The Provost, Fellows, Foundation Scholars, and the Other Members of Board, of the College of the Holy and Undivided Trinity of Queen Elizabeth Near Dublin

Optigen Patents Limited

Spark Therapeutics Ireland Limited

Peter Humphries

Paul Kenna

Matthew Campbell

Gwyneth Jane Farrar

Sophia Millington-Ward

Anna-Sophia Kiang

Naomi Chadderton

Arpad Palfi

Mary O'Reilly

Gwenyth Jane Farrar

Luke O'Neill

Sarah Doyle

Marian Humphries

Paul Francis Kenna

Luke O'neill

Mary O'reilly

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.

Composition and methods for the treatment of degenerative retinal conditions

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.

Method for opening tight junctions

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.

Rhodopsin gene conserved regions in a viral vector enhance expression

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. Also disclosed is a transgenic mouse that expresses human rhodopsin (modified replacement gene) and a transgenic mouse that expresses a suppression effector targeting rhodopsin. Also disclosed in intraocular administration of siRNA.

Genetic suppression and replacement

A strategy for suppressing specifically or partially specifically an endogenous gene and introducing a replacement gene, said strategy comprising the steps of:

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Peter Humphries