Protiva Biotherapeutics, Inc.

Arbutus Biopharma Corporation

Other

Amy C H Lee

Ian MacLachlan

Adam Judge

Marjorie Ann Robbins

James Heyes

Mark Wood

Alan Martin

Vandana Sood

Nicholas Michael Snead

Emily P Thi

Richard James Holland

Thomas W Geisbert

Lisa E Hensley

Marcia MacDonald

Ammen P Dhillon

Ed Yaworski

Nicholas D Weber

Xin Ye

Jennifer L Cross

Ian Maclachlan

The invention provides certain nucleic acids (e.g., double stranded siRNA molecules), as well as conjugates that comprise a targeting moiety, a double stranded siRNA, and optional linking groups. Certain embodiments also provide synthetic methods useful for preparing the conjugates. The conjugates are useful to target therapeutic double stranded siRNA to the liver and to treat liver diseases including hepatitis (e.g. hepatitis B and hepatitis D).

Targeted compositions

The present invention provides lipid particles comprising therapeutic nucleic acids such as gRNA that target gene expression.

Delivering CRISPR therapeutics with lipid nanoparticles

The present invention provides compositions comprising therapeutic nucleic acids such as siRNA that target Hepatitis B virus (HBV) gene expression, lipid particles comprising one or more (e.g., a combination) of the therapeutic nucleic acids, and methods of delivering and/or administering the lipid particles (e.g., for treating HBV infection and/or HDV infection in humans).

Compositions and methods for silencing hepatitis B virus gene expression

The present invention provides compositions comprising therapeutic nucleic acids such as interfering RNA that target apolipoprotein C-III (APOC3) gene expression, lipid particles comprising one or more (e.g., a cocktail) of the therapeutic nucleic acids, methods of making the lipid particles, and methods of delivering and/or administering the lipid particles (e.g., for the treatment of lipid diseases or disorders such as atherosclerosis or a dyslipidemia such as hypertriglyceridemia or hypercholesterolemia).

Compositions and methods for silencing apolipoprotein C-III expression

The present invention provides compositions comprising therapeutic nucleic acids (e.g., interfering RNA such as siRNA) that target Ebola virus (EBOV) gene expression and methods of using such compositions to silence EBOV gene expression. More particularly, the invention provides unmodified and chemically modified interfering RNA which silence EBOV gene expression and methods of use thereof, e.g., for preventing or treating EBOV infections caused by one or more EBOV species such as Zaire EBOV. The invention also provides serum-stable nucleic acid-lipid particles comprising one or more interfering RNA molecules, a cationic lipid, and a non-cationic lipid, which can further comprise a conjugated lipid that inhibits aggregation of particles. Methods of silencing EBOV gene expression by administering one or more interfering RNA molecules to a mammalian subject are also provided.

Compositions and methods for silencing ebola virus gene expression

The present invention provides compositions comprising therapeutic nucleic acids such as interfering RNA (e.g., dsRNA such as siRNA) that target SMAD4 gene expression, lipid particles comprising one or more (e.g., a cocktail) of the therapeutic nucleic acids, methods of making the lipid particles, and methods of delivering and/or administering the lipid particles (e.g., for treating anemia of inflammation in humans).

Compositions and methods for silencing SMAD4

The present invention provides compositions comprising therapeutic nucleic acids such as interfering RNA (e.g., dsRNA such as siRNA) that target aldehyde dehydrogenase (ALDH) gene expression, lipid particles comprising one or more (e.g., a cocktail) of the therapeutic nucleic acids, methods of making the lipid particles, and methods of delivering and/or administering the lipid particles (e.g., for treating alcoholism in humans).

Compositions and methods for silencing aldehyde dehydrogenase

The present invention provides compositions and methods for the delivery of interfering RNAs such as siRNAs that silence APOB expression in cells such as liver cells. In particular, the nucleic acid-lipid particles provide efficient encapsulation of nucleic acids and efficient delivery of the encapsulated nucleic acid to cells such as liver cells in vivo. The compositions of the present invention are highly potent, thereby allowing effective knock-down of APOB at relatively low doses. In addition, the compositions and methods of the present invention are less toxic and provide a greater therapeutic index compared to compositions and methods previously known in the art.

Compositions and methods for silencing apolipoprotein B

Compositions and methods for silencing Ebola virus gene expression

The present invention provides compositions and methods for the delivery of interfering RNAs that silence APOB expression to liver cells. In particular, the nucleic acid-lipid particles provide efficient encapsulation of nucleic acids and efficient delivery of the encapsulated nucleic acid to cells in vivo. The compositions of the present invention are highly potent, thereby allowing effective knock-down of APOB at relatively low doses. In addition, the compositions and methods of the present invention are less toxic and provide a greater therapeutic index compared to compositions and methods previously known in the art.

The present invention provides chemically modified siRNA molecules and methods of using such siRNA molecules to silence target gene expression. Advantageously, the modified siRNA of the present invention is less immunostimulatory than its corresponding unmodified siRNA sequence and retains RNAi activity against the target sequence. The present invention also provides nucleic acid-lipid particles comprising a modified siRNA, a cationic lipid, and a non-cationic lipid, which can further comprise a conjugated lipid that inhibits aggregation of particles. The present invention further provides methods of silencing gene expression by administering a modified siRNA to a mammalian subject. Methods for identifying and/or modifying an siRNA having immunostimulatory properties are also provided.

Growing community of inventors

Burnaby, Canada

Amy C H Lee