The present technology relates to compositions and methods for modulating expression of genes which include a target oligonucleotide sequence, such as repeats of a particular oligonucleotide sequence containing 3 to 10 nucleotides. In particular aspects, the present technology relates to agents having a formula A-L-B, wherein -L- is a linker; A- is a Brd4 binding moiety; and —B is a nucleic acid binding moiety, such as a polyamide or complementary oligonucleotide, that specifically binds to the target oligonucleotide sequence.

Provided herein are dendrimers comprising: a core unit, five generations of building units which are lysine residues or analogues thereof, first terminal groups comprising a residue of a camptothecin active covalently attached to a diglycolyl linker group, and second terminal groups comprising a PEG group. Also provided herein are pharmaceutical compositions comprising the dendrimer, and methods and uses of the dendrimers in therapy of disorders such as cancers. Processes for making the dendrimers and intermediates are also provided.

The current invention relates to an effector moiety capable of inducing an intracellular effect when present inside a mammalian cell, the effector moiety comprising a payload conjugated with at least one saponin. The invention also relates to an antibody-drug conjugate comprising the effector moiety according to the invention, or a ligand-drug conjugate comprising the effector moiety of the invention, the effector moiety comprising covalently coupled saponin. The invention also relates to a therapeutic combination comprising: (a) the effector moiety of the invention, comprising at least one saponin, and optionally a pharmaceutically acceptable excipient; and (b) an antibody-drug conjugate or a ligand-drug conjugate, and optionally a pharmaceutically acceptable excipient. Further, the invention relates to a pharmaceutical composition comprising the effector moiety of the invention or the antibody-drug conjugate of the invention or the ligand-drug conjugate of the invention, comprising at least one saponin covalently linked to the effector molecule, and optionally a pharmaceutically acceptable excipient. The invention also relates to the effector moiety of the invention or the antibody-drug conjugate of the invention or the therapeutic combination of the invention or the ligand-drug conjugate of the invention or the pharmaceutical composition of the invention, for use as a medicament. Finally, the invention also relates to the effector moiety of the invention or the antibody-drug conjugate of the invention or the therapeutic combination of the invention or the ligand-drug conjugate of the invention or the pharmaceutical composition of the invention, for use in the treatment or prevention of a cancer or an autoimmune disease.

A conjugated cationic dendrimer comprising end groups conjugated to charge-shielding groups, wherein some charge-shielding groups are chemically linked to active pharmaceutical ingredients.

The present disclosure provides polymer conjugates comprising a polymer and an agent, the agent linked to the polymer via a linking group containing a hydrolyzable moiety.

A method for treating or preventing one or more symptoms of severe inflammation in the lung of a subject in need thereof includes administering to the subject a composition comprising dendrimers complexed, covalently conjugated, or intra-molecularly dispersed or encapsulated with one or more therapeutic or prophylactic agents, in an amount effective to treat, alleviate or prevent one or more symptoms of severe inflammation. The compositions and methods are useful for treating disorders characterized by cytokine storm, for example, for treating or preventing acute lung injury (ALI) and/or acute respiratory distress syndrome (ARDS) results in from ventilator use or infection such as with COVID-19, sepsis, and systemic bacterial infections in a subject in need thereof have been established. Preferably, the dendrimers are generation 4, 5, 6, 7, or 8 poly(amidoamine) (PAMAM) dendrimers, and the therapeutic agents are one or more anti-inflammatory and/or anti-oxidant agents such as N-acetyl cysteine.

An antiviral agent is provided, having a phosphorodiamidate morpholino oligomer with an antisense sequence to a portion of a genome of a strain of Zika virus (ZIKV). The antiviral agent finds many uses, such as in a pharmaceutical composition, a method of treating ZIKV-mediated disease, a method of preventing ZIKV-mediated disease, a method of reducing or preventing the replication of ZIKV in a host cell, a method of controlling the spread of ZIKV in donated tissue, a treated tissue sample, and in the manufacture of a medicament for the treatment or prevention or ZIKV-mediated disease.

The present disclosure belongs to the field of pharmaceutical preparations and relates to the design of a series of lipophilic derivatives by using wild-type penetrating peptide penetratin. These penetratin derivatives have a strong ability to penetrate the ocular tissues and do not cause ocular tissue toxicity. As ocular absorption enhancers, non-invasive routes could be used to achieve intraocular drug delivery and increase the ocular bioavailability of drugs. These penetratin derivatives and the ophthalmic drug delivery system constructed by them are used for eye drop administration, which could replace the intraocular injection with poor patients compliance, which greatly enhances the convenience and safety of the treatment of intraocular and fundus diseases.

Conjugates of synthetic nanocarriers, complexed with syngeneic (self) proteins adducted with haptens or other poorly immunogenic antigens (antigens of low immunogenicity), elicit selective humoral responses or antibodies against the hapten or antigen and not to self-protein. Compositions include these conjugates, which can be used as vaccines. Methods of making and using them are described herein. In a typical embodiment, a conjugate including a hapten or antigen of low immunogenicity associated with a particular disease (e.g., infection, cancer) can be used as a vaccine by eliciting antibodies that specifically neutralize the hapten or antigen. These hapten (and other poorly immunogenic antigen)-carrying nanocarriers selectively target antigen presenting cells resulting in a strong anti-hapten humoral response, and thus find use in vaccines for cancer (e.g., cancers of lung, cervix, breast, brain, liver pancreas, ovaries, skin, etc.), infectious diseases and inflammatory-mediated diseases, as well as for autoimmune disorders.

A nanoparticle delivery system designed for sustained delivery of microRNA-150 (miR-150) to FLT3-overexpressing acute myeloid leukemia (AML) cells, the delivery system comprising poly(amidoamine) (PAMAM) dendrimers complexed with miR-150, wherein at least one dendrimer is surface-functionalized with a ligand specific for FLT3 receptor, and methods for treating AML characterized by FLT3-overexpression are provided.