as for liposomal loading to form therapeutic nanoparticles (e.g., gene delivery) and bioreactors, and for other uses. The aperture can further be used in optical detection of dsDNA or other acceptor labeled analytes in a fluorophore donor labeled single pore channel.

Abstract: Compositions and methods are disclosed that exploit the unprecedented modification of double-stranded DNA virus DNA-packaging motor protein connector polypeptides to render them capable of stable incorporation into lipid membranes as a self-assembled homodocamer that forms an aperture through which conductance can occur when an electrical potential is applied across the membrane. The aperture permits use of the modified protein as a biosensor, for dsDNA sequencing, SNP detection and highly sensitive affinity capture and fingerprinting of analytes, and also finds use in electropotential-driven solute translocation, such as for liposomal loading to form therapeutic nanoparticles (e.g., gene delivery) and bioreactors, and for other uses. The aperture can further be used in optical detection of dsDNA or other acceptor labeled analytes in a fluorophore donor labeled single pore channel.