Abstract: Compounds and methods for modulating cell proliferation, preferably inhibiting the proliferation of tumor cells are described. Compounds that may be used to modulate cell proliferation include antisense oligonucleotides complementary to regions of the mammalian ribonucleotide reductase genes.
Abstract: A method for introducing a site-specific mutation into a target polynucleotide sequence is presented. The method involves the use of an oligonucleotide capable of binding to the target sequence, either by triplex formation (mediated by Hoogsteen, reverse Hoogsteen or equivalent base pairing) or by Watson/Crick base pairing (in the presence of a recombinase enzyme). The oligonucleotide of the invention is modified by the covalent attachment of one or more electrophilic groups. When a modified oligonucleotide is bound to its target sequence, the electrophilic group is able to interact with a nearby nucleotide in the target sequence, causing a modification to the nucleotide that results in a change in nucleotide sequence. Compositions used in the practice of the method are also disclosed.
Type:
Grant
Filed:
March 26, 1997
Date of Patent:
October 24, 2000
Assignee:
Epoch Pharmaceuticals, Inc.
Inventors:
Rich B. Meyer, Jr., Howard B. Gamper, Igor V. Kutyavin, Alexander A. Gall
Abstract: Compositions and methods for the treatment and diagnosis of diseases or disorders amenable to treatment through modulation of expression of a nucleic acid encoding a platelet endothelial cell adhesion molecule-1 (PECAM-1; also known as CD31 antigen or endoCAM) protein are provided.
Type:
Grant
Filed:
March 19, 1998
Date of Patent:
September 21, 1999
Assignee:
Isis Pharmaceuticals Inc.
Inventors:
C. Frank Bennett, Thomas P. Condon, Shin Cheng Flournoy, Hong Zhang
Abstract: Novel genetic constructs and methods for their use in transforming target cells are disclosed. The genetic constructs, which are particularly adapted for homologous recombination with target-cell genomes, comprise a positively selectable genetic marker and a negative selection system "antagonistic" to the expression of the positively selectable marker. The positively selectable marker is situated in a region of the construct between a first and a second flanking sequence homologous to sequences flanking a desired integration site in the target-cell genome. The negative selection system is situated outside the region. The negative selection system preferably comprises an antisense gene that prevents expression of the positively selectable marker. The positively selectable marker preferably encodes an antibiotic resistance factor.