The patent badge is an abbreviated version of the USPTO patent document. The patent badge does contain a link to the full patent document.

The patent badge is an abbreviated version of the USPTO patent document. The patent badge covers the following: Patent number, Date patent was issued, Date patent was filed, Title of the patent, Applicant, Inventor, Assignee, Attorney firm, Primary examiner, Assistant examiner, CPCs, and Abstract. The patent badge does contain a link to the full patent document (in Adobe Acrobat format, aka pdf). To download or print any patent click here.

Date of Patent:
Jan. 01, 2019

Filed:

Oct. 06, 2016
Applicant:

Rxi Pharmaceuticals Corporation, Marlborough, MA (US);

Inventors:

Joanne Kamens, Newton, MA (US);

Anastasia Khvorova, Westborough, MA (US);

Assignee:

RXi Pharmaceuticals Corporation, Marlborough, MA (US);

Attorney:
Primary Examiner:
Int. Cl.
CPC ...
C12N 15/85 (2006.01); C07H 21/02 (2006.01); C07H 21/04 (2006.01); C12N 15/113 (2010.01);
U.S. Cl.
CPC ...
C12N 15/1137 (2013.01); C12Y 304/21112 (2013.01); C12N 2310/14 (2013.01); C12N 2310/315 (2013.01); C12N 2310/321 (2013.01); C12N 2310/322 (2013.01); C12N 2310/344 (2013.01); C12N 2310/3515 (2013.01); C12N 2310/531 (2013.01); C12N 2320/11 (2013.01); C12Y 304/21061 (2013.01);
Abstract

The invention relates to various PCSK9 RNAi constructs with gene silencing activities, 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. The sense strand may be modified 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'-O-methyl groups at the 2nd 5′-end nucleotide to greatly reduce off-target silencing. The constructs of the invention largely avoid the interferon response and sequence-independent apoptosis in mammalian cells, exhibits better serum stability, and enhanced target specificity.


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