Duke University

Other

Ribonomics, Inc.

Emory University

The Rockfeller University

Jack D Keene

Scott A Tenenbaum

Craig C Carson

Todd Levine

FenBiao Gao

Peter H King

Rex O Bentley

Charles C Query

Robert Darnell

Stephen T Warren

Peng Jin

Victoria Brown-Kennerly

William C Phelps

Stephanie Ceman

Jennifer C Darnell

Donald E Tsai

Patrick J Lager

Daniel J Kenan

Patrick Lager

A method of generating a gene expression profile of noncoding regulatory RNA (ncRNA; e.g. a microRNA) in a cell in vivo, is carried out by: (a) partitioning from a cell at least one mRNA-protein (RNP) complex, the RNP complex comprising: (i) an RNA binding protein (RNABP) or RNA associated protein, (ii) at least one mRNA bound to or associated with said protein, and (iii) at least one ncRNA bound to or associated with said protein, and then (b) identifying at least one ncRNA in-at least one RNP complex, thereby to produce a gene expression profile comprising the identity of an ncRNA in an RNP complex.

Methods for in vivo identification of endogenous mRNA targets of MicroRNAs

The identification and evaluation of mRNA and protein targets associated with mRNP complexes and implicated in the expression of proteins involved in common physiological pathways is described. Effective targets are useful for treating a disease, condition or disorder associated with the physiological pathway.

Methods for identifying functionally related genes and drug targets

Cellular mRNA-protein (mRNP) complexes are partitioned in vivo by contacting a biological sample with at least one ligand that specifically binds at least one component of a mRNP complex. Suitable biological samples comprise at least one mRNA-protein (mRNP) complex and include cell cultures, cell extracts, and whole tissue, including tumor tissue. Ligands include antibodies that specifically bind RNA-binding or RNA-associated proteins present in the mRNP complex. The mRNP complex is separated by binding the ligand with a binding molecule specific for the ligand, where the binding molecule is attached to a solid support. The mRNP complex is collected by removing the mRNP complex from the solid support. After collecting the mRNP complex, the mRNA bound within the complex may be characterized and identified. Subsets of the total mRNA population of a cell may accordingly be characterized, and a gene expression profile of the cell obtained.

Methods for isolating and characterizing endogenous mRNA-protein (mRNP) complexes

Compositions and methods for identifying and/or modulating RNA transcripts and/or genes involved in fragile X syndrome and other associated disorders are provided. In particular, RNA targets for fragile X mental retardation protein (FMRP) have been identified by a novel monoclonal antibody to FMRP and a consensus sequence for the RNA binding region has been identified. Arrays for identifying compounds, proteins, nucleotides, and the like that modulate the RNA targets or associated genes are provided. Additionally, methods for modulating RNA targets are provided.

Method and identification of downstream mRNA ligands to FMRP and their role in fragile X syndrome and associated disorders

A method of generating a nucleic acid species which are immunologically cross-reactive with non-nucleic acid immunogens is disclosed. The method comprises combining an antigen binding protein which binds said immunogen with a degenerate pool of nucleic acid species, and then recovering a nucleic acid species bound by said antigen binding protein from said degenerate pool. Also disclosed are the nucleic acid species so made, along with the use thereof for tagging molecules for immunological detection, for detecting antibodies to predetermined non-nucleic acid immunogens, for blocking complex formation between an antigen binding protein and a non-nucleic acid immunogen, and for inducing an immune response to the immunogen in a human or animal subject. Preferred immunogens are peptides and preferred antigen binding proteins are antibodies.

Method for deriving epitopes

Methods of making nucleic acids that inhibit complex formation between antigen binding proteins and non-nucleic acid immunogens are provided. Methods of making non-nucleic acid immunogens that inhibit complex formation between antigen binding proteins and nucleic acids are also provided herein.

Method of isolating ribotopes and proteotopes

Ribonucleoproteins and RNA-binding proteins related to the amino acid sequence corresponding at least to residues 92 to 202 and up to about residues 1 to about 240 of sequence (III), or of a modification of such sequences (III) having at least 35% homology with sequence (III) are disclosed. Sequence (III) is: ##STR1##

Ribonucleoproteins and RNA-binding proteins useful for the specific

Methods and compounds are described that allow partitioning of messenger RNAs encoding runctionally related proteins, in particular those involved in cellular growth and differentiation, based upon binding to target sequences in the untranslated portions of the RNAS. The preparation of mRNA-subset libraries containing genes encoding such growth regulatory factors is described together with novel gene sequences derived useing these mRNA partitioning methods. These methods of mRNA partitioning allow access to growth regulatory factors unique to a given cell, tissue or tumor and provide a method of fingerprinting such factors.

Methods and compositions useful in the recognition, binding and

A method for producing a protein antigen which is reactive with an autoantibody associated with an autoimmune disease in a host, which comprises introducing genetic information from a cross-reactive donor gene library, into plural cells thereby producing transformed cells; selecting a producer cell which expresses said antigen by detecting a binding reaction between said autoantibody obtained from said host and a protein antigen expressed by a producer cell of said transformed cells which contains a gene coding for said protein antigen, thereby identifying a cloned DNA segment from said donor which can be utilized in the production of said protein, is disclosed along with biochemical reagents and products associated with this invention.

Methods and compositions useful in the diagnosis and treatment of

A peptide, Hel-N1, which can bind to a 3'-untranslated mRNA sequence (which encompasses the 'instability sequence') that is uniquely present in the messenger RNAs that encode oncoproteins and lymphokines, and mediates the specific destruction of the messenger RNAs, is described. Full-length Hel-N1 is capable of suppressing cell growth and causing cellular differentiation. Hel-N1 possess three RNA recognition motifs. One of these forms an RNA-binding domain which, when transfected alone into cells, causes them to undergo rapid growth.

Methods and compositions involved in cell growth, neoplasia and

Ribonucleoproteins and DNA-binding proteins related to the amino acid sequence corresponding at least to residues 92-202 and up to about residues 1 to about 240 of sequence (III), or of a modification of such sequences (III) having at least 35% homology with sequence (III) are disclosed.

RNA-binding proteins useful for the control of cellular genetic

A method for producing a protein antigen which is reactive with an autoantibody associated with an autoimmune disease in a host, which comprises introducing genetic information from a cross-reactive donor gene library, into plural cells thereby producing transformed cells: selecting a producer cell which expresses said antigen by detecting a binding reaction between said autoantibody obtained from said host and a protein antigen expressed by a producer cell of said transformed cells which contains a gene coding for said protein antigen, thereby identifying a cloned DNA segment from said donor which can be utilized in the production of said protein, is disclosed along with biochemical reagents and products associated with this invention.

Growing community of inventors

Durham, NC, United States of America

Jack D Keene