Disclosed herein are compositions and pharmaceutical formulations that comprise a binding moiety conjugated to a polynucleic acid molecule and a polymer. Also described herein include methods for treating a cancer which utilize a composition or a pharmaceutical formulation comprising a binding moiety conjugated to a polynucleic acid molecule and a polymer.

The present invention serves as a platform technology to deliver RNA therapeutics into cells. It provides a system for delivery of RNA molecules for biomedical purposes. The modular protein-based system described in this invention allows for customization of protein modules to achieve specificity in cell-targeting, thus having the ability to be optimized for treating different diseases. Examples of types of diseases that could adopt this technology for treatment include cancer, neurodegenerative diseases and viral infection.

This disclosure provides compositions and methods for the targeted and localized in vivo delivery of oligonucleotides. Compositions containing targeted oligonucleotide-HES conjugates are provided as are methods of making and using the conjugates in therapeutic, diagnostic, and other applications. The oligonucleotide-HES complexes contained in the targeted oligonucleotide-HES conjugates can cross membranes in a receptor-independent manner and can deliver oligonucleotides to complementary sequences in the cytosol of live cells in vivo. The targeted oligonucleotide-HES conjugates have uses that include the targeted and/or localized delivery of antisense oligonucleotides, siRNAs, shRNAs, Dicer substrates, miRNAs, anti-miRNA, and other nucleic acid sequence in a living organism.

The invention provides compositions and methods for treatment of proliferative vitreoretinopathy.

Described herein are methods, compositions, and systems for gene editing using polynucleotide modifying enzymes that do not require the use of chemical transfection agents for entry into cells.

The present disclosure relates to an isolated compound including a phosphorothioated oligodeoxynucleotide (ODN) sequence conjugated to a short-activating RNA (saRNA) or an antisense oligonucleotide sequence (ASO), compositions of such a compound, and method of treatment of cancer and autoimmune diseases (with or without stimulating immune response), method of immune stimulation, method of activating CEBPA, and method of reducing activity of STAT transcription factor, by one of the disclosed compounds or compositions.

This invention relates to compounds, compositions, and methods useful for reducing KRAS target RNA and protein levels via use of Dicer substrate siRNA (DsiRNA) agents possessing asymmetric end structures.

This invention generally relates to a composition and its method of use for inducing adult stem cell (ASC) expansion and/or derivation in vitro, using miR-302-like pre-miRNAs, shRNAs and/or siRNAs, all of which contain a shared sequence of 5′-UAAGUGCUUC CAUGUUU-3′ (SEQ ID NO: 7) in the 5′-end, and further in conjunction with the use of some wound-healing-related defined factors, including but not limited to basic fibroblast growth factor (bFGF)/fibroblast growth factor 2 (FGF-2), leukemia inhibitory factor (LIF), insulin-like growth factor (IGF), Epidermal growth factor (EGF), platelet-derived growth factor (PDGF), vascular endothelial growth factor (VEGF), transforming growth factor (TGF), tumor necrosis factor (TNF), stem cell factor (SCF), homeobox proteins (HOX), Notch, GSK, Wnt/beta-Catenin signals, interleukins, and/or bone morphogenetic proteins (BMPs). The principle of the present invention is related to a novel mechanism of inducible symmetric ASC division recently found in a skin wound healing model in vivo. The resulting amplified ASCs are useful for treating a variety of human aging- and cell dysfunction-associated disorders, including but not limited to Alzheimer's disease, Parkinson's disease, motor neuron disease, stroke, diabetes, osteoporosis, myocardial infraction, hemophilia, anemia, AIDS, leukemia, lymphoma and many kinds of cancers as well as aging.

The present invention relates to a method for preventing or treating a cancer disease by targeting the epigenetic factor Chromodomain on Y-like 2 (CDYL2). The inventors found that CDYL2 is commonly over-expressed in cancer and high CDYL2 levels correlate with poor prognosis in a number of cancer types even in drug resistant cancer. CDYL2 upregulation in a breast cancer cell line induced migration, invasion, stem-like phenotypes, as well as an epithelial-to-mesenchymal transition (EMT). Due to the importance of EMT and stemness in therapeutic resistance and relapse in cancer, the inventors propose that CDYL2 inhibition will also be beneficial to the treatment of such cancers. Furthermore RNAi inhibition of CDYL2 diminished these same EMT-associated processes in the mesenchymal-like breast cancer cell line. Finally ablating the expression of CDYL2 with RNAi 1) stimulates the expression of genes associated with an anti-tumor immune response (such as gene involved in interferon response) and 2) inhibits lung tumorigenesis in a preclinical model (mouse injected with the triple negative MDA-MB-231 cell line). These results show that CDYL2 as a strong candidate proto-oncogene and therapeutic target in cancer and also contributes to the anti-tumoral immune response escape.

Compositions and methods are provided for silencing the Sulf2 and/or GPC3 genes in vivo. Potent siRNA sequences are provided that silence regions of the Sulf2 and GPC3 genes that are identical in human, mice and non-human primates. Combinations of siRNAs also are provided that result in additivity or synergy with silencing of Sulf2 and/or GPC3. Silencing SULF2+TGFβ1 showed a dramatic effect against cancer growth in vitro and in vivo.