Sangamo Therapeutics, Inc.

Other

Gary K Lee

David Paschon

Lei Zhang

Brigit E Riley

Anthony Conway

Edward J Rebar

Thomas Wechsler

Susan J St Martin

Sumiti Jain

The present disclosure is in the field of genome engineering, particularly targeted genetic modification of a CISH gene.

Genetic modification of cytokine inducible SH2-containing protein (CISH) gene

Disclosed herein are methods and compositions for inactivating TCR and/or HLA genes, using engineered nucleases comprising at least one DNA binding domain and a cleavage domain or cleavage half-domain in conditions able to preserve cell viability. Polynucleotides encoding nucleases, vectors comprising polynucleotides encoding nucleases and cells comprising polynucleotides encoding nucleases and/or cells comprising nucleases are also provided.

Targeted disruption of T cell and/or HLA receptors

Described herein are constructs used for liver-specific expression of a transgene.

Liver-specific constructs factor VIII expression cassettes and methods of use thereof

Disclosed herein are methods and compositions for inactivating TCR genes, using engineered nucleases comprising at least one DNA binding domain and a cleavage domain or cleavage half-domain in conditions able to preserve cell viability. Polynucleotides encoding nucleases, vectors comprising polynucleotides encoding nucleases and cells comprising polynucleotides encoding nucleases and/or cells comprising nucleases are also provided. Disclosed herein are also methods and compositions for expressing a functional exogenous TCR in the absence of endogenous TCR expression in T lymphocytes, including lymphocytes with a central memory phenotype. Polynucleotides encoding exogenous TCR, vectors comprising polynucleotides encoding exogenous TCR and cells comprising polynucleotides encoding exogenous TCR and/or cells comprising exogenous TCR are also provided.

Targeted disruption of the T cell receptor

Disclosed herein are methods and compositions for inactivating MEW genes, using zinc finger nucleases (ZFNs) comprising a zinc finger protein and a cleavage domain or cleavage half-domain in conditions able to preserve cell viability. Polynucleotides encoding ZFNs, vectors comprising polynucleotides encoding ZFNs and cells comprising polynucleotides encoding ZFNs and/or cells comprising ZFNs are also provided.

Targeted disruption of the MHC cell receptor

Described herein are compositions and methods for modulation of gene expression in the liver including modulation of PCSK9, TTR, SERPINA1, KLKB1 and/or HAO1.

Modulation of liver genes

Liver-specific constructs and methods of use thereof

Disclosed herein are methods and compositions for inactivating MHC genes, using zinc finger nucleases (ZFNs) comprising a zinc finger protein and a cleavage domain or cleavage half-domain in conditions able to preserve cell viability. Polynucleotides encoding ZFNs, vectors comprising polynucleotides encoding ZFNs and cells comprising polynucleotides encoding ZFNs and/or cells comprising ZFNs are also provided.

The present disclosure is in the field of genome engineering, particularly targeted modification of the genome of a cell.

Delivery methods and compositions for nuclease-mediated genome engineering

Liver-specific constructs, factor VIII expression cassettes and methods of use thereof

This includes a condiment, such as mustard, catsup, etc. dispensing unit. The condiment is in a container such as a bottle with a neck portion which is attached to a novel plastic dispenser cap. When the device is hanging upside down, the condiment in the container flows into the dispensing tip which has a valve mechanism such that no fluid flows out the end of the tip until pressure is applied by squeezing the plastic tip. A push rod with two spaced apart arms has a roller at the end of each arm. The rollers are a lesser distance apart than the diameter of the dispensing nipple. When the rod pushes the arm, the rollers roll against the dispensing nipple, squeezing and compressing it, and forcing its condiments out the lower end.

Dispensing units for liquids

A dispenser comprising a condiment supply container, a squeezeable dispensing nipple, and a connector connecting the container and nipple.

Dispensing unit for a threaded neck bottle

This is a dispensing unit for condiments such as mustard, catsup, etc. or industrial liquids such as soap, chemicals. The condiment is contained in a container such as a bottle with a neck portion which is attached to a dispensing nipple. When the device is hanging upside down, the condiment in the container flows into the dispensing tip, which has a valve such that no fluid flows out the end of the tip until pressure is applied by squeezing the plastic bottle. A dispenser nipple passes through a hole in a plate or tray in a housing. A back resilient pad is on one side of the hole, and on the front side of the hole is a front pad. The dispensing nipple extends through this hole between the two pads. A push rod connects to a push plate on the front side of the front pad, and the application of force on the push rod forces the two pads towards each other. When the nipple is between them, it causes the nipple to be squeezed, thus dispensing condiment out the tip.

Push pad unit for dispensing fluids

A dispensing unit for a threaded neck bottle including a dispensing nipple, valve assembly, and a connector. The dispensing nipple is squeezable and mostly cylindrical in shape with one end converging. The bottom of the converging end is open so that the fluid contained within the dispensing nipple escapes when the nipple is squeezed. The valve arrangement is disposed inside the convergent end of the dispensing nipple and includes a rod connecting a ball valve at its bottom and a truncated cone shaped member at its other end. The connector secures the neck of the storage bottle to the dispensing nipple and includes outer and inner concentric cylinders secured to and made an integral part of an annular ring having an outside diameter and an inside diameter about the same diameter as the first and second concentric cylinders. The annular ring seals one end of the space between the cylinders. The inside of the outer cylinder is provided with threads for threadably receiving the top of the dispensing nipple into the side of the connector away from the annular ring. The inside of the inner cylinder is provided with internal threads to threadably receive the threaded neck of the storage bottle inserted from the side of the annular ring away from the concentric cylinders. The lower end of the internal concentric cylinder is provided with a seat which mates with the truncated cone shaped member within the dispensing nipple to seat when the condiment bottle is inverted.

A bottle which may be in a straight-up position for storage and in an inverted position for dispensing of condiments, such as ketchup, mayonnaise, mustard, etc. The top has a cap which may be removed and replaced by a dispensing nozzle. The bottom has two parallel ridge members and has a hole in the flat area therebetween that is closable with a tethered plug. When the bottle is ready to be used for dispensing condiments, the cap is replaced with the dispensing nozzle and the bottle is turned upside down. At this time, the tethered plug is removed so as to release pressure in the bottle so its contents may escape through the dispensing nozzle. The bottle is of shape and weight so that when inverted and hung on a stand, it will hang properly perpendicular to the ground. The bottles are also shaped so that they will nestle against one another with very little clearance. The bottle can be filled with condiments, inverted for dispensing through the dispensing nozzle, and the plug from the vent hole is removed when the bottle is hung upside down and is used. At the end of the day, the tethered plug is placed in the vent hole, and the bottles are then placed up so they can be stored in refrigeration units.

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Richmond, CA, United States of America

Gary K Lee