Other

Biosource Technologies, Inc.

Large Scale Biology Corporation

Robert L Erwin

David R McGee

David L Berliner

Monto H Kumagai

Thomas H Turpen

Laurence K Grill

Gregory P Pogue

Guy R Della-Cioppa

The invention relates to the production of enzymatically active recombinant human and animal lysosomal enzymes involving construction and expression of recombinant expression constructs comprising coding sequences of human or animal lysosomal enzymes in a plant expression system. The plant expression system provides for post-translational modification and processing to produce a recombinant gene product exhibiting enzymatic activity. The invention is demonstrated by working examples in which transgenic tobacco plants express recombinant expression constructs comprising human glucocerebrosidase nucleotide sequences. The invention is also demonstrated by working examples in which transfected tobacco plants express recombinant viral expression constructs comprising human &#x3b1; galactosidase nucleotide sequences. The recombinant lysosomal enzymes produced in accordance with the invention may be used for a variety of purposes, including but not limited to enzyme replacement therapy for the therapeutic treatment of human and animal lysosomal storage diseases.

Production of lysosomal enzymes in plants by transient expression

The present invention provides a method of compiling a plant functional gene profile, a method of changing the phenotype or biochemistry of a plant, a method of determining a change in phenotype or biochemistry of a plant, and a method of determining the presence of a trait in plant. The methods comprise expressing transiently a nucleic acid sequence of a plant into a host plant to affect phenotypic or biochemical changes in the host plant. A viral vector functional genomic screen has been developed to identify nucleotide sequences in transfected plants by systemically knocking out endogenous gene expression in an antisense mechanism. Once the presence of a trait in a plant is identified by phenotypic or biochemical changes in the host plant, the nucleic acid insert in the cDNA clone or in the vector that results in the changes is then sequenced. The present invention exemplifies that genes encoding GTP binding proteins in one plant can silence endogenous gene expression in a different plant.

Method of compiling a functional gene profile in a plant by transfecting a nucleic acid sequence of a donor plant into a different host plant in an anti-sense orientation

The invention is directed to the treatment of degenerative diseases of tissues which have lost melanin and which share a common embryological basis as tissues of the nervous system by the administration of an active substance which causes an increased concentration of melanin in the tissue. Such active substances include melanin, melanin variants, melanin analogs, melanin derivatives, tyrosinase, tyrosinase gene, melanin-concentrating hormone and combinations thereof. Examples of such diseases include Parkinson's disease, Alzheimer's disease, retinitis pigmentosa, schizophrenia and dementia. The invention is also useful in assisting in the repair of neurons in a mammal having neuron damage by administering an effective amount of an active substance which causes an increased concentration of melanin in the neuron to aid in nerve repair. The invention is further useful in protecting a mammal from a toxin-induced disease or from the adverse effects of a toxin by administering an effective amount of the active substance described above.

Therapeutic uses of melanin

The invention is directed to the treatment of degenerative diseases of tissues which have lost melanin and which share a common embryological basis as tissues of the nervous system by the administration of an active substance which causes an increased concentration of melanin in the tissue. Such active substances include melanin, melanin variants, melanin analogs, melanin derivatives, tyrosinase, tyrosinase gene, melanin-concentrating hormone and combinations thereof. Examples. of such diseases include Parkinson's disease, Alzheimer's disease, retinitis pigmentosa, schizophrenia and dementia. The invention is also useful in assisting in the repair of neurons in a mammal having neuron damage by administering an effective amount of an active substance which causes an increased concentration of melanin in the neuron to aid in nerve repair. The invention is further useful in protecting a mammal from a toxin-induced disease or from the adverse effects of a toxin by administering an effective amount of the active substance described above.

Methods of treating Parkinson's disease using melanin

A rotary, segmented, expansible valve comprising a valve body having a fluid passage and a body opening intersecting the fluid passage, a valve member rotatably mounted in the valve body opening and divided into four quarter segments, the valve member having an opening to register with the fluid passage of the valve body, the valve member opening extending through one opposed pair of the quarter segments, the other opposed pair of the quarter segments being solid and forming fluid stops when registered with the fluid passage, a tube lining the valve member opening, the one opposed pair of quarter segments being slidably mounted on the tube and sealed with respect thereto, a valve stem and handle for rotating the valve member between open and closed positions, valve seats in the valve body opening where the opening intersects the fluid passage, and an expander for selectively expanding the opposed pairs of quarter segments outwardly against the valve seats to form a fluid seal between the expanded quarter segments and the valve seats.

Rotary, segmented, expansible valves

A tapered rotary valve plug fits into a tapered valve chamber and is rotated by an operating head or cap. Cam means are provided to automatically shift the operating head and valve plug axially as the head is rotated. A pin-and-slot connection between the operating head and valve plug is provided whereby rotation of the plug is delayed until the plug has been lifted from its seat, after which rotation of the plug takes place as rotation of the head is continued. Spring means, tensioned during the initial relative rotation of the operating head and plug, are provided for restoring head and plug to their original position relative to each other as soon as the valve plug has been loosened from its seat. Means are also provided for positively stopping rotation of the plug at full open or closed positions.

Growing community of inventors

Vacaville, CA, United States of America

Robert L Erwin