Disclosed are molecules for treating non-del(5q) MDS that mimic allelic deficiency in del5q MDS to sensitize the malignant clones of patient without del(5q). The disclosed molecule contains an inhibitor of Cdc25C, an inhibitor of PP2Ac, or a combination thereof, and a toll like receptor-9 (TLR9) targeting ligand. The molecule can also contain lenalidomide, or an analogue or derivative thereof. Also disclosed is a composition comprising the disclosed molecule in a pharmaceutically acceptable carrier. Also disclosed is a method for treating non-del(5q) meylodysplastic syndrome (MDS) in a subject by administering to the subject a therapeutically effective amount of the disclosed pharmaceutical composition.

Provided herein are oligomeric compounds with conjugate groups. In certain embodiments, the oligomeric compounds are conjugated to N-Acetylgalactosamine.

This disclosure relates to modified viruses, e.g., oncolytic vaccinia viruses, which have been modified to contain an exogenous nucleic acid that expresses a protein that modulates STAT3 activity. It is based, at least in part, on the discovery that vaccinia viruses modified to contain nucleic acid encoding PIAS3 and that express PIAS3 or a fragment thereof can inhibit STAT3 activity and enhance the anti-cancer activity of the vaccinia virus. Accordingly, this disclosure provides for oncolytic vaccinia viruses and methods of using them in the treatment of cancers.

The present invention provides a modified induced pluripotent stem cell iPSC or haemogenic lineage cell comprising at least one heterologous nucleic acid sequence encoding a heterologous T-cell receptor (TCR) integrated in the cell genome and uses thereof.

Provided are Shp2- and Spleen tyrosine kinase (Syk)-integrated sensing and actuating protein (iSNAP) (Shp2- and Syk-iSNAP) chimeric proteins comprising: a bi-phosphorylatable peptide, optionally a bisphosphoryl tyrosine-based activation (BTAM) motif; a Fluorescent Protein (FP) Frster Resonance Energy Transfer (FRET) (or FP FRET) pair or pair of motifs; a truncated Shp2 domain comprising an N-Src Homology 2(N-SH2) domain and a C-Src Homology 2(C-SH2) domain; and, a phosphatase (PTP) domain or a kinase domain. Provided are engineered cells and methods for cancer cell or tumor eradication, or for the treatment or amelioration of a cancer, tumor or dysfunctional cell, or for promoting an anti-cancer, anti-tumor or anti-dysfunctional cell inflammatory response, including enhancing macrophage-, monocyte-, microglia-, osteoclast-, Kupffer cell- or dendritic cell-mediated antibody- or monoclonal antibody (mAb)-guided cancer or dysfunctional cell or tumor eradication, amelioration, or treatment.

Provided herein are methods to identify agents or compounds that specifically modulate the oligomerization and/or functional activities of receptor protein tyrosine phosphatase sigma (RPTP) in an abnormal fibroblast cell and therapies based therefrom.

Provided herein are compositions, systems, kits, and methods for treating nervous system injuries caused by trauma or neurodegeneration or aging in a subject by administering a CSPG or SOCS3 reduction peptide (CRP and SRP respectively), or a nucleic acid sequence encoding the CRP or SRP, wherein both the CRP and SRP comprise a cell membrane penetrating domain, and a lysosome targeting domain, and the CRP further comprises a chondroitin sulfate proteoglycan (CSPG) binding domain, and the SRP further comprises a suppressor of cytokine signaling-3 (SOCS3) binding domain.

A method of treating cancer in a subject includes administering to the subject a therapeutically effective amount of an agent that specifically binds to or complexes with a proteolytically cleaved extracellular fragment of an immunoglobulin (Ig) superfamily cell adhesion molecule (CAM) or its receptor that is expressed by a cancer cell or another cell in the cancer cell microenvironment. The agent inhibits the cell adhesion function of the cleaved extracellular fragment or its receptor.

The present invention is directed to a method for extracting recombinant proteins from bacteria by Ph shock.

Nanoparticulate pharmaceutical formulations and methods for co-delivery of two or more species of nucleic acids for simultaneous suppression and expression of target genes in a cell, are provided. The nanoparticles encapsulate two or more nucleic acid species. The first nucleic acid suppresses expression of a gene or product thereof, e.g., inhibitory nucleic acid, such as antisense, siRNA, miRNA, Dicer siRNA, piRNA, etc. The second nucleic acid increases expression of, or encodes, an endogenous or exogenous protein or polypeptide, e.g., an mRNA. The first and second nucleic acid species simultaneously target or affect the same or different cellular processes within a cell including communication, senescence, DNA repair, gene expression, metabolism, necrosis, and apoptosis.