32 results about "E2F" patented technology

Viral vectors and methods of making such vectors are described that preferentially kill neoplastic but not normal cells, the preferred vector being an adenovirus that has the endogenous promoters in the E1A and / or E4 regions substituted with a tumor specific promoter which is preferably E2F responsive.

Viral vectors and methods of making such vectors are described that preferentially kill neoplastic but not normal cells, the preferred vector being an adenovirus that has the endogenous promoters in the E1A and / or E4 regions substituted with a tumor specific promoter which is preferably E2F responsive.

The present invention relates to a gene expression regulating sequence consisting of a combination of HRE, E2F and TERT, and to a gene delivery system having significantly improved selective tumor cell cytotoxicity using same, and more particularly, to a recombinant adenovirus. In addition, the present invention relates to a pharmaceutical antitumor composition comprising the recombinant adenovirus. The replication of the recombinant adenovirus of the present invention is tumor-specifically regulated by the novel gene expression regulating sequence of the present invention, thus enabling the recombinant adenovirus of the present invention to exhibit improved selective tumor cell cytotoxicity or apoptotic potential, and exhibit remarkably improved antitumor effects particularly in hypoxic conditions. In addition, the specific expression of the recombinant adenovirus in tumor cells may increase in vivo stability, and thus may induce greatly improved antitumor effects.

Viral vectors and methods of making such vectors are described that preferentially kill neoplastic but not normal cells, the preferred vector being an adenovirus that has the endogenous promoters in the E1A and / or E4 regions substituted with a tumor specific promoter which is preferably E2F responsive.

The instant invention provides amino acid sequences competing with E2F for DNA binding. Methods of using said amino acid sequences for treatment of hormone-refractory prostate cancer are also provided.

Selectively replicating oncolytic adenoviral vectors comprising an adenoviral packaging signal, a termination signal sequence, an E2F responsive promoter operably linked to an adenoviral coding region, a heterologous coding sequence encoding GM-CSF and a right ITR are provided. The oncolytic adenoviral vectors are useful for expressing GM-CSF in transduced cells and in methods for selectively killing neoplastic cells.

The present invention relates to transgenic animals, as well as compositions and methods relating to the identification of prolifering cells. Specifically, the present invention provides transgenic mice having a nucleic acid comprising an E2F responsive promoter operably linked to a nucleic acid encoding a bioluminescent protein. Such transgenic mice are useful as models for disease and for identifying agents that modulate gene expression and are potential treatments for various disease states and disease conditions such as cancer.

A method for the treatment of a proliferative disease comprising providing a E2F-1 protein which is arginine-methylation defective or administering a substance which reduces the expression and / or activity of PRMT5. The invention also provides antibodies, screening methods and kits.

The invention provides a novel recombinant oncolytic adenovirus expressing human interleukin 15. Specifically, the gene promoter of a type 5 adenovirus E1 region is replaced with a transcription factor E2F-1 gene, and an hIL-15 gene is inserted to an E3 region to construct the recombinant oncolytic adenovirus. According to the invention, E2F-1 is used as the promoter to realize replication of virus specificity in tumor cells, and at the same time, loading of human IL-15 gene in a virogene E3 region can further enhance the anti-tumor effect of the virus. As the pRb / E2F pathway defects exist extensively in solid tumors, through the tumor resolving effect of the virus, a variety of tumor antigens from the individual itself can be acquired, and are not limited by antigen subcellular localization, thus being conducive to producing anti-tumor immune response with self tumor specificity, and having individualized and general treatment significance. In addition, the virus replication process drives the IL-15 gene expression, high concentration IL-15 can be obtained from a part of the virus-infected tumor cell, thereby being in favor of stimulating the activity of immune cells, activating the general immune response and strengthening the antitumor effect.

The purification of native RB (retinoblastoma) as a complex, including P107, P130, and a 600 kDa subunit, termed MTAF600 (microtubule associated factor 600) is described. MTAF600 binds to RB regardless of the phosphorylation status of RB, and binds to RB without disrupting the interaction between RB and E2F. It is further shown that E2F and DP proteins co-purified with MTAF600 and RB, such that hypophosphorylated RB may gain access to E2F as a complex with MTAF600. In addition, MTAF600 binds to microtubules and plays a role in active repression of E2F-responsive genes, cell cycle arrest, and genomic stability. The sequence of MTAF600 is described herein, along with its binding properties to proteins such as RB and microtubules, and its sequence homology. Further, methods and reagents for assaying the presence of MTAF600 or mutants thereof, pharmaceutical formulations, and methods for treating disease are also described.

The invention relates to an application of an OsSBR1 gene and an RNA interference fragment thereof for controlling rice sheath blight resistance. The OsSBR1 gene has disease resistance to rice sheath blight fungus under the condition of inhibiting expression in rice. The invention utilizes RNAi transgenic technology to obtain the OsSBR1 sheath blight resistant rice gene, which can be applied to the creation of sheath blight resistant transgenic rice and the cultivation of sheath blight resistant rice varieties; and the untransformed recipient rice variety "Taijing 394" In comparison, the sheath blight resistance of OsSBR1-RNAi transgenic plants is significantly improved; the present invention also confirms that the expression of OsSBR1 gene is suppressed, and rice disease resistance-related genes OsPR1, OsPR1b, PBZ1, E2F-related gene, PDR and PR3 are overexpressed, The resistance of the transgenic plants to sheath blight is significantly improved, which is a new discovery about the molecular mechanism of rice sheath blight resistance.

A purpose of the present invention is to develop an immuno-viral therapy vector that has an optimal therapeutic effect while ensuring a high degree of safety, on the basis of the novel concept of finding the optimal expression level of a therapeutic gene to bring about the maximum therapeutic effect with no side effects. The present invention provides an oncolytic virus or similar that is characterized by having an immunogenic gene that is functionally linked downstream of an E2F promoter or a promoter demonstrating the same activity as an E2F promoter, wherein a promoter of nucleic acids coding for at least one factor that is essential for virus replication or assembly is substituted with a promoter of a factor for which expression is organ-specifically enhanced, or a promoter of a factorfor which expression is cancer cell-specifically enhanced.

A method for the treatment of a proliferative disease comprising providing a E2F-1 protein which is arginine-methylation defective or administering a substance which reduces the expression and / or activity of PRMT5. The invention also provides antibodies, screening methods and kits.

Selectively replicating oncolytic adenoviral vectors comprising an adenoviral packaging signal a termination signal sequence, an E2F responsive promoter operably linked to an adenoviral coding region, a heterologous coding sequence encoding GM-CSF and a right ITR are provided. The oncolytic adenoviral vectors are useful for expressing GM-CSF in transduced cells and in methods for selectively killing neoplastic cells.

The purification of native RB (retinoblastoma) as a complex, including P107, P130, and a 600 kDa subunit, termed MTAF600 (microtubule associated factor 600) is described. MTAF600 binds to RB regardless of the phosphorylation status of RB, and binds to RB without disrupting the interaction between RB and E2F. It is further shown that E2F and DP proteins co-purified with MTAF600 and RB, such that hypophosphorylated RB may gain access to E2F as a complex with MTAF600. In addition, MTAF600 binds to microtubules and plays a role in active repression of E2F-responsive genes, cell cycle arrest, and genomic stability. The sequence of MTAF600 is described herein, along with its binding properties to proteins such as RB and microtubules, and its sequence homology. Further, methods and reagents for assaying the presence of MTAF600 or mutants thereof, pharmaceutical formulations, and methods for treating disease are also described.

The invention discloses a natural small molecular compound and its application in the preparation of antitumor drugs. The small molecular compound is isolated from the fruiting body of Albatrellus confluens, and has a new type of C-skeleton composed of a pyrane-type sesquiterpene-like structure as a side chain connected with resorcinol, named Neoalbaconol. A series of studies have found that Neoalbaconol inhibits tumor cell proliferation and induces tumor cell apoptosis by inhibiting NF-κB, E2F-1 and PI3K / AKT / TSC2 / mTOR signaling pathways. It has significant broad-spectrum anti-tumor activity and can be used to prepare antineoplastic drugs.

The instant invention provides amino acid sequences competing with E2F for DNA binding. Methods of using said amino acid sequences for treatment of hormone-refractory prostate cancer are also provided.

Compositions and methods for increasing plant yield, either directly or through selective inhibition of competing weeds, are disclosed herein. Particular focus is paid to cell cycle signaling permutations such as mutations in the DP-E2F-Rb cell cycle regulatory pathway, and to permutations in brassinolide pathways as transgenic or small-molecule targets for increasing plant yield.

The present invention relates to methods of identifying patients suffering from various types of cancer who are more likely to respond to treatment with a CDK7 inhibitor conforming to structural Formula (I), (la), a species thereof, or a specified form thereof (as described herein), either when administered or used alone or in combination with a second therapeutic agent (e.g., another anti-cancer therapy). Patients are identified based on one or more features (e.g., gene copy number or expression level) of certain biomarkers (e.g., RB1 or another member of the E2F pathway). In addition, the present invention relates to methods of treating an identified patient with a compound conforming to structural Formula (I), (la), a species thereof, or a specified form thereof, either alone or in combination with a second therapeutic agent. In another aspect, the present invention features kits including instructions for treating a patient identified as described herein.

Fusions of the transcription factor E2F and the retinoblastoma protein RB are provided, along with methods of treatment of hyperproliferative diseases.

The present invention relates to a gene expression regulating sequence consisting of a combination of HRE, E2F and TERT, and to a gene delivery system having significantly improved selective tumor cell cytotoxicity using same, and more particularly, to a recombinant adenovirus. In addition, the present invention relates to a pharmaceutical antitumor composition comprising the recombinant adenovirus. The replication of the recombinant adenovirus of the present invention is tumor-specifically regulated by the novel gene expression regulating sequence of the present invention, thus enabling the recombinant adenovirus of the present invention to exhibit improved selective tumor cell cytotoxicity or apoptotic potential, and exhibit remarkably improved antitumor effects particularly in hypoxic conditions. In addition, the specific expression of the recombinant adenovirus in tumor cells may increase in vivo stability, and thus may induce greatly improved antitumor effects.

Recombinant adenoviruses that selectively replicate in E2F deregulated tumor cells are described. The recombinant adenoviruses have a genome encoding a modified El A protein, a modified or deleted E4orf 1 protein, a modified or deleted E4orf6 / 7 protein, or any combination thereof, such that the recombinant adenoviruses exhibit replication defects in normal cells compared to tumor cells. In some instances, the recombinant adenovirus genomes encode additional modifications that target the recombinant adenoviruses to specific cell types, detarget the viruses from the liver, inhibit viral replication in the liver, and / or evade pre-existing neutralizing antibodies.

The invention discloses a soybean-induced promoter SP2, which belongs to the construction of an artificially synthesized promoter. It uses G-box, ABRE, ABF, SORLIP1, CCA1, and E2F as basic cis elements, and each element repeats four times in series. The elements are separated by a random sequence of 7-9 bases, and the above designed fragments are then connected with the 35S core promoter Core CaMV 35S to construct, named SP2. The identification of the expression of the reporter gene GUS driven by the SP2 promoter in transgenic tobacco showed that the SP2 promoter can be induced by drought, salt, saline-alkali, ABA and low temperature stress, and is extremely sensitive to drought stress. It can be directly applied to crop transgenic stress resistance breeding.

The present invention provides peptides which bind to the DNA binding domain of transcription factor E2F, and inhibit cell cycle progression. Peptides include FWLRFT (SEQ ID NO:1); WVRWHF (SEQ ID NO:2); WHFIFW (SEQ ID NO:3); IWLSGLSRGVWVSFP (SEQ ID NO:4); and GSRILTFRSGSWYAS (SEQ ID NO:5) and derivatives based upon these sequences. Compositions and the use of the peptides in inhibiting cell cycle progression, such as in uncontrolled cell proliferation, are also provided.

This invention relates to hepatic cancer-testis specific anti-genetic protein and anti-genetic peptide. The anti-genetic protein has the amino acid sequence shown in SEQ ID No. 1 (from AA 108-AA 191). The anti-genetic protein and anti-genetic peptide can be used as E2F activity-blocking agent in PRB / E2F signal transduction, and have antagonistic effects on homologous analogue TEDP-1. The tumor antigen protein can decompose in cells to obtain peptide fragments, which can bind with the main histocompatibility complex (MHC)-I molecules, and be recognized by T cells. The anti-genetic protein and anti-genetic peptide can be applied in anti-tumor drugs.

Fusions of the transcription factor E2F and the retinoblastoma protein RB are provided, along with methods of treatment of hyperproliferative diseases.

A high-throughput fluorescence polarization assay to screen molecules for their modulation of Rb-E2F binding affinity.

The present invention provides peptides which bind to the DNA binding domain of transcription factor E2F, and inhibit cell cycle progression. Peptides include FWLRFT (SEQ ID NO:1); WVRWHF (SEQ ID NO:2); WHFIFW (SEQ ID NO:3); IWLSGLSRGVWVSFP (SEQ ID NO:4); and GSRILTFRSGSWYAS (SEQ ID NO:5) and derivatives based upon these sequences. Compositions and the use of the peptides in inhibiting cell cycle progression, such as in uncontrolled cell proliferation, are also provided.

This invention relates to methods, agents and compositions for regulating the neoantigen landscape of cancer cells, based on the realisation that intron retention in a cancer cell can be manipulated. Agents that can modify retained intron neoantigen expression in cancer cells are described, and their use in drug discovery and therapy. One aspect provides an agent for use in a method of treating cancer by modifying the neoantigen profile of at least one cancer cell. The agent may typically be a protein arginine N-methyltransferase 5 (PRMT5) inhibitor, and / or may reduce methylation of an E2F protein, for example E2F1.