Other

The Cleveland Clinic Foundation

Paul F Torrence

Robert H Silverman

Guiying Li

Wei Hao Xiao

Nick Mario Cirino

Mark R Player

Seiji Kondo

John K Cowell

Krystyna Lesiak

Ratan K Maitra

The present invention relates to chimeric molecules comprising an oligonucleotide complementary to a region of the ribonucleotide component of telomerase attached to an activator of RNase L (&ldquo;activator-antisense complex&rdquo;) which specifically cleaves the ribonucleotide portion of a telomerase enzyme. The present invention relates to methods of inhibiting telomerase enzymatic activity with activator-antisense complexes targeted to the RNA component of telomerase. The present invention further relates to methods of treating malignant neoplastic disease, wherein the malignant cells contain a telomerase activity that is necessary for the growth of the malignant cells.

RNase L activators and antisense oligonucleotides effective to treat telomerase-expressing malignancies

Chimeric molecules comprising a virus targeting antisense oligonucleotide moiety attached to an activator of 2-5A-dependent RNase.

Chimeric molecules targeted to viral RNAs

The present invention relates to methods of inhibiting infection by RNA viruses with complexes of an activator of RNase L and an oligonucleotide that is capable of binding to the genome, antigenome or mRNAs of a negative strand RNA virus to specifically cleave the genomic or antigenomic RNA strand of the virus. In accordance with the present invention, the methods and complexes of the invention may be applied to target any negative strand RNA virus. The invention in one embodiment relates to a covalently linked complex of an oligonucleotide that is capable of binding to the genomic or antigenomic template RNA strand of a negative strand RNA virus and/or binding to an mRNA of a viral protein (an &ldquo;antisense oligonucleotide&rdquo;) coupled to an activator of RNase L. In a preferred embodiment of the present invention, the oligonucleotide component of the complex is complementary to a region of the viral genomic RNA strand characterized by repeated or consensus sequences.

RNase L activators and antisense oligonucleotides effective to treat RSV infections

The invention concerns a compounds and methods for treating infection with Respiratory Syncytial Virus. The compounds comprise an antisense portion, which is complementary to a normally single stranded portion of the RSV antigenomic strand (the mRNA strand), a linker and a oligonucleotide activator of RNase L, a ubiquitous non-specific RNase. The method comprised forming a complex of an activated RNase L and the antisense molecule. The application teaches methods of determining which portions of the RSV antigenomic strand are normally single-stranded. The application teaches that an antisense oligonucleotide having the sequence of residues 8281-8299 of the RSV genome is particularly useful to practice the invention and provides in vitro results superior to those obtainable with the conventional drug of choice, ribavirin.

RNase L activators and antisense oligonucleotides effective to treat RSV

Growing community of inventors

Silver Spring, MD, United States of America

Paul F Torrence