Phio Pharmaceuticals Corp.

Rxi Pharmaceuticals Corporation

Pamela A Pavco

Anastasia Khvorova

Tod M Woolf

Joanne Kamens

William Salomon

James Cardia

Dmitry Samarsky

Lyn Libertine

Karen G Bulock

Michael Francis Byrne

Gerard Cauwenbergh

Karen Gunn Bulock

The present invention relates to ocular administration of sd-rxRNA and rxRNAori molecules.

RNA interference in ocular indications

Aspects of the invention relate to methods for treating ALS comprising administering to a subject in need thereof a therapeutically effective amount of a nucleic acid molecule that is directed against a gene encoding superoxide dismutase 1 (SOD1).

Nucleic acid molecules targeting superoxide dismutase 1 (SOD1)

The present invention relates to RNAi constructs with improved tissue and cellular uptake characteristics and methods of use of these compounds in dermal and fibrotic applications.

RNA interference in dermal and fibrotic indications

The present invention relates to RNAi constructs with improved tissue and cellular uptake characteristics and methods of use of these compounds in dermal applications.

RNA interference in skin indications

The invention related to improved RNAi constructs and uses thereof. The construct has a double stranded region of 19-49 nucleotides, preferably 25, 26, or 27 nucleotides, and preferable blunt-ended. The construct has selective minimal modifications to confer an optimal balance of biological activity, toxicity, stability, and target gene specificity. For example, the sense strand may be modified (e.g., one or both ends of the sense strand it/are modified by four 2'&#x2014;O-mehtyl groups), such that the construct is not cleaved by Dicer or other RNAse III, and the entire length of the antisense strand is loaded into RISC. In addition, the antisense strand may also be modified by 2&#x2032;&#x2014;O-methyl group at the 2nd 5&#x2032;-end nucleotide to greatly reduce off-target silencing. The constructs of the invention largely avoids the interferon response and sequence-independent apoptosis in mammalian cells, exhibits better serum stability, and enhance target specificity.

Modified RNAi polynucleotides and uses thereof

The invention relates to improved RNAi constructs and uses thereof. The construct has a double stranded region of 19-49 nucleotides, preferably 25, 26, or 27 nucleotides, and preferably blunt-ended. The construct has selective minimal modifications to confer an optimal balance of biological activity, toxicity, stability, and target gene specificity. For example, the sense strand may be modified (e.g., one or both ends of the sense strand is/are modified by four 2'-O-methyl groups), such that the construct is not cleaved by Dicer or other RNAse III, and the entire length of the antisense strand is loaded into RISC. In addition, the antisense strand may also be modified by 2&#x2032;-O-methyl group at the 2nd 5&#x2032;-end nucleotide to greatly reduce off-target silencing. The constructs of the invention largely avoids the interferon response and sequence-independent apoptosis in mammalian cells, exhibits better serum stability, and enhanced target specificity.

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Longmont, CO, United States of America

Pamela A Pavco