Provided are a double-stranded siRNA analogue embedded with a ribavirin derivative, a conjugate containing same, and a salt and the use thereof. The provided double-stranded siRNA analogue, the conjugate containing same and the salt thereof can effectively inhibit multiple viral indicators such as hepatitis B virus DNA, pgRNA, S antigen, and E antigen, which provide an effective and feasible method for treating hepatitis B.

The present invention relates to compositions comprising a delivery vehicle conjugated to a targeting domain, wherein the delivery vehicle comprises at least one agent, and wherein the targeting domain specifically binds to an CD4.sup.+ T cell antigen. The invention also relates to methods of treating or preventing diseases and disorders, including cancers, infectious diseases, and immunological disorders, using the described compositions.

The present disclosure is directed to bifunctional small molecules which contain a circulating protein binding moiety (CPBM) linked through a linker group to a cellular receptor binding moiety (CRBM) which is a membrane receptor of degrading cell such as a hepatocyte or other degrading cell. In certain embodiments, the (CRBM) is a moiety which binds to asialoglycoprotein receptor (an asialoglycoprotein receptor binding moiety, or ASGPRBM) of a hepatocyte. In additional embodiments, the (CRBM) is a moiety which binds to a receptor of other cells which can degrade proteins, such as a LRP1, LDLR, FcγRI, FcRN, Transferrin or Macrophage Scavenger receptor.

The present invention provides a nanogel nasal vaccine that induces cell-mediated immunity. The present invention relates to a vaccine preparation comprising a complex of a nanogel, a vaccine antigen, and an adjuvant, wherein the vaccine preparation can efficiently induce the cell-mediated immunity, and can also induce a systemic and mucosal immune response.

The invention concerns fusion proteins, wherein two endoglycosidases are fused, possibly via a linker. The fusion enzymes according to the invention have structure (1): EndoX-(L).sub.p-EndoY (1), wherein EndoX is an endoglycosidase, EndoY is an endoglycosidase distinct from EndoX, L is a linker and p is 0 or 1. Such fusion enzymes capable of trimming glycoproteins comprising at least two distinct glycoforms in a single step. The invention further concerns the use of the fusion enzyme according to the invention for trimming glycoproteins. In another aspect, the invention relates to the process of production of the fusion enzyme. In a further aspect, the inventions concerns a process for trimming glycoproteins, comprising trimming the glycoprotein with a fusion enzyme according to the invention, to obtain a trimmed glycoprotein.

The present invention provides a half-life extension drug and a library thereof, and a preparation method and application thereof. Specifically, the present invention provides a drug library, comprising: (a) a drug unit; and (b) n half-life extension units, wherein the drug unit comprises a drug element portion and a first nucleic acid element portion connected to the drug element portion, and each half-life extension unit comprises a half-life extension element portion and a second nucleic acid element portion connected to the half-life extension element portion. Moreover, one first nucleic acid element portion of the drug unit and the second nucleic acid element portion of the at least one half-life extension unit may form a “drug unit-half-life extension unit” complex by forming a complementary base pairing structure, and n is a positive integer greater than or equal to 1.

The present disclosure relates to novel RNAi agents designed to decrease the expression of ANGPTL8 in the liver, where the RNAi agents comprise delivery moieties conjugated to oligonucleotides optionally via a linker. The RNAi agents are useful in the treatment of diseases involving the regulation of ANGPTL8 expression.

The design, synthesis, and biological evaluation of a new family of highly effective conjugate compounds, including dendrimeric moieties and branched structures, are described. Pharmaceutical compositions including the subject dendrimeric conjugates and methods of using the same are also provided. Methods of using the subject dendrimeric conjugates include delivering a cargo moiety conjugated to the dendrimeric moieties and branched structures to a cell under suitable conditions. In certain embodiments, the cell is a bacterial cell population, and the subject compounds reduce the bacterial cell population. In certain embodiments of the methods, the subject compound is capable of eradicating one or more of Gram-positive bacteria, mycobacteria, and Gram-negative bacteria. In certain embodiments of the methods, the subject compound is capable of eradicating bacterial biofilms. Methods of using the subject dendrimeric conjugates include treating a subject for a disease or condition. In certain embodiments, the disease or conditions an infectious disease.

A method for inhibiting expression of an mRNA having an expanded trinucleotide repeat region is provided comprising administering an oligomer comprising a sense strand and an antisense strand wherein: a) the antisense strand comprises a sequence of Formula (I): rGrCrUrGrCrUrGrCX.sup.1X.sup.2rCrUrGrCrUrGrCrUrG (I), wherein X.sup.1 and X.sup.2 are each independently selected from rA, rU, rG, rC, UNA-A, UNA-U, UNA-G, and UNA-C and wherein at least one of X.sup.1 and X.sup.2 is a UNA monomer; b) the oligomer comprises a UNA monomer at the first position at the 5′-end of the sense strand; and the sense strand and the antisense strand each independently include 19-29 monomers. The oligomer can be formulated in a lipid delivery vehicle, and can inhibit expression of Atrophin-1, Huntingtin, Ataxin-1, Ataxin-2, Ataxin-3, Ataxin-7, Alpha1A-voltage-dependent calcium channel subunit, TATA-box binding protein (TBP), Androgen Receptor, PP2A-PR55beta, FMR-1 Protein (FMRP), FMR-2 protein, Frataxin, Dystrophy Protein Kinase (DMPK), or Ataxin-8.

This disclosure provides compositions and methods for delivering a viral composition to cells, e.g., for cell surface receptor-mediated uptake, and enhanced viral transduction. Viral transduction can be achieved via a bifunctional bridging composition that includes a moiety that binds to a cell surface receptor ligand and a linked bridging moiety that binds to a viral composition. Also provided are modified viral compositions comprising a bridging composition specifically bound via its bridging moiety to the viral composition. Modified viral compositions and methods for reducing levels or titers of neutralizing antibodies in a subject in need of viral therapy, e.g., gene therapy, are provided. In some embodiments, the modified viral composition includes empty viral particles that bind and internalize neutralizing autoantibodies. Modified viral compositions including empty viral particles can be administered prior to viral therapy. Also provided are pharmaceutical compositions and kits including a bifunctional bridging composition and/or modified viral compositions.