Alcon Research, Ltd.

Arrowhead Pharmaceuticals, Inc.

Arrowhead Research Corporation

Novartis Ag

Alcon, Inc.

Thermo Fisher Scientific Gmbh

Thermo Fisher Scientific Biosciences Inc.

John M. Yanni

Steven T. Miller

Ltd. Alcon Manufacturing

Jon E. Chatterton

Daniel A. Gamache

Jon E Chatterton

Abbot F Clark

John M Yanni

Daniel A Gamache

Steven T Miller

Martin B Wax

David P Bingaman

Wan-Heng Wang

Loretta Graves McNatt

Adrian M Timmers

Diane Michelle Senchyna

Angela Reynolds

Anja Smith

Ying Yu

Xinyu Zhang

Allan R Shepard

The invention provides interfering RNA molecule-ligand conjugates useful as a delivery system for delivering interfering RNA molecules to a cell in vitro or in vivo. The conjugates comprise a ligand that can bind to a transferrin receptor (TfR). Therapeutic uses for the conjugates are also provided.

Transferrin/transferrin receptor-mediated siRNA delivery

The invention provides a delivery system comprising a cell penetrating peptide, 10 histidines, and an interfering RNA molecule. The system can be used for delivering interfering RNA molecules into a cell in vivo or in vitro. Therapeutic uses for the delivery system are also provided.

Interfering RNA delivery system and uses thereof

The invention provides a delivery system comprising a cell penetrating peptide, a polyarginine peptide, and an interfering RNA molecule. The system can be used for delivering interfering RNA molecules into a cell in vivo or in vitro. Therapeutic uses for the delivery system are also provided.

RNA interference is provided for inhibition of phosphodiesterase type 4 mRNA expression for treating patients with a cAMP-related ocular disorder. Phosphodiesterase type 4 mRNA targets include mRNA for 4A, 4B, 4C, and 4D phosphodiesterase isoforms.

RNAi-mediated inhibition of phosphodiesterase type 4 for treatment of CAMP-related ocular disorders

RNA interference is provided for inhibition of connexin 43 (Cx43) in intraocular pressure-related conditions, including ocular hypertension and glaucoma such as normal tension glaucoma and open angle glaucoma.

RNAi-mediated inhibition of connexin 43 for treatment of IOP-related conditions

RNA interference is provided for inhibition of histamine receptor H1 mRNA expression, in particular, for treating patients having an HRH1-related condition or at risk of developing an HRH1-related condition such as allergic conjunctivitis, ocular inflammation, dermatitis, rhinitis, asthma, or allergy.

RNAi-mediated inhibition of histamine receptor H1-related conditions

RNA interference is provided for inhibition of Frizzled Related Protein-1 mRNA expression, in particular, for treating patients having glaucoma or at risk of developing glaucoma.

RNAI-mediated inhibition of frizzled related protein-1 for treatment of glaucoma

The invention provides interfering RNA molecule-ligand conjugates useful as a delivery system for delivering interfering RNA molecules to a cell in vitro or in vivo. The conjugates comprise a ligand that can bind to a low density lipoprotein receptor (LDLR) or LDLR family member. Therapeutic uses for the conjugates are also provided.

Low density lipoprotein receptor-mediated siRNA delivery

RNA interference is provided for inhibition of tumor necrosis factor &#x3b1; (TNF&#x3b1;) by silencing TNF&#x3b1; cell surface receptor TNF receptor-1 (TNFR1) mRNA expression, or by silencing TNF&#x3b1; converting enzyme (TACE/ADAM17) mRNA expression. Silencing such TNF&#x3b1; targets, in particular, is useful for treating patients having a TNF&#x3b1;-related condition or at risk of developing a TNF&#x3b1;-related condition such as the ocular conditions dry eye, allergic conjunctivitis, or ocular inflammation, or such as dermatitis, rhinitis, or asthma, for example.

RNAi-mediated inhibition of tumor necrosis factor &#x3b1;-related conditions

RNA interference is provided for inhibition of tumor necrosis factor &#x3b1; (TNF&#x3b1;) by silencing TNF&#x3b1; cell surface receptor TNF receptor-1 (TNFR1) mRNA expression, or by silencing TNF&#x3b1; converting enzyme (TACE/ADAM17) mRNA expression. Silencing such TNF&#x3b1; targets, in particular, is useful for treating patients having a TNF&#x3b1;-related condition or at risk of developing a TNF&#x3b1;-related condition, such as ocular angiogenesis, retinal ischemia, and diabetic retinopathy.

RNAi-related inhibition of TNF-alpha signaling pathway for treatment of ocular angiogenesis

RNA interference is provided for inhibition of spleen tyrosine kinase (Syk) mRNA expression, in particular, for treating patients having a Syk-related inflammatory condition or at risk of developing a Syk-related inflammatory condition such as allergic conjunctivitis, ocular inflammation, dermatitis, rhinitis, asthma, allergy, or mast-cell disease.

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Fort Worth, TX, United States of America

Jon E Chatterton