Ionis Pharmaceuticals, Inc.

University of California

University of Texas System

Isis Pharmaceuticals, Inc.

Shuling Guo

Brett P Monia

Susan M Freier

Andrew M Siwkowski

Punit P Seth

Michael L McCaleb

Eric E Swayze

Michael Oestergaard

Susan F Murray

Nitin Nitin

Noriko Satake

Joseph M Tuscano

Mariam Aghajan

Jacqueline T Hecht

Karen LaShea Posey

Provided herein are methods, compounds, and compositions for reducing expression of transthyretin mRNA and protein in an animal. Such methods, compounds, and compositions are useful to treat, prevent, delay, or ameliorate transthyretin amyloidosis, or a symptom thereof.

Modulation of transthyretin expression

Provided herein are methods, compounds, and compositions for reducing expression of DYRKIB in an animal. Such methods, compounds, and compositions are useful to treat, prevent, delay, or ameliorate a metabolic disease or disorder in an individual in need.

Modulation of DYRK1B expression

Disclosed herein are compositions and compounds comprising modified oligonucleotides for modulating TMPRSS6 and modulating an iron accumulation disease, disorder and/or condition in an individual in need thereof. Iron accumulation diseases in an individual such as polycythemia, hemochromatosis or &#x3b2;-thalassemia can be treated, ameliorated, delayed or prevented with the administration of antisense compounds targeted to TMPRSS6.

Compounds and methods for modulating TMPRSS6 expression

In certain embodiments, hybridization results in modulation of the amount activity or expression of the target nucleic acid in a cell. In certain embodiments, the target nucleic acid is a nucleic acid that encodes cartilage oligomeric matrix protein. In certain embodiments, the target nucleic acid is a nucleic acid expressed in the growth plate, tendon, or cartilage.

Compounds and methods for the modulation of COMP

Disclosed herein are antisense compounds and methods for modulating TMPRSS6 and modulating an iron accumulation disease, disorder and/or condition in an individual in need thereof. Iron accumulation diseases in an individual such as hemochromatosis or &#x3b2;-thalassemia can be ameliorated or prevented with the administration of antisense compounds targeted to TMPRSS6.

Modulation of TMPRSS6 expression

Disclosed herein are methods for decreasing A1AT mRNA and protein expression and treating, ameliorating, preventing, slowing progression, or stopping progression of fibrosis. Disclosed herein are methods for decreasing A1AT mRNA and protein expression and treating, ameliorating, preventing, slowing progression, or stopping progression of liver disease, such as, A1ATD associated liver disease, and pulmonary disease, such as, A1ATD associated pulmonary disease in an individual in need thereof. Methods for inhibiting A1AT mRNA and protein expression can also be used as a prophylactic treatment to prevent individuals at risk for developing a liver disease, such as, A1ATD associated liver disease and pulmonary disease, such as, A1ATD associated pulmonary disease.

Methods and compositions for modulating alpha-1 antitrypsin expression

The present disclosure provides compounds comprising modified oligonucleotides and anti-CD22 antibodies. Certain such modified oligonucleotides conjugated to anti-CD22 antibodies are useful for hybridizing to a complementary nucleic acid, including but not limited, to nucleic acids in a cell. In certain embodiments, hybridization results in modulation of the amount activity or expression of the target nucleic acid in a cell.

Antisense compounds and uses thereof

Disclosed herein are methods for decreasing AIAT mRNA and protein expression and treating, ameliorating, preventing, slowing progression, or stopping progression of fibrosis. Disclosed herein are methods for decreasing AIAT mRNA and protein expression and treating, ameliorating, preventing, slowing progression, or stopping progression of liver disease, such as, AIATD associated liver disease, and pulmonary disease, such as, AIATD associated pulmonary disease in an individual in need thereof. Methods for inhibiting AIAT mRNA and protein expression can also be used as a prophylactic treatment to prevent individuals at risk for developing a liver disease, such as, AIATD associated liver disease and pulmonary disease, such as, AIATD associated pulmonary disease.

Growing community of inventors

Carlsbad, CA, United States of America

Shuling Guo