Ptc Therapeutics, Inc.

Pct Therapeutics, Inc.

Christopher Robert Trotta

Liangxian Cao

Nikolai A Naryshkin

Charles Romfo

Anuradha Bhattacharyya

Amal Dakka

Thomas W Davis

Panayiota Trifillis

Matthew C Pellegrini

Kari Wiedinger

Wencheng Li

Vijayalakshmi Gabbeta

Kerstin Effenberger

Don Corson

Jeff Campbell

William Lennox

Young-Choon Moon

Neil Gregory Almstead

Jeffrey Allen Campbell

Soongyu Choi

Hongyan Qi

Marla L Weetall

Peter Seongwoo Hwang

Langdon Miller

William Jospeh Lennox

Sergey Paushkin

Donald Thomas Corson

Zhengxian Gu

Minakshi B Jani

Harry H Miao

Jason D Graci

Tamil Arasu

Anuradha Roy

Anuradha Mehta

Matthew C Pelligrini

Charles M Romfo

Thomas Davis

Maria L Weetall

In one aspect, described herein is an intronic recognition element for splicing modifier (iREMS) that can be recognized by a compound provided herein. In another aspect, described herein are methods for modulating the amount of a product of a gene, wherein a precursor RNA transcript transcribed from the gene contains an intronic REMS, and the methods utilizing a compound described herein. More particularly, described herein are methods for modulating the amount of an RNA transcript or protein product encoded by a gene, wherein a precursor RNA transcript transcribed from the gene comprises an intronic REMS, and the methods utilizing a compound described herein. In another aspect, provided herein are artificial gene constructs comprising an intronic REMS, and uses of those artificial gene constructs to modulate protein production. In another aspect, provided herein are methods for altering endogenous genes to comprise an intronic REMS, and the use of a compound described herein to modulate protein produced from such altered endogenous genes.

Methods for modulating RNA splicing

Described herein is an intronic recognition element for splicing modifier (iREMS) that can be recognized by a small molecule splicing modifier compound of Formula (I) provided herein or a form thereof, wherein W, X, A and B are as defined herein. In one aspect, methods for modifying RNA splicing to modulate the amount of a product of a gene, wherein a precursor RNA transcript transcribed from the gene that contains an intronic REMS is modified utilizing a splicing modifier compound of Formula (I), are described herein. In another aspect, methods for modifying RNA splicing to modulate the amount of an RNA transcript or protein product encoded by a gene, wherein a precursor RNA transcript transcribed from the gene is modified to comprise an intronic REMS utilizing a splicing modifier compound of Formula (I), are described herein.

Methods for modifying RNA splicing

The invention relates to the fields of screening assays, compounds, and methods for altering gene expression and protein levels. In particular, the invention includes assays to screen for agents capable of modulating gene expression in a UTR-dependent manner and agents capable of modulating gene expression.

Methods and agents for screening for compounds capable of modulating gene expression

Compounds, such as compounds of Formula (I), that selectively inhibit pathological production of human vascular endothelial growth factor (VEGF) and compositions comprising such Compounds are described. Compounds that inhibit viral replication or the production of viral RNA or DNA or viral protein and compositions comprising such Compounds are described. Also described are methods of reducing VEGF using such Compounds and methods for treating cancer and non-neoplastic conditions involving the administration of such Compounds. Further described are methods of inhibiting viral replication or the production of viral RNA or DNA or viral protein using such Compounds and methods for treating viral infections involving the administration of such Compounds. The Compounds may be administered as a single agent therapy or in combination with one or more additional therapies to a human in need of such treatments. 

Methods for treating cancer and non-neoplastic conditions

The invention relates to the fields of screening assays and compounds and methods for altering protein expression and levels of protein. In particular, the invention includes assays to screen for agents capable of modulating expression of VEGF and agents capable of modulating VEGF expression.

Methods and agents for screening for compounds capable of modulating VEGF expression

The invention provides human protein complexes with endonuclease activity, including tRNA splicing endonuclease activity and 3' end pre-mRNA endonuclease activity, and pre-ribosomal RNA cleavage activity. The invention also provides a splice variant of human Sen2, and human protein complexes comprising the variant. The invention provides human protein complexes with pre-ribosomal RNA cleavage activity. The invention also provides antibodies that immunospecifically bind to a complex described herein or a component thereof, and uses of such antibodies. The present invention also provides methods of preparing and purifying the complexes and uses of the complexes inter alia, in screening, diagnosis, and therapy. The present invention further provides methods of identifying a compound that modulates the expression of a component of a complex described herein, the formation of a complex described herein or the activity of a complex described herein, and methods of preventing, treating, managing or ameliorating a disorder, such as a proliferative disorder, or a symptom thereof utilizing such a compound.

RNA processing protein complexes and uses thereof

In accordance with the present invention, methods for inhibiting the translation of VEGF and methods for decreasing VEGF level by inhibiting VEGF translation are provided. In another aspect of the invention, compounds that inhibit the 5'-UTR-dependent translation of VEGF and methods for identifying such compounds are provided.

Inhibition of VEGF translation

The present invention relates to a method for screening and identifying compounds that modulate the activity tRNA splicing endonuclease. In particular, the invention provides assays for the identification of compounds that inhibit animalia tRNA splicing endonuclease. The methods of the present invention provide a simple, sensitive assay for high-throughput screening of libraries of compounds to identify pharmaceutical leads useful for treating and/or preventing cancer.

Methods of identifying compounds that target tRNA splicing endonuclease and uses of said compounds as anti-proliferative agents

The present invention relates to a method for screening and identifying compounds that modulate the activity of a fungal tRNA splicing endonuclease. In particular, the invention provides assays for the identification of compounds that inhibit or reduce the activity of a fungal tRNA splicing endonuclease. The methods of the present invention provide a simple, sensitive assay for high-throughput screening of libraries of compounds to identify pharmaceutical leads useful for preventing, treating, managing and/or ameliorating a fungal infection or fungal infestation or one or more symptoms thereof.

Methods of identifying compounds that target tRNA splicing endonuclease and uses of said compounds as anti-fungal agents

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Somerset, NJ, United States of America

Christopher Robert Trotta