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

Paul Kenna

Peter Humphries

Sophia Millington-Ward

Naomi Chadderton

Gwyneth Jane Farrar

Arpad Palfi

Mary O'Reilly

Gwenyth Jane Farrar

Mathew Alan Carrigan

Mary O'reilly

An isolated nucleic acid sequence encoding the yeast NDI1 protein of SEQ ID NO: 542 or a functional variant thereof is described. The nucleic acid sequence comprises at least 50 codons which are codon optimized compared with the sequence of yeast NDI1 gene of SEQ ID NO: 1.

Variants of yeast NDI1 gene, and uses thereof in the treatment of disease associated with mitochondrial dysfunction

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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Dublin, Ireland

Paul Kenna