Abstract: Compositions and methods are provided for the reversible modification of RNA to enhance RNA in-solution and enzymatic stability by reaction with acylimidazoles, sulfonyltriazoles, or sulfonylimidazoles. 2?-OH acylation protects RNA from hydrolytic and enzymatic degradation. Water-soluble organocatalysts can accelerate the reversal of acylation adducts and functionally restore RNAs, alternatively the acylation is spontaneously reversed in a cellular environment. Chemically tuned 2?-OH acylation can be spontaneously released in cells to restore RNA biological functions including translation. mRNA can be selectively modified at the 2?-OH of poly(A)-tail for enhanced in-cell stability and enhanced total protein output.

Abstract: Compositions and methods are provided for a biochemical method for detecting virus RNA sequences, either after isolation or directly in patient samples, by detecting ATP released from an ATP-releasing nucleotide (ARN) during synthesis. In some embodiments the virus is a coronavirus, e.g. SARS-CoV2.

Abstract: Reagents and methods to cloak and uncloak RNA polymers and applications thereof are provided. Photocloaking molecules are used to label RNA polymers. Radiant energy is used to remove photoreleaseable protecting adducts and revert a RNA polymer to its native form.

Abstract: Noncovalent small-molecule inhibitors of the enzyme OGG1, methods of their manufacture, and applications for their administration are provided. Small molecule inhibitors were shown to be selective for inhibiting OGG1 over multiple repair enzymes, including other base excision repair enzymes, and it displayed no toxicity in two human cell lines. The inhibitors provide a tool for the study of the role of OGG1 in multiple disease-related pathways, and a therapeutic target for the treatment thereof.

Abstract: Probes, methods and kits for detecting and measuring abasic (AP) sites in a nucleic acid are provided. Aspects of the methods include determining glycosylase enzyme activity. Further provided herein are methods of quantifying AP sites in genomic DNA, and quantifying the amount of DNA damage. The subject probes include a fluorophore linked to an alpha nucleophile that reacts with the AP site of the nucleic acid to produce a highly fluorescent conjugate.

Abstract: Noncovalent small-molecule inhibitors of the enzyme OGG1, methods of their manufacture, and applications for their administration are provided. Small molecule inhibitors were shown to be selective for inhibiting OGG1 over multiple repair enzymes, including other base excision repair enzymes, and it displayed no toxicity in two human cell lines. The inhibitors provide a tool for the study of the role of OGG1 in multiple disease-related pathways, and a therapeutic target for the treatment thereof.

Abstract: Reagents and methods to cloak and uncloak RNA polymers and applications thereof are provided. Photocloaking molecules are used to label RNA polymers. Radiant energy is used to remove photoreleaseable protecting adducts and revert a RNA polymer to its native form.

Abstract: Compositions and methods are provided for detecting activity of nucleotide pool repair enzymes. In the methods of the invention, a sample suspected of having nucleotide pool repair enzyme activity is combined with a detection compound provided herein, which detection compound comprises (i) a substrate for the enzyme of interest, (ii) a polyphosphate linker; and (iii) a detection moiety that is active when released by the enzyme of interest cleaving the linker.

Abstract: The presence of a target polynucleotide sequence of interest, including targets comprising genetic variations or a single nucleotide polymorphism, is detected by a DNA polymerization reaction, where the reaction mixture includes mixtures of nucleotides including at least one chimeric nucleoside tetraphosphate dimer ATP-linked nucleotide (ARN), in which ATP is the leaving group. DNA synthesis with ARNs is shown to be sequence specific, based on priming with a primer or template complementary to a target sequence. The released ATP is assayed in a qualitative or quantitative analysis, where one equivalent of ATP is released for every deoxynucleotide incorporated from an ARN.

Abstract: Telomere-encoding nucleic acid nanocircles, methods for their preparation, and methods for their use are disclosed. The nanocircles can be constructed containing multiple repeats of the complement of telomere repeat sequences. The telomere-encoding nanocircles are useful for extending telomeres both in vitro and in vivo, for treating macular degeneration, the effects of skin aging, liver degeneration, and cancer. The nanocircles are further useful for treating cell cultures to produce long-lived non-cancerous cell populations. This use has wide applicability in scientific research, tissue engineering, and transplantation.

Abstract: The present invention provides methods for synthesis and therapeutic use of DNA and RNA oligonucleotides and analogs. RNA oligonucleotides are synthesized using a small, circular DNA template which lacks an RNA polymerase promoter sequence. The RNA synthesis is performed by combining a circular single-stranded oligonucleotide template with an effective RNA polymerase and at least two types of ribonucleotide triphosphate to form an RNA oligonucleotide multimer comprising multiple copies of the desired RNA oligonucleotide sequence. Preferably, the RNA oligonucleotide multimer is cleaved to produce RNA oligonucleotides having well-defined ends. Preferred RNA oligonucleotide multimers contain ribozymes capable of both cis (autolytic) and trans cleavage.

Abstract: Telomere-encoding nucleic acid nanocircles, methods for their preparation, and methods for their use are disclosed. The nanocircles can be constructed containing multiple repeats of the complement of telomere repeat sequences. The telomere-encoding nanocircles are useful for extending telomeres both in vitro and in vivo, for treating macular degeneration, the effects of skin aging, liver degeneration, and cancer. The nanocircles are further useful for treating cell cultures to produce long-lived non-cancerous cell populations. This use has wide applicability in scientific research, tissue engineering, and transplantation.

Abstract: Novel compounds having a fluorescence quencher as a leaving group are disclosed. Nucleic acids and other molecules containing a fluorophore and a fluorescence quencher are disclosed as an embodiment of this invention. The use of the oligonucleotides in enzyme-free oligonucleotide ligation reactions results in an increase in fluorescence when the oligonucleotide also contains a nearby fluorophore. The ligation reactions can be performed in solution, on surfaces, or in cells.

Abstract: Telomere-encoding nucleic acid nanocircles, methods for their preparation, and methods for their use are disclosed. The nanocircles can be constructed containing multiple repeats of the complement of telomere repeat sequences. The telomere-encoding nanocircles are useful for extending telomeres both in vitro and in vivo, for treating macular degeneration, the effects of skin aging, liver degeneration, and cancer. The nanocircles are further useful for treating cell cultures to produce long-lived non-cancerous cell populations. This use has wide applicability in scientific research, tissue engineering, and transplantation.

Abstract: The present invention provides methods for synthesis and therapeutic use of DNA and RNA oligonucleotides and analogs. RNA oligonucleotides are synthesized using a small, circular DNA template which lacks an RNA polymerase promoter sequence. The RNA synthesis is performed by combining a circular single-stranded oligonucleotide template with an effective RNA polymerase and at least two types of ribonucleotide triphosphate to form an RNA oligonucleotide multimer comprising multiple copies of the desired RNA oligonucleotide sequence. Preferably, the RNA oligonucleotide multimer is cleaved to produce RNA oligonucleotides having well-defined ends. Preferred RNA oligonucleotide multimers contain ribozymes capable of both cis (autolytic) and trans cleavage.

Abstract: Fluorescent glycosides containing aromatic hydrocarbon groups are useful in labelling and detection methods for a wide array of chemical and biological molecules. Assembly of multiple analogs to form “polyfluors” affords fluorescence properties that are different from the properties of the component analogs. This allows for the design and use of combinatorial libraries of molecules displaying widely varying fluorescence colors.

Abstract: The present invention provides methods for synthesis and therapeutic use of DNA and RNA oligonucleotides and analogs. RNA oligonucleotides are synthesized using a small, circular DNA template which lacks an RNA polymerase promoter sequence. The RNA synthesis is performed by combining a circular single-stranded oligonucleotide template with an effective RNA polymerase and at least two types of ribonucleotide triphosphate to form an RNA oligonucleotide multimer comprising multiple copies of the desired RNA oligonucleotide sequence. Preferably, the RNA oligonucleotide multimer is cleaved to produce RNA oligonucleotides having well-defined ends. Preferred RNA oligonucleotide multimers contain ribozymes capable of both cis (autolytic) and trans cleavage.

Abstract: The invention is directed to novel compositions and methods for nonenzymatic ligation of oligonucleotides. In one aspect of the invention, the nonenzymatic ligation is selenium-mediated or tellurium mediated ligation. In another aspect, the invention provides for the use of fluorescence resonance energy transfer (FRET) to detect the nonenzymatic ligation.

Abstract: Novel compounds having a fluorescence quencher as a leaving group are disclosed. Nucleic acids and other molecules containing a fluorophore and a fluorescence quencher are disclosed as an embodiment of this invention. The use of the oligonucleotides in enzyme-free oligonucleotide ligation reactions results in an increase in fluorescence when the oligonucleotide also contains a nearby fluorophore. The ligation reactions can be performed in solution, on surfaces, or in cells.

Abstract: Fluorescent glycosides containing aromatic hydrocarbon groups are useful in labelling and detection methods for a wide array of chemical and biological molecules. Assembly of multiple analogs to form “polyfluors” affords fluorescence properties that are different from the properties of the component analogs. This allows for the design and use of combinatorial libraries of molecules displaying widely varying fluorescence colors.