Abstract: Provided is a unit dose of recombinant adeno-associated virus (AAV) particles for expression of matrix metalloproteinase 3 (MMP-3). Further provided is a unit dose of recombinant MMP-3. Also provided are methods of use thereof, e.g., in transducing the corneal endothelium of a subject; reducing intraocular pressure in an eye of a subject; treating and/or preventing elevated intraocular pressure in a subject; and treating and/or preventing glaucoma in a subject. Subjects include primates.

Abstract: The present invention is directed to compositions and methods for the treatment of degenerative retinal conditions. According to a general aspect, the present invention is directed to inflammatory mediators, preferably components or substrates of the NLRP3-inflammasome, for use in the treatment of degenerative retinal conditions involving drusen and anaphylatoxin-induced choroidal-neovascularisation. The invention is also directed to a method for the treatment of degenerative retinal conditions involving drusen and anaphylatoxin-induced choroidal-neovascularisation and to recombinant vectors and recombinant proteins for use in such methods. The present invention also provides a method for determining the risk of developing or monitoring the progression of diseases involving drusen and anaphylatoxin-induced choroidal neo-vascularisation.

Abstract: A method of using RNA interference (RNAi) for the transient, reversible and controlled opening of the tight junctions of the blood brain barrier and/or the blood retinal barrier. This method may be used in the treatment of many diseases and disorders which require the opening of the blood brain barrier and/or blood retinal barrier. Such methods generally involve the use of an RNAi-inducing agent, such as siRNA, miRNA, shRNA or an RNAi-inducing vector whose presence within a cell results in production of an siRNA or shRNA, targeting tight junction proteins to open the blood brain barrier and/or blood retinal barrier.

Abstract: The present invention is directed to an RNAi-inducing agent capable of reducing and/or inhibiting the expression of proteins associated with the tight junction complex joining Schlemm's canal endothelial cells (SCEC) in the eye of a subject for use in the prevention and/or treatment of glaucoma. Specifically, the RNAi-inducing agent is capable of reducing and/or inhibiting the expression of proteins expressed in the tight junction complex or supporting the tight junction complex joining Schlemm's canal endothelial cells (SCEC) in the eye of a subject for use in the prevention and/or treatment of glaucoma. Methods using this RNAi-inducing agent are also contemplated.

Abstract: The disclosure provides compositions and methods useful for treating glaucoma. In particular, the invention provides an adeno-associated viral (AAV)-mediated gene therapy for glaucoma in which transduced cells of the eye secrete a therapeutic protein (for example, a matrix metalloproteinase) resulting in remodeling of the extracellular matrix of the trabecular meshwork of said eye.

Abstract: The present invention is directed to compositions and methods for the treatment of degenerative retinal conditions. According to a general aspect, the present invention is directed to inflammatory mediators, preferably components or substrates of the NLRP3-inflammasome, for use in the treatment of degenerative retinal conditions involving drusen and anaphylatoxin-induced choroidal-neovascularisation. The invention is also directed to a method for the treatment of degenerative retinal conditions involving drusen and anaphylatoxin-induced choroidal-neovascularisation and to recombinant vectors and recombinant proteins for use in such methods. The present invention also provides a method for determining the risk of developing or monitoring the progression of diseases involving drusen and anaphylatoxin-induced choroidal neo-vascularisation.

Abstract: A method of using RNA interference (RNAi) for the transient, reversible and controlled opening of the tight junctions of the blood brain barrier and/or the blood retinal barrier. This method may be used in the treatment of many diseases and disorders which require the opening of the blood brain barrier and/or blood retinal barrier. Such methods generally involve the use of an RNAi-inducing agent, such as siRNA, miRNA, shRNA or an RNAi-inducing vector whose presence within a cell results in production of an siRNA or shRNA, targeting tight junction proteins to open the blood brain barrier and/or blood retinal barrier.

Abstract: The present invention is directed to a method and use of RNA interference (RNAi) for the transient, reversible and controlled opening of the tight junctions of the blood brain barrier and/or the blood retinal barrier. This method may be used in the treatment of many diseases and disorders which require the opening of the blood brain barrier and/or blood retinal barrier. Such methods generally involve the use of an RNAi-inducing agent, such as siRNA, miRNA, shRNA or an RNAi-inducing vector whose presence within a cell results in production of an siRNA or shRNA, targeting tight junction proteins to open the blood brain barrier and/or blood retinal barrier.

Abstract: The present invention is directed to compositions and methods for the treatment of degenerative retinal conditions. According to a general aspect, the present invention is directed to inflammatory mediators, preferably components or substrates of the NLRP3-inflammasome, for use in the treatment of degenerative retinal conditions involving drusen and anaphylatoxin-induced choroidal-neovascularisation. The invention is also directed to a method for the treatment of degenerative retinal conditions involving drusen and anaphylatoxin-induced choroidal-neovascularisation and to recombinant vectors and recombinant proteins for use in such methods. The present invention also provides a method for determining the risk of developing or monitoring the progression of diseases involving drusen and anaphylatoxin-induced choroidal neo-vascularisation.

Abstract: The invention relates to gene suppression and replacement. In particular, the invention relates to enhanced expression of suppression agents for suppressing gene expression in a cell and in vivo and replacement nucleic acids that are not inhibited by the suppression agent. Regulatory elements are included in expression vectors to optimize expression of the suppression agent and/or replacement nucleic acid.

Abstract: Methods and agents for suppressing expression of a mutant allele of a gene and providing a replacement nucleic acid are provided. The methods of the invention provide suppression effectors such as, for example, antisense nucleic acids, ribozymes, or RNAi, that bind to the gene or its RNA. The invention further provides for the introduction of a replacement nucleic acid with modified sequences such that the replacement nucleic acid is protected from suppression by the suppression effector. The replacement nucleic acid is modified at degenerate wobble positions in the target region of the suppression effector and thereby is not suppressed by the suppression effector. In addition, by altering wobble positions, the replacement nucleic acid can still encode a wild type gene product. The invention has the advantage that the same suppression strategy could be used to suppress, in principle, many mutations in a gene.

Abstract: The invention relates to gene suppression and replacement. In particular, the invention relates to enhanced expression of suppression agents for suppressing gene expression in a cell and in vivo and replacement nucleic acids that are not inhibited by the suppression agent. Regulatory elements are included in expression vectors to optimize expression of the suppression agent and/or replacement nucleic acid.

Abstract: The invention relates to gene suppression and replacement. In particular, the invention relates to enhanced expression of suppression agents for suppressing gene expression in a cell and in vivo and replacement nucleic acids that are not inhibited by the suppression agent. Regulatory elements are included in expression vectors to optimize expression of the suppression agent and/or replacement nucleic acid.

Abstract: The present invention relates to classical pathway complement proteins and their use in the prognosis and prevention of diseases involving cone photoreceptor degeneration. Specifically, the present invention is directed to the use of one or more classical pathway complement proteins, preferably involved in the recognition phase, in the maintenance of cone photoreceptor cell viability in a degenerating retina. The invention is also directed to a method for determining the susceptibility, risk of development and/or progression of diseases involving cone photoreceptor degeneration in a subject.

Abstract: Methods and agents for suppressing expression of a mutant allele of a gene and providing a replacement nucleic acid are provided. The methods of the invention provide suppression effectors such as, for example, antisense nucleic acids, ribozymes, or RNAi, that bind to the gene or its RNA. The invention further provides for the introduction of a replacement nucleic acid with modified sequences such that the replacement nucleic acid is protected from suppression by the suppression effector. The replacement nucleic acid is modified at degenerate wobble positions in the target region of the suppression effector and thereby is not suppressed by the suppression effector. In addition, by altering wobble positions, the replacement nucleic acid can still encode a wild type gene product. The invention has the advantage that the same suppression strategy could be used to suppress, in principle, many mutations in a gene.

Abstract: The present invention is directed to a method and use of RNA interference (RNAi) for the transient, reversible and controlled opening of the tight junctions of the blood brain barrier and/or the blood retinal barrier. This method may be used in the treatment of many diseases and disorders which require the opening of the blood brain barrier and/or blood retinal barrier. Such methods generally involve the use of an RNAi-inducing agent, such as siRNA, miRNA, shRNA or an RNAi-inducing vector whose presence within a cell results in production of an siRNA or shRNA, targeting tight junction proteins to open the blood brain barrier and/or blood retinal barrier.

Abstract: The invention relates to gene suppression and replacement. In particular, the invention relates to enhanced expression of suppression agents for suppressing gene expression in a cell and in vivo and replacement nucleic acids that are not inhibited by the suppression agent. Regulatory elements are included in expression vectors to optimize expression of the suppression agent and/or replacement nucleic acid.

Abstract: A strategy for suppressing expression of one allele of an endogenous gene is provided comprising providing suppression effectors such as antisense nucleic acids able to bind to polymorphisms within or adjacent to a gene such that one allele of a gene is exclusively or preferentially suppressed and if required of a replacement gene can be introduced. The invention has the advantage that the same suppression strategy when directed to polymorphisms could be used to suppress, in principle, many mutations in a gene. This is particularly relevant when large numbers of mutations within a single gene cause disease pathology.

Abstract: Methods and agents for suppressing expression of a mutant allele of a gene having a polymorphism are provided. The methods of the invention provide suppression effectors such as antisense nucleic acids or ribozymes, that bind to nucleic acid regions having a polymorphism within a gene such that one allele of a gene is exclusively or preferentially suppressed. The method also provides the administration of a replacement nucleic acid, if required. The invention has the advantage that the same suppression strategy, when directed to polymorphisms, could be used to suppress, in principle, many mutations in a polymorphic gene. This is particularly relevant when large numbers of mutations within a single gene cause disease pathology.

Abstract: A space based manufacturing system including a control module and a manufacturing module. The manufacturing module contains the tools required for automated processing of materials into finalized components. The control module allows command and control of the manufacturing module as well as communication with earth based systems. For component manufacture, the component requiring manufacture is identified in space, designed and engineered on earth, and manufactured in space using computer integrated manufacturing to tie these processes together. The astronaut in the control module monitors the safety of the manufacturing operation and may control manufacturing in real time.