Abstract: The invention described herein allows the production of recombinant retroviruses (retroviral vector particles) from producer cells which are safer and of higher titer than normal. In addition, methods are provided for making helper cells which, when a recombinant retrovirus genome is introduced to make a producer line, produce particles that are targeted toward particular cell types. Methods are also provided for making recombinant retrovirus systems adapted to infect a particular cell type, such as a tumor, by binding the retrovirus or recombinant retrovirus in the particular cell type. Methods are also provided for producing recombinant retroviruses which integrate in a specific small number of places in the host genome, and for producing recombinant retroviruses from transgenic animals.

Abstract: The invention provides ribozymes and encoding nucleic acids having target recognition sequences that allow the ribozyme to target and cleave BRCA-1 regulators, resulting in upregulation of BRCA-1 in a cell. Also provided are nucleic acids encoding BRCA-1 regulators that contain the target sequences recognized by the ribozymes of the invention. Fragments of these nucleic acid and protein sequences also are provided. Further provided is a method for identifying a gene where the expression level is affected by a BRCA-1 regulator and the identity of several such affected genes. Still further provided is a method of identifying a compound that modulates the activity of a BRCA-1 regulator. Also provided is a method of treating cancer, comprising introducing a ribozyme selectively reactive with an RNA encoding a BRCA-1 regulator into a cancerous cell. The invention further comprises a method of detecting a neoplastic cell in a sample.

Abstract: A method of identifying a compound that modulates the activity of a cellular regulator is provided. The method consists of contacting a sample containing a cellular regulator and a nucleic acid element acted on by the cellular regulator with a test compound under conditions that allow replication or expression of the nucleic acid element or a gene or MRNA operatively linked to the nucleic acid element or gene, and an increase or decrease in the amount of replication or expression in the presence of the test compound compared to the absence of the test compound indicates that the compound has cellular regulator modulatory activity. A method of treating a HCV infection is also provided.

Abstract: The present invention provides a high complexity substantially complete hairpin ribozyme library having a randomized recognition sequence, packaged in a vector and operably linked to a promoter suitable for high level expression in a wide variety of cells. The invention comprises using the library in a variety of selection protocols for identifying, isolating and characterizing known or unknown target RNAs, to reveal the phenotypic effects of such cleavage, and to identify the gene products that produce those phenotypic effects.

Abstract: The present invention provides genes, nucleic acid sequences, proteins and amino acid sequences that are, involved in the inhibition of apoptosis induction in cells. The invention also provides the RNA correlates of these genes and nucleic acid sequences. Further provided are isolated nucleic acid molecules that interact with the genes, nucleic acid sequences and RNA correlates disclosed herein, such that their inhibitory effect on apoptosis induction is lessened and, therefore, apoptosis induction is facilitated.

Abstract: The present invention discloses compositions, systems and methods for identifying anti-cancer agents using doth in vitro and in vivo techniques. Embodiments include the screening of combinatorial libraries of peptides, antibodies, and small organic molecules as well as siRNAs, ribozymes and antisense nucleotides directed against nucleic acids encoding the GPR 39 protein.

Abstract: The present invention provides a high complexity substantially complete hairpin ribozyme library having a randomized recognition sequence, packaged in a vector and operably linked to a promoter suitable for high level expression in a wide variety of cells. The invention comprises using the library in a variety of selection protocols for identifying, isolating and characterizing known or unknown target RNAs, to reveal the phenotypic effects of such cleavage, and to identify the gene products that produce those phenotypic effects.

Abstract: Methods of inhibiting HIV infection by blocking HIV co-receptor RNA expression are provided. Ribozymes which cleave HIV co-receptor RNA and inhibit HIV infection of cells are also provided. Co-receptor targets include fusin and CKR5.

Abstract: GUC and GUA ribozymes which cleave HIV RNA are provided. The ribozymes cleave HIV RNA in vitro and in vivo. When the ribozymes are expressed in cells, they inhibit HIV replication in the cells.