University of Texas System

Urocor, Inc.

David W Russell

Joseph L Goldstein

Michael S Brown

Thomas C Sudhof

Steven L McKnight

Anice E Thigpen

David W Martin, Jr

Sefan Andersson

Hui Tian

Erik G Lund

Stefan Andersson

The invention provides methods and compositions relating to cholesterol 25-hydroxylase polypeptides having cholesterol 25-hydroxylase-specific structure and activity, related polynucleotides and modulators of cholesterol 25-hydroxylase function and serum cholesterol. The invention provides isolated cholesterol 25-hydroxylase hybridization probes and primers capable of specifically hybridizing with natural cholesterol 25-hydroxylase genes, cholesterol 25-hydroxylase-specific binding agents such as specific antibodies, agonists and antagonists, and methods of making and using the subject compositions in diagnosis (e.g. genetic hybridization screens for cholesterol 25-hydroxylase transcripts), therapy (e.g. cholesterol 25-hydroxylase inhibitors to modulate serum cholesterol) and in the biopharmaceutical industry (e.g. as immunogens, reagents for isolating natural 25-hydroxylase genes and transcripts, reagents for screening chemical libraries for lead pharmacological agents, etc.).

Cholesterol 25-hydroxylase

Disclosed are diagnostic techniques for the detection of human prostate cancer. Genetic probes and methods useful in monitoring the progression and diagnosis of prostate cancer are described. The invention relates particularly to probes and methods for evaluating the presence of RNA species that are differentially expressed in prostate cancer compared to normal human prostate or benign prostatic hyperplasia.

Biomarkers for the detection of prostate cancer

Biomarkers for detection of prostate cancer

The invention provides methods and compositions relating to neuronal PAS domain proteins (NPAS) and related nucleic acids. The proteins may be produced recombinantly from transformed host cells from the disclosed NPAS encoding nucleic acids or purified from human cells. The invention provides isolated NPAS hybridization probes and primers capable of specifically hybridizing with the disclosed NPAS gene, NPAS-specific binding agents such as specific antibodies, and methods of making and using the subject compositions in diagnosis, therapy and in the biopharmaceutical industry.

Neuronal bHLH-PAS domain proteins

The invention provides methods and compositions relating to endothelial PAS domain protein 1 (EPAS1) and related nucleic acids. The proteins may be produced recombinantly from transformed host cells from the disclosed EPAS1 encoding nucleic acids or purified from human cells. The invention provides isolated EPAS1 hybridization probes and primers capable of specifically hybridizing with the disclosed EPAS1 gene, EPAS1-specific binding agents such as specific antibodies, and methods of making and using the subject compositions in diagnosis, therapy and in the biopharmaceutical industry.

Endothelial PAS domain protein

Disclosed are methods and compositions for the preparation of steroid 5.alpha.-reductases by recombinant means, as well as for the use of these enzymes in screening assays for the identification of compounds which have the ability to inhibit or otherwise alter the enzymatic function of these enzymes. Biochemical and pharmacological evidence is presented to demonstrate the existence of more than one human steroid 5.alpha.-reductase. The DNA sequence encoding steroid 5.alpha.-reductase 2, the major active isozyme of human genital tissue, is disclosed herein, in addition to methods and compositions for its preparation and pharmacological analysis. The sequences disclosed herein may be used directly in the preparation of genetic constructs, or may be employed in the preparation of hybridization probes for the selection of enzyme-encoding sequences from other sources. These sequences may prove useful in an analysis of normal and abnormal sexual differentiation, benign prostatic hyperplasia, male pattern baldness, acne, hirsutism, endometriosis, and cancer of the prostate.

Steroid 5A-reductases

Steroid 5a reductase nucleic acid segments and recombinant vectors and

Disclosed are discreet functionally translocatable DNA segments, termed Sterol Regulatory Elements (SRE's) , which are fused to heterologous structural genes to provide sterol regulatory capability to the thus formed hybrid gene. The hybrid genes respond to sterols by decreasing the production of messenger RNA. The SRE segments contain as their primary functional nucleotide sequence, a 16 bp sequence referred to as direct repeats 2, isolated from the 5' regions of the human LDL receptor gene. DNA segments which include this 16 nucleotide long sequence similarly confer sterol regulatory capability to previously known promoters such as the HSV TK promoter. Also disclosed are discreet sequences which confer positive transcription promotion to heterologous structural genes and promoters without conferring sterol responsivity. Methods are disclosed for employing these genetic control elements in a myriad of embodiments which provide for a fine-tune control of heterologous genes. Methods are also disclosed for employing the SRE in a screening assay for drugs capable of stimulating the cell to synthesize LDL receptors.

Method and composition for identifying substances which activate

Disclosed are discrete functionally translocatable DNA segments, termed Sterol Regulatory Elements (SREs), which are fused to heterologous structural genes to provide sterol regulatory capability to the thus formed hybrid gene. The hybrid genes respond to sterols by decreasing the production of messenger RNA. The SRE segments contain as their primary functional nucleotide sequence, a 16 bp sequence referred to as direct repeat 2, isolated from the 5' regions of the human LDL receptor gene. DNA segments which include this 16 nucleotide long sequence similarly confer sterol regulatory capability to previously known promoters such as the HSV TK promoter. Also disclosed are discrete sequences which confer positive transcription promotion to heterologous structural genes and promoters without conferring sterol responsivity. Methods are disclosed for employing these genetic control elements in a myriad of embodiments which provide for a fine-tune control of heterologous genes. Methods are also disclosed for employing the SRE in a screening assay for drugs capable of stimulating the cell to synthesize LDL receptors.

Sterol Regulatory Elements

Disclosed are discreet functionally translocatable DNA segments, termed Sterol Regulatory Elements (SRE's), which are fused to heterologous structural genes to provide sterol regulatory capability to the thus formed hybrid gene. The hybrid genes respond to sterols by decreasing the production of messenger RNA. The SRE segments contain as their primary functional nucleotide sequence, a 16 bp sequence referred to as direct repeat 2, isolated from the 5' regions of the human LDL receptor gene. DNA segments which include this 16 nucleotide long sequence similarly confer sterol regulatory capability to previously known promoters such as the HSV TK promoter. Also disclosed are discreet sequences which confer positive transcription promotion to heterologous structural genes and promoters without conferring sterol responsivity. Methods are disclosed for employing these genetic control elements in a myriad of embodiments which provide for a fine-tune control of heterologous genes. Methods are also disclosed for employing the SRE in a screening assay for drugs capable of stimulating the cell to synthesize LDL receptors.

Host cells transformed with sterol regulatory elements

Recombinant DNA transfer vectors containing DNA inserts which are complementary to either the human LDL receptor gene, or its mRNA transcript, are disclosed. Also disclosed are methods which utilize these genetic probes for diagnosing Familial Hypercholesterolemia (FH) in a suspected individual. A case study of numerous such individual are disclosed wherein the genetic deletion mutation is detailed with great precision through the practice of this invention.

Methods and compositions for the detection of familial

Disclosed are discreet functionally translocatable DNA segments, termined Sterol Regulatory Elements (SRE's), which are fused to heterologous structural genes to provided sterol regulatory capability to the thus formed hybrid gene. The hybrid genes respond to sterols by decreasing the production of messenger RNA. The SRE segments contain as their primary functional nucleotide sequence, a 16 bp sequence referred to as direct repeat 2, isolated from the 5' regions of the human LDL receptor gene. DNA segments which include this 16 nucleotide long sequence similarly confer sterol regulatory capability to previously known promoters such as the HSV TK promoter. Also disclosed are discreet sequences which confer positive transcription promotion to heterologous structural genes and promoters without conferring sterol responsivity. Methods are disclosed for employing these genetic control elements in a myriad of embodiments which provide for a fine-tune control of heterologous genes. Methods are also disclosed for employing the SRE in a screening assay for drugs capable of stimulating the cell to synthesize LDL receptors.

Sterol regulatory elements

Recombinant DNA transfer vectors containing DNA inserts which are complementary to either the human LDL receptor gene, or its mRNA transcript, are disclosed. Also disclosed are methods which utilize these genetic probes for diagnosing Familial Hypercholesterolemia (FH) in a suspected individual. A case study of one such individual, FH 274, is disclosed wherein the genetic deletion mutation is detailed with great precision through the practice of this invention.

Growing community of inventors

Dallas, TX, United States of America

David W Russell