Abstract: The present disclosure relates to glyconucleic acids, such as glycoRNA and glycoDNA described herein. Provided are glycosylated ribonucleic acid (glycoRNA)-related methods and compositions.

Abstract: A series of carbohydrate-dye conjugates, as well as a method for detection of pathogenic or other organisms (e.g., bacteria) using the same are provided. The carbohydrate-dye conjugate can be enzymatically incorporated into live and active (viable) bacteria of interest for facile detection of said bacteria. The conjugate incorporation is achieved by utilizing one or more of the enzymes that are endogenous to the bacteria of interest, which can incorporate the conjugate via the conjugate's carbohydrate. A detectable signal is produced by the conjugate's dye only upon incorporation into the bacteria of interest, due to the changes in the dye's local environment upon incorporation. The conjugate may be metabolically incorporated into the fatty outer membrane of a bacterial cell wall, which provides a distinctly hydrophobic environment for the conjugate's dye, causing it to produce a detectable signal.

Abstract: Provided are bifunctional molecules that include a first moiety that specifically binds a cell surface molecule or extracellular molecule, and a second moiety that specifically binds a lysosomal targeting molecule. The bifunctional molecules find use, e.g., for targeted degradation of cell surface and extracellular molecules (e.g., proteins) via the endosomal/lysosomal pathway. Also provided are compositions and kits that include the bifunctional molecules, as well as methods of using the bifunctional molecules. Methods of making bifunctional molecules are also provided.

Abstract: The present disclosure relates to glycan-modified nucleic acids, including short interfering RNA molecules. The glycan-modified nucleic acids include an oligosaccharide moiety that is bond to the nucleic acid and that contains a multiple antennary complex type N-glycan. The disclosure also relates to pharmaceutical compositions containing such glycan-modified nucleic acids, and methods for making and using such glycan-modified nucleic acids.

Abstract: Provided are conjugates including a targeting moiety that binds to a cell surface molecule of a target cell and a target cell surface-editing enzyme. Also provided are compositions and kits that include the conjugates, as well as methods of using the conjugates. Methods of making conjugates are also provided.

Abstract: The current invention pertains compositions and methods to generate compositions providing stability to biomolecules, including providing physiologically stable and functional DNA origami-based drug/gene delivery carriers by surface coating with the oligo-ethylene glycol conjugated peptoids of Formulas (I), (II), and (III).

Abstract: Provided are cis-binding Siglec agonists. In certain embodiments, the cis-binding Siglec agonists comprise a scaffold bearing Siglec ligands, and a membrane-tethering domain. Also provided are compositions, e.g., pharmaceutical compositions, comprising any of the cis-binding Siglec agonists of the present disclosure. Methods of agonizing Siglec activity, e.g., in an individual in need thereof, are also provided. Kits comprising the cis-binding Siglec agonists, as well as methods of making the cis-binding Siglec agonists, are also provided.

Abstract: Provided are bifunctional molecules that include a first moiety that specifically binds a cell surface molecule, and a second moiety that specifically binds a lysosomal targeting molecule. In certain embodiments, the first moiety is a knottin peptide comprising an engineered loop that binds to the cell surface molecule. The bifunctional molecules find use, e.g., for targeted degradation of cell surface molecules (e.g., proteins) via the endosomal/lysosomal pathway. Also provided are compositions and kits that include the bifunctional molecules, as well as methods of using the bifunctional molecules. Methods of making bifunctional molecules are also provided.

Abstract: The present disclosure relates to glyconucleic acids, such as glycoRNA and glycoDNA described herein. Provided are glycosylated ribonucleic acid (glycoRNA)-related methods and compositions.

Abstract: Provided are conjugates including a targeting moiety that binds to a cell surface molecule of a target cell and a target cell surface-editing enzyme. Also provided are compositions and kits that include the conjugates, as well as methods of using the conjugates. Methods of making conjugates are also provided.

Abstract: Provided are methods of enhancing immunogenicity of cancers. In certain aspects, the methods include administering an effective amount of a sialic acid modulator to an individual identified as having a cancer comprising dysregulated Myc. According to some aspects, the methods include administering an effective amount of a disialyl-T modulator to an individual identified as having a cancer comprising cell surface expression of disialyl-T. In certain aspects, the methods include administering an effective amount of an agent to an individual identified as having a cancer comprising cell surface expression of a glycoprotein comprising an O-glycosylated mucin-like domain, where the agent modulates the glycoprotein. Also provided are methods of assessing whether a cancer of an individual comprises dysregulated Myc.

Abstract: Provided are conjugates comprising a knottin peptide comprising an engineered loop that binds to a cell surface molecule, and an immunostimulant conjugated to the knottin peptide via a linker. According to some embodiments, the immunostimulant activates a pathogen recognition receptor (PRR). For example, the immunostimulant may be a Toll-Like Receptor (TLR) agonist, e.g., an agonist of TLR 7, TLR 8 and/or TLR 9. Also provided are compositions (e.g., pharmaceutical compositions) that comprise the conjugates of the present disclosure, as well as kits comprising such compositions and methods of using such compositions, e.g., to treat an individual having cancer. Methods of making the conjugates of the present disclosure are also provided.

Abstract: Provided are methods relating to the inhibition of inhibitory immune receptors. Aspects of the present disclosure include methods that include administering to an individual receiving an antibody therapy an inhibitory immune receptor inhibitor. Also provided are compositions and kits that find use, e.g., in practicing the methods of the present disclosure.

Abstract: Methods of treating a subject for a neurodegenerative disorder are provided. Aspects of the methods include administering to a subject in need thereof an effective amount of an agent that reduces the prevalence of lipid droplet accumulating microglia (LAM) to treat the subject for the neurodegenerative disorder. A variety of neurodegenerative disorders may be treated by practice of the methods. Also provided are methods of identifying lipid droplet-associated target genes, including target genes that are positive and negative regulators of lipid droplet formation, as well as methods of treating a neurodegenerative disorder in a subject by administering to the subject an antagonist of a positive regulator of lipid droplet formation and/or an agonist of a negative regulator of lipid droplet formation.

Abstract: The present disclosure provides compositions and methods involving the use of mucin-specific proteases for mucin-specific cleavage, labeling, and/or enrichment of mucin domain glycoproteins. Also provided are methods for the analysis of mucin-domain glycoproteins useful in glycomapping of mucin glycosites and their associated glycoforms. Provided compositions and methods are also useful for selective cleavage, release, and enrichment of mucins from cell and tissue samples, for the study of native mucin biology, and for the detection and analysis of mucins that are aberrantly expressed in various conditions, including cancer.

Abstract: Methods are provided for treatment of cancer cells, in a regimen comprising contacting the cancer cells with an inhibitor on NGly1, optionally in combination with a direct proteasome inhibitor.

Abstract: Pharmaceutical compositions are provided for extending the serum half-life of a therapeutic agent. The composition may include a strained alkyne-labeled therapeutic agent. Also provided is a strained alkyne-carrier protein adduct including a vinyl thioether-linkage to a cysteine residue of the carrier protein. Methods of chemoselectively modifying a carrier protein are provided, that include conjugating a cysteine residue of a carrier protein with a cyclooctyne-labeled cargo agent to produce a vinyl thioether-linked conjugate. Also provided is a method of increasing the in vivo half-life of a bioactive agent including administering a strained alkyne-labeled bioactive agent to a subject.

Abstract: Methods are provided for detecting a glycosylated target protein in a sample. Aspects of the methods include: (a) contacting a sample comprising a probe-labeled glycosylated target protein with: (i) a first conjugate comprising a first nucleic acid tag linked to a first capture agent that specifically binds the target protein; (ii) a second conjugate comprising a second nucleic acid tag linked to a second capture agent that specifically binds the probe; and (iii) a bridging nucleic acid that hybridizes to the first and second nucleic acid tags; under conditions sufficient to specifically bind the first and second capture agents to the probe-labeled target protein and to hybridize the bridging nucleic acid to the first and second nucleic acid tags to produce a nucleic acid complex; and (b) detecting the nucleic acid complex. Also provided are compositions and kits useful in practicing various embodiments of the subject methods.

Abstract: The current invention pertains compositions and methods to generate compositions providing stability to biomolecules, including providing physiologically stable and functional DNA origami-based drug/gene delivery carriers by surface coating with the oligo-ethylene glycol conjugated peptoids of Formulas (I), (II), and (III).

Abstract: Methods for producing isotopically-labelled peptides are provided. Aspects of the method include: contacting a sample including a metabolically tagged protein with a cleavable probe to produce a probe-protein conjugate; separating the probe-protein conjugate from the sample; digesting the probe-protein conjugate to produce a probe-peptide conjugate; and cleaving a cleavable linker to release an isotopically labelled peptide. The method may further include: identifying a predetermined isotopic pattern in a mass spectrum; determining an amino acid sequence of the isotopically labelled peptide; and identifying the site of protein glycosylation based on the determined amino acid sequence. Also provided are cleavable probes for practicing the subject methods, described by the Formula: A-L-(M-Z) where A is an affinity tag, L is a cleavable linker, M is an isotopic label and Z is a chemoselective tag capable of cross-linking a metabolically tagged protein.